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but is also a good marker of iodine intake and status&#44; as the low concentration of iodine in the neonatal thyroid gland requires higher rates of iodine turnover&#44; so that TSH levels increase if the iodine supply is low<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a>&#46; Based on the recommendations of the WHO&#44; a prevalence of less than 3&#37; of neonatal TSH levels greater than 5 mIU&#47;L is indicative of iodine sufficiency in a population<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46; However&#44; numerous obstetric and neonatal factors can influence neonatal TSH levels besides maternal iodine status<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The main aim of our study was to determine the prevalence of neonatal TSH levels greater than 5 mIU&#47;L in our catchment area&#46; A secondary objective was to assess the impact of maternal iodine intake&#44; UIC and thyroid on neonatal TSH levels&#46; Lastly&#44; we analysed other obstetric and neonatal factors that could be associated with neonatal TSH levels&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study population</span><p id="par0025" class="elsevierStylePara elsevierViewall">We conducted a longitudinal&#44; observational&#44; descriptive and analytic study in pregnant women and neonates in the hospital&#8217;s catchment area&#44; with a population of 330&#44;560 inhabitants&#46; Overall&#44; iodine status in this region is adequate&#44; both in the general population<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> and in pregnant women<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Participants were selected out of the total of pregnant women who attended the initial visit with the midwife between May and June 2017&#46; The applied inclusion and exclusion criteria can be seen in the flow chart of the study &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The study was approved by the Regional Research Ethics Committee&#46; All participants signed the informed consent form&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Study variables</span><p id="par0040" class="elsevierStylePara elsevierViewall">In the first visit with the midwife&#44; a questionnaire was administered to assess iodine intake&#44; collecting information on the regular consumption of iodized salt &#40;yes&#47;no&#41; and dairy products &#40;daily servings of milk&#44; yoghurt and cheese&#41;&#44; and use of iodine supplementation &#40;yes&#47;no&#41;&#46; The results of the iodine intake survey were published by Gonz&#225;lez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Urinary iodine concentration&#44; thyroid function and antithyroid-antibody tests were performed in the first trimester of gestation&#44; the results of which were published by Gonz&#225;lez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#44; and we also collected neonatal TSH levels&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The maternal UIC was measured in a random urine sample by inductively coupled plasma mass spectrometry &#40;ICP-MS&#41; with an Agilent 7700&#215; spectrometer &#40;Agilent Technologies&#44; Santa Clara&#44; CA&#44; USA&#46;&#41;&#46; This method exhibited an adequate linearity between 10 and 450&#160;&#956;g&#47;L &#40;R<span class="elsevierStyleSup">2</span>&#160;&#62;&#160;0&#46;99&#41;&#44; with an intralaboratory imprecision of 2&#46;9&#37; or less and a total analytical error of 7&#46;3&#37; or less&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">In the same visit&#44; the mother underwent collection of a blood sample for measurement of TSH levels and anti-thyroid antibody testing &#40;thyroid peroxidase antibodies &#91;TPOAb&#93; and thyroglobulin antibodies &#91;TgAb&#93;&#41;&#46; The measurements were made by electrochemiluminescence immunoassay &#40;Roche Diagnostics&#44; Basel&#44; Switzerland&#41;&#46; The coefficient of variation &#40;CV&#41; for TSH values ranged from 0&#46;8&#37; to 2&#46;9&#37;&#46; In our catchment area&#44; the normal range for TSH levels was 0&#46;20&#8211;4&#46;50 mIU&#47;L&#46; The normal range for autoantibodies was less than 34 UI&#47;mL for TPOAb and less than 18 UI&#47;mL for TgAb&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Newborns underwent heel lancing&#44; preferably between 48 and 72h post birth&#44; for collection of capillary blood collected in a Whatman&#174; 903 paper card &#40;dried blood spot&#41; in the framework of the congenital hypothyroidism screening programme&#46; Neonatal TSH was measured by dissociation-enhanced lanthanide fluorescent immunoassay &#40;DELFIA&#41; in the clinical biochemistry laboratory of our hospital&#46; We considered neonatal TSH levels of less than 10 mIU&#47;L normal&#46; If the value was between 10 and 20 mIU&#47;L&#44; a second measurement was made&#44; and in the case of a TSH level greater than 20 mIU&#47;L&#44; the patient was referred to the neonatal unit&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Lastly&#44; we collected data on the birth weight and gestational age of the newborn&#44; mode of delivery &#40;uncomplicated &#91;not requiring intervention by physician&#47;midwife&#93;&#44; operative vaginal delivery or caesarean section&#41;&#44; reason for operative vaginal or caesarean delivery&#44; presence of nonreassuring foetal status &#40;NRFS&#41; and 1-min Apgar score &#40;Apgar-1&#41;&#46; The presence of NRFS was determined by the obstetrician if there were any signs or symptoms suggestive of hypoxic metabolic acidosis&#44; including severe clinical conditions and abnormalities in the different diagnostic methods used to assess foetal wellbeing&#44; such as cardiotocography&#44; pulse oximetry&#44; pH measurement or Doppler ultrasound&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0070" class="elsevierStylePara elsevierViewall">We conducted a descriptive analysis&#44; calculating absolute and relative frequency distributions for qualitative variables and measures of central tendency and dispersion for quantitative variables&#46; We assessed differences in numerical variables by means of the Student <span class="elsevierStyleItalic">t</span>-test or Wilcoxon test for independent samples based on whether the homogeneity of variance assumption was met&#46; To compare three or more variables&#44; we used analysis of variance &#40;ANOVA&#41; or the Kruskal-Wallis test&#44; based on whether the normality and homoscedasticity assumptions were met&#46; We assessed the association between two variables by means of the &#967;<span class="elsevierStyleSup">2</span> test or Fisher exact test based on the expected counts&#46; We used the McNemar test in the case of paired proportions&#46; We fitted 2 multivariate binary logistic regression models to predict neonatal levels of TSH greater than 5 mIU&#47;L&#44; calculating odds ratios &#40;OR&#41;&#44; 95&#37; confidence intervals &#40;CIs&#41; and <span class="elsevierStyleItalic">P</span> values for the Wald test&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">We entered the data in an ACCESS-SQL 2010 database&#46; The statistical analysis was performed with the software R &#40;R Development Core Team&#41;&#44; version 36&#46;0&#46; We defined statistical significance as a <span class="elsevierStyleItalic">P</span> value of 005&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0080" class="elsevierStylePara elsevierViewall">We selected 332 pregnant women&#44; of who 14 were not eligible because they met 1 or more of the exclusion criteria&#46; Other patients did not complete the study due to miscarriage &#40;&#160;&#61;&#160;<span class="elsevierStyleItalic">n</span> 47&#41;&#44; diagnosis of gestational hypothyroidism &#40;<span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;17&#41; or being lost to follow-up &#40;<span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;11&#41;&#46; Ultimately&#44; we collected data for 243 mother-child dyads&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Out of all neonates&#44; 124 were male&#46; The mean gestational age was 39&#46;8 weeks &#40;standard deviation &#91;SD&#93;&#44; 1&#46;6&#41;&#44; and 13 infants were born preterm &#40;&#60;37 weeks of gestation&#41;&#46; The mean birth weight was 3260&#160;&#177;&#160;517&#46;5&#160;g&#44; and 16 neonates had birth weights of less than 2500&#160;g&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Neonatal TSH levels</span><p id="par0090" class="elsevierStylePara elsevierViewall">Neonatal TSH levels were measured in samples collected between 48 and 72h post birth in 90&#46;4&#37; of newborns &#40;95th percentile &#91;P95&#93;&#44; 72h&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The mean neonatal TSH level was 2&#46;43 mIU&#47;L &#40;SD&#44; 1&#46;68&#41;&#46; The 5th to 95th percentile range was 0&#46;60&#8211;6&#46;60 mIU&#47;L&#44; while the first to 99th percentile range was 0&#46;25&#8211;8&#46;60 mIU&#47;L&#46; All newborns had TSH levels in the normal range&#44; and 7&#46;8&#37; had levels greater than 5 mIU&#47;L&#46; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> presents the distribution of neonatal TSH levels&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">We analysed neonatal TSH values based on the timing of sample collection&#46; The mean TSH value in samples collected within 48h of birth was 3&#46;36 mIU&#47;L &#40;SD&#44; 1&#46;83 mIU&#47;L&#41;&#44; significantly higher compared to samples collected between 48 and 72h &#40;mean&#44; 2&#46;44 mIU&#47;L&#59; SD&#44; 1&#46;69&#41; or 72h post birth &#40;1&#46;79 mIU&#47;L&#59; SD&#44; 1&#46;80 mIU&#47;L&#41; &#40;<span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;020&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Maternal factors&#58; iodine intake&#44; ioduria and thyroid function</span><p id="par0105" class="elsevierStylePara elsevierViewall">We analysed the association between iodine intake &#40;iodized salt&#44; dairy products and iodine supplements&#41; and neonatal TSH levels&#44; and found no statistically significant differences&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">To analyse the association between neonatal TSH and maternal UIC in the first trimester of gestation&#44; we grouped newborns based on whether their mothers had an insufficient &#40;&#60;150&#160;&#956;g&#47;L&#41;&#44; adequate &#40;150&#8722;250&#160;&#956;g&#47;L&#41;&#44; greater than adequate &#40;250&#8722;500&#160;&#956;g&#47;L&#41; or excessive &#40;&#62;500&#160;&#956;g&#47;L&#41; concentration of iodine in urine&#46; The results were statistically significant &#40;<span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;021&#41; and are presented in <a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">We calculated the proportion of infants with neonatal TSH levels greater than 5 mIU&#47;L based on the maternal UIC&#44; and found statistically significant differences &#40;<span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;014&#41;&#46; The proportion of infants with TSH values greater than 5 mIU&#47;L was 11&#46;9&#37; in the insufficient maternal UIC group compared to 8&#46;3&#37; in the adequate maternal UIC group&#46; All infants born to mothers with an UIC greater than 250&#160;&#956;g&#47;L had neonatal TSH values of less than 5 mIU&#47;L&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The analysis of the association of neonatal TSH values and maternal thyroid function was limited to the cases for which antithyroid-antibody test results were available &#40;<span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;128&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarises these results&#46; We found that the mean neonatal TSH level was significantly lower in infants born to mothers with TSH values of less than 2&#46;50 mIU&#47;L&#44; independently of thyroid autoantibody status&#44; although the differences were more marked in the subset with mothers who tested positive for thyroid autoantibodies&#46; All infants born to mothers with TSH levels of less than 2&#46;50 and negative thyroid autoantibody test results had neonatal TSH levels of 5 mIU&#47;L or less&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Obstetric and neonatal factors</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Type of delivery</span><p id="par0125" class="elsevierStylePara elsevierViewall">Fifty-six percent of infants were born by uncomplicated vaginal delivery&#44; 28&#46;4&#37; by caesarean delivery and 15&#46;6&#37; by operative vaginal delivery&#46; The mean neonatal TSH level was 2&#46;04 mIU&#47;L &#40;SD&#44; 1&#46;52&#41; in the uncomplicated delivery group&#44; 3&#46;04 mIU&#47;L &#40;SD&#44; 1&#46;79&#41; in the caesarean delivery group and 2&#46;88 mIU&#47;L &#40;SD&#44; 1&#46;72&#41; in the operative vaginal delivery group &#40;<span class="elsevierStyleItalic">P</span>&#160;&#60;&#160;0&#46;001&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">In the uncomplicated delivery group&#44; 4&#46;4&#37; of infants had neonatal TSH levels greater than 5 mIU&#47;L&#44; compared to 7&#46;9&#37; in the caesarean delivery group and 14&#46;5&#37; in the operative vaginal delivery group &#40;<span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;039&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Birth weight and gestational age</span><p id="par0135" class="elsevierStylePara elsevierViewall">We compared neonatal TSH levels in infants with birthweights of less than 2500&#160;g and infants with birthweights of 2500&#160;g and greater&#44; and found no significant differences &#40;mean&#160;&#177;&#160;SD&#44; 2&#46;73&#160;&#177;&#160;2&#46;71 mIU&#47;L vs 2&#46;41&#160;&#177;&#160;1&#46;59 mIU&#47;L&#59; <span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;345&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">We also compared neonatal TSH levels in infants born before and after 37 weeks&#8217; gestation&#44; and also found no significant differences &#40;mean&#160;&#177;&#160;SD&#44; 3&#46;34&#160;&#177;&#160;3&#46;17 mIU&#47;L vs 2&#46;40&#160;&#177;&#160;1&#46;60 mIU&#47;L&#59; <span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;224&#41;&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Probability of nonreassuring foetal status</span><p id="par0145" class="elsevierStylePara elsevierViewall">Nonreassuring foetal status was documented in 24&#46;7&#37; of newborns&#46; The proportion of NRFS was 31&#46;2&#37; in infants with birthweights of less than 2500&#160;g compared to 19&#46;8&#37; in those with birthweights of 2500&#160;g or greater&#46; Also&#44; NRFS occurred in 23&#46;1&#37; of infants born before 37 weeks compared to 24&#46;8&#37; of those born at 37 weeks or after&#46; Nonreassuring foetal status was the most frequent reason for caesarean delivery &#40;41&#46;5&#37; of total cases&#41; and operative vaginal delivery &#40;64&#46;2&#37; of total cases&#41;&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">We compared neonatal TSH levels in infants with a history of NRFS to neonatal TSH levels in infants born by caesarean section or instrumental delivery without NRFS and infants born by uncomplicated vaginal delivery&#46; The mean neonatal TSH values in these groups were 3&#46;22 mIU&#47;L &#40;SD&#44; 1&#46;84&#41;&#44; 2&#46;67 mIU&#47;L &#40;SD&#44; 1&#46;75&#41; and 2&#46;02 mIU&#47;L &#40;SD&#44; 1&#46;52&#41;&#44; respectively &#40;<span class="elsevierStyleItalic">P</span>&#160;&#60;&#160;0&#46;001&#41;&#46; Fifteen percent of infants born by caesarean section or operative vaginal delivery due to NRFS had neonatal TSH levels greater than 5 mIU&#47;L compared to 10&#46;4&#37; of infants born by caesarean section or operative vaginal delivery without NRFS and 4&#46;3&#37; of infants with an uncomplicated vaginal birth &#40;<span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;026&#41;&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">1-min APGAR</span><p id="par0155" class="elsevierStylePara elsevierViewall">The 1-min Apgar score was less than 9 points in 20&#46;2&#37; of the infants&#46; The neonatal TSH levels in these patients were greater compared to those with 1-min Apgar scores of 9 or more points &#40;mean&#160;&#177;&#160;SD&#44; 2&#46;80&#160;&#177;&#160;1&#46;84 mIU&#47;L vs 2&#46;34&#160;&#177;&#160;1&#46;63 mIU&#47;L&#41;&#44; although the difference was not statistically significant &#40;<span class="elsevierStyleItalic">P</span>&#160;&#61;&#160; &#46;087&#41;&#46; Of the infants with 1-min Apgar scores of less than 9 points&#44; 16&#46;3&#37; had neonatal TSH levels greater than 5 mIU&#47;L compared to 5&#46;7&#37; of infants with 1-min Apgar scores of 9 points or greater &#40;<span class="elsevierStyleItalic">P</span>&#160;&#61;&#160; &#46;031&#41;&#46; The mean 1-min Apgar score in newborns with neonatal TSH levels of 5 mIU&#47;L or lower was greater compared to newborns with TSH levels greater than 5 mIU&#47;L &#40;mean &#177; SD&#44; 8&#46;80 &#177; 0&#46;91 points vs 7&#46;84 &#177; 1&#46;74 points&#59; <span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;002&#41;&#46;</p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Multivariate analysis</span><p id="par0160" class="elsevierStylePara elsevierViewall">We conducted a univariate analysis and fitted 2 multivariate binary logistic regression models &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The dependent variable in both models was a neonatal TSH level greater than 5 mIU&#47;L&#46; In Model 1&#44; the included variables were maternal UIC&#44; thyroid function and iodine intake&#46; This initial analysis showed that a maternal UIC greater than 150&#160;&#956;g&#47;L was a risk factor for a neonatal TSH level greater than 5 mIU&#47;L &#40;OR&#44; 3&#46;27&#59; 95&#37; CI&#44; 1&#46;03&#8722;11&#46;55&#59; <span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;049&#41;&#46; In Model 2&#44; in addition to these variables&#44; we included the mode of delivery&#44; birth weight&#44; gestational age&#44; presence of NRFS and 1-min Apgar score&#46; In this model&#44; a maternal UIC greater than 150 &#956;g&#47;L remained a risk factor for a neonatal TSH level greater than 5 mIU&#47;L &#40;OR&#44; 3&#46;70&#59; 95&#37; CI&#44; 1&#46;06&#8722;14&#46;60&#59; <span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;046&#41;&#44; while a birthweight of 2500 g or greater was a protective factor &#40;OR&#44; 0&#46;14&#59; 95&#37; CI&#44; 0&#46;02&#8722;1&#46;00&#59; <span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;038&#41;&#46; A 1-min Apgar score of less than 9 points behaved as a protective factor against neonatal TSH levels greater than 5 mIU&#47;L&#44; with a <span class="elsevierStyleItalic">P</span> value that neared the threshold of significance&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Discussion</span><p id="par0165" class="elsevierStylePara elsevierViewall">In our study&#44; the mean neonatal TSH level was 2&#46;43 mIU&#47;L&#44; and none of the newborns had TSH levels greater than 10 mIU&#47;L&#46; The proportion of newborns with TSH values greater than 5 mIU&#47;L was 7&#46;8&#37;&#46; The WHO has proposed that a frequency of 3&#37; or greater of neonatal TSH levels over 5 mIU&#47;L is indicative of iodine insufficiency in the population<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#44; a criterion that has since been validated by Zimmermann et al&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#46; However&#44; pregnant women in our study exhibited an adequate iodine status<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> and the general population in our area is also iodine sufficient<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">The main factor that may explain a high prevalence of neonatal TSH levels greater than 5 mIU&#47;L in an iodine-sufficient population is the time elapsed from birth to collection of the blood sample&#46; The foetal thyroid starts to synthesise hormones from 18 to 20 weeks of gestation<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46; From that point&#44; TSH levels increase progressively&#44; peaking 30&#8722;60&#160;min post birth at values of up to 60&#8211;100 mIU&#47;L&#44; followed by a marked drop in the next 48&#160;h and eventual stabilization by 3&#8211;5 days post birth<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a>&#46; The WHO recommends measurement of neonatal TSH levels in dried blood spots with collection of sample from 72h post birth<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46; However&#44; in our study&#44; as is the case of many other recent ones&#44; samples were collected in the framework of newborn screening for congenital hypothyroidism between 48 and 72h post birth&#46; Our findings corroborate that neonatal TSH levels continue to decline past 72h post birth&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Measuring neonatal TSH levels is the most sensitive method to identify congenital hypothyroidism<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#44; but these values may be affected by several factors<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a>&#46; One is the maternal iodine status&#46; The foetal thyroid is very sensitive to iodine deficiency&#44; but also to its excess&#46; When iodine levels are excessive&#44; the foetal thyroid is not sufficiently mature to escape the inhibitory Wolff-Chaikoff effect until 36 weeks&#8217;gestation<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a>&#46; This is reflected by multiple studies in which excessive iodine intake in the mother was found to be associated with congenital hypothyroidism<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> or the use of iodine-containing antiseptics during childbirth was found to induce transient hypothyroidism in neonates<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">In our study&#44; we did not find a significant association between neonatal TSH levels and maternal iodine intake&#44; but we found an association with the maternal UIC in the first trimester of the pregnancy&#46; The offspring of mothers with sufficient UICs did not have neonatal TSH levels greater than 5 mIU&#47;L and&#44; overall&#44; neonatal TSH levels were higher the lower the maternal UIC&#46; Both multivariate models showed that maternal iodine deficiency is a risk factor for neonatal TSH levels greater than 5 mIU&#47;L&#44; corroborating the association between maternal iodine status and neonatal TSH levels&#46; The results of previous studies have been heterogeneous&#44; with some confirming<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a> and others finding no evidence<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a> of this association&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Another factor that may have an impact on neonatal TSH levels is maternal thyroid function<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;24</span></a>&#46; In our study&#44; we found that infants born to mothers with TSH levels of less than 2&#46;50 mIU&#47;L had significantly lower neonatal TSH levels compared to infants born to mothers with TSH levels above that threshold&#44; with more marked differences in the case of mothers who were positive for thyroid autoantibodies&#46; In addition&#44; all infants born to mothers with TSH levels under TSH &#60;2&#46;5 mIU&#47;L and negative for thyroid autoantibodies had neonatal TSH levels of 5 mIU&#47;L or less&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">In addition to being influenced by the iodine status or thyroid function of the mother&#44; neonatal TSH levels may be affected by multiple maternal&#44; neonatal or obstetric factors resulting in foetal stress<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;25</span></a>&#46; The mode of delivery&#44; preterm birth or low birth weight for gestational age are some of these factors&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Caesarean delivery is associated with lower neonatal TSH levels compared to operative or uncomplicated vaginal delivery<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;26</span></a>&#46; These differences can be explained by the increased catecholamine levels associated with vaginal delivery<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;14</span></a>&#46; Still&#44; there have also been studies that have not found any differences based on the mode of delivery<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;27</span></a> and others in which the highest neonatal TSH levels were found in infants delivered by caesarean section<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;29</span></a>&#46; In our study&#44; infants delivered by caesarean section had the highest neonatal TSH levels&#44; although the multivariate analysis did not find an association between mode of delivery and neonatal TSH levels&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Congenital hypothyroidism is more frequent in preterm or low birth weight newborns due to the immaturity of the hypothalamic-pituitary axis<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a>&#46; Preterm infants may experience transient hypothyroxinaemia in the first weeks of life&#44; with a delayed postnatal TSH peak that usually takes place 2&#8211;6 weeks post birth<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;31</span></a>&#46; Low birth weight is also an independent factor that may influence neonatal TSH levels<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;32</span></a>&#46; In our study&#44; a birth weight greater than 2500&#160;g was associated with a lower probability of neonatal TSH levels greater than 5 mIU&#47;L&#44; although we did not find an association with gestational age&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Lastly&#44; we analysed 2 factors that are direct indicators of foetal stress&#44; such as nonreassuring foetal status and the 1-min Apgar score&#46; Neither of these factors was significantly associated with TSH levels in our study&#44; but Korevaar et al&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> found that factors related to foetal stress&#44; such as respiratory distress&#44; were associated with transient abnormalities in neonatal thyroid function&#46; Along the same lines&#44; other studies have found an association between foetal distress<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> or low Apgar scores<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> and abnormal thyroid function in the neonatal period&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">The main limitation of our study was the sample size which&#44; while large enough to assess the primary outcomes&#44; was too small to yield statistically significant results in some of the analyses&#46; Another limitation was the retrospective data collection&#44; as there could have been confounding factors at play that were not taken into account and interfered with the results&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">In conclusion&#44; the prevalence of neonatal levels of TSH greater than 5 mIU&#47;L in our catchment area was high based on the recommendations of the WHO&#44; in spite of being a population with an adequate iodine status&#46; Neonatal TSH levels are a good marker of iodine nutritional status&#44; as demonstrated by their correlation with maternal urinary iodine concentrations in the first trimester of gestation&#44; and maternal iodine deficiency was associated with an increased risk of neonatal TSH levels greater than 5 mIU&#47;L&#46; However&#44; since neonatal TSH levels are currently measured within 72h of birth in the context of screening for congenital hypothyroidism&#44; new cut-off points need to be established to continue using this parameter as a marker of iodine status&#44; which requires performance of additional studies&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflicts of interest</span><p id="par0220" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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              "titulo" => "Maternal factors&#58; iodine intake&#44; ioduria and thyroid function"
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            1 => "Concentraci&#243;n urinaria de yodo"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Neonatal thyroid stimulating hormone &#40;nTSH&#41; is a marker of iodine nutrition status in the population&#46; The WHO considers a prevalence of less than 3&#37; of nTSH levels greater than 5 mIU&#47;L in samples obtained within 72h from birth indicative of iodine sufficiency&#46; The aim of this study was to determine the prevalence of nTSH levels greater than 5 mIU&#47;L in an iodine-sufficient population and its association with maternal&#44; neonatal and obstetric factors&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Materials and methods</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">A total of 243 pregnant women were recruited between May and June 2017 in our health area&#46; A questionnaire of iodine intake was administered&#44; in addition to determination of ioduria&#44; thyroid function and autoimmunity in the first trimester of gestation&#46; We analysed nTSH levels in samples collected between 48 and 72h post birth and other obstetric and neonatal factors&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">The mean nTSH level &#40;standard deviation&#41; was 2&#46;43 &#40;1&#46;68 mIU&#47;L&#41;&#44; with 7&#46;8&#37; of neonates having levels greater than 5 mIU&#47;L&#46; The highest nTSH levels corresponded to neonates of mothers with insufficient ioduria &#40;<span class="elsevierStyleItalic">P</span> &#61; 0&#46;021&#41; or TSH levels greater than 2&#46;5 mIU&#47;L&#44; in both the case of negative &#40;<span class="elsevierStyleItalic">P</span> &#61; 0&#46;049&#41; and positive &#40;<span class="elsevierStyleItalic">P</span> &#61; 0&#46;006&#41; thyroid autoimmunity results&#46; Maternal ioduria less than 150&#160;&#956;g&#47;L was a risk factor for nTSH levels greater than 5 mIU&#47;L &#40;3&#46;70 &#91;1&#46;06&#8722;14&#46;60&#93;&#59; <span class="elsevierStyleItalic">P</span> &#61; 0&#46;046&#41;&#44; while a neonatal weight of 2500&#160;g or greater was a protective factor &#40;0&#46;14 &#91;0&#46;02&#8722;1&#46;00&#93;&#59; <span class="elsevierStyleItalic">P</span> &#61; 0&#46;038&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">The prevalence of nTSH levels greater than 5 mIU&#47;L in our health area was high based on the WHO recommendations&#46; Maternal iodine deficiency was associated with a higher risk of nTSH levels greater than 5 mIU&#47;L&#46; Given that nTSH is currently measured before 72h post birth&#44; we need new cut-off points to keep on using nTSH as a marker of iodine nutritional status&#46;</p></span>"
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            "titulo" => "Introduction"
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            "titulo" => "Materials and methods"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">La TSH neonatal &#40;TSHn&#41; es un marcador de nutrici&#243;n de yodo en la poblaci&#243;n&#46; La OMS relaciona una prevalencia &#60;3&#37; de TSHn &#62;5 mUI&#47;L&#44; obtenidas a partir de las 72h del nacimiento&#44; con un adecuado estado nutricional de yodo&#46; El objetivo de este estudio es conocer la prevalencia de TSHn &#62;5 mUI&#47;L en una poblaci&#243;n yodosuficiente y su relaci&#243;n con factores maternos&#44; neonatales y obst&#233;tricos&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Materiales y m&#233;todos</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Se reclutaron 243 gestantes entre mayo y junio de 2017 en nuestra &#225;rea sanitaria&#46; Se realiz&#243; un cuestionario sobre consumo de yodo y determinaci&#243;n de yoduria&#44; funci&#243;n y autoinmunidad tiroideas en el primer trimestre de gestaci&#243;n&#46; Se analiz&#243; la TSHn entre 48&#8722;72h del nacimiento&#44; as&#237; como otros factores obst&#233;tricos y neonatales&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Resultados</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">La TSHn media fue 2&#44;43&#160;&#177;&#160;1&#44;68 mUI&#47;L&#44; con 7&#44;8&#37; de neonatos con TSHn &#62;5 mUI&#47;L&#46; La TSHn m&#225;s elevada pertenec&#237;a a los neonatos de madres con yodurias insuficientes &#40;p&#160;&#61;&#160;0&#46;021&#41; o con TSH&#160;&#62;&#160;2&#46;5 mUI&#47;L&#44; tanto en autoinmunidad tiroidea negativa &#40;p&#160;&#61;&#160;0&#44;049&#41; como positiva &#40;p&#160;&#61;&#160;0&#44;006&#41;&#46; La yoduria materna &#60;150&#160;&#956;g&#47;L fue un factor de riesgo de TSHn &#62;5 mUI&#47;L &#40;3&#44;70 &#91;1&#44;06-14&#44;60&#93;&#44; p&#160;&#61;&#160;0&#44;046&#41;&#44; mientras el peso neonatal &#8805;2500&#160;gr fue un factor protector &#40;0&#44;14 &#91;0&#44;02-1&#44;00&#93;&#44; p&#160;&#61;&#160;0&#44;038&#41;&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusiones</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">La prevalencia de TSHn &#62;5 mUI&#47;L en nuestra &#225;rea sanitaria fue elevada&#44; seg&#250;n las recomendaciones de la OMS&#46; Se asoci&#243; el d&#233;ficit de yodo materno con mayor riesgo de TSHn &#62;5 mUI&#47;L&#46; Dado que en la actualidad la determinaci&#243;n de la TSHn se realiza antes de las 72h del nacimiento&#44; precisamos de nuevos puntos de corte para continuar empleando la TSHn como marcador de nutrici&#243;n de yodo&#46;</p></span>"
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                  """
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                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="7" align="left" valign="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;15&#8722;5&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;758&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">UIC &#40;&#956;g&#47;L&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8805;150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;18&#8722;8&#46;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;024&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;03&#8722;11&#46;55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;049&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">TSH &#40;mIU&#47;L&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;2&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8805;2&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;31&#8722;2&#46;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;835&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;26&#8722;3&#46;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;995&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Model 2</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Iodized salt</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;29&#8722;2&#46;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;723&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;42&#8722;5&#46;58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;548&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Dairy products</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;2 servings&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8805;2 servings&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;30&#8722;2&#46;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;767&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;19&#8722;2&#46;82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;690&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Iodine supplement</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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Original Article
Neonatal TSH as a marker of iodine nutrition status. Effect of maternal ioduria and thyroid function on neonatal TSH
TSH neonatal como marcador del estado de nutrición de yodo. Influencia de la yoduria y la función tiroidea maternas sobre la TSH neonatal
Silvia González Martíneza,b,
Corresponding author
silvia@endohuca.com

Corresponding author.
, Belén Prieto Garcíac, Ana Isabel Escudero Gomisd, Elías Delgado Álvareza,b,e, Edelmiro Luis Menéndez Torrea,b,e
a Servicio de Endocrinología y Nutrición, Hospital Universitario Central de Asturias, Oviedo, Spain
b Grupo de investigación en Endocrinología, Nutrición, Diabetes y Obesidad (ENDO), Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Spain
c Servicio de Bioquímica Clínica, Hospital Universitario Central de Asturias, Oviedo, Spain
d Servicio de Obstetricia y Ginecología, Hospital Universitario Central de Asturias, Oviedo, Spain
e Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Iodine is an essential trace element for the synthesis of thyroid hormones&#46; In adults&#44; iodine deficiency is associated with thyroid dysfunction and goitre&#44; and in pregnant women&#44; with increases in the frequency of miscarriage&#44; perinatal mortality and congenital anomalies in the offspring<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#44; which in turn is associated with abnormal growth and neurodevelopment<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46; Iodine deficiency continues to be the leading cause of preventable neurologic impairment<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46; The World Health Organization &#40;WHO&#41; recommends universal salt iodization and the use of iodine supplements in at-risk groups&#44; in addition to periodic performance of surveys to monitor iodine status at the population level<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Measurement of the urinary iodine concentration &#40;UIC&#41; in school-age children is the most widely used method to assess population iodine status<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46; However&#44; other markers are also available&#44; such as neonatal thyroid stimulating hormone &#40;TSH&#41; levels<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;6&#44;7</span></a>&#44; the prevalence of goitre in school-age children<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> or thyroglobulin serum levels<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Neonatal TSH levels are used to screen congenital hypothyroidism in newborns&#44; but is also a good marker of iodine intake and status&#44; as the low concentration of iodine in the neonatal thyroid gland requires higher rates of iodine turnover&#44; so that TSH levels increase if the iodine supply is low<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a>&#46; Based on the recommendations of the WHO&#44; a prevalence of less than 3&#37; of neonatal TSH levels greater than 5 mIU&#47;L is indicative of iodine sufficiency in a population<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46; However&#44; numerous obstetric and neonatal factors can influence neonatal TSH levels besides maternal iodine status<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The main aim of our study was to determine the prevalence of neonatal TSH levels greater than 5 mIU&#47;L in our catchment area&#46; A secondary objective was to assess the impact of maternal iodine intake&#44; UIC and thyroid on neonatal TSH levels&#46; Lastly&#44; we analysed other obstetric and neonatal factors that could be associated with neonatal TSH levels&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study population</span><p id="par0025" class="elsevierStylePara elsevierViewall">We conducted a longitudinal&#44; observational&#44; descriptive and analytic study in pregnant women and neonates in the hospital&#8217;s catchment area&#44; with a population of 330&#44;560 inhabitants&#46; Overall&#44; iodine status in this region is adequate&#44; both in the general population<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> and in pregnant women<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Participants were selected out of the total of pregnant women who attended the initial visit with the midwife between May and June 2017&#46; The applied inclusion and exclusion criteria can be seen in the flow chart of the study &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The study was approved by the Regional Research Ethics Committee&#46; All participants signed the informed consent form&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Study variables</span><p id="par0040" class="elsevierStylePara elsevierViewall">In the first visit with the midwife&#44; a questionnaire was administered to assess iodine intake&#44; collecting information on the regular consumption of iodized salt &#40;yes&#47;no&#41; and dairy products &#40;daily servings of milk&#44; yoghurt and cheese&#41;&#44; and use of iodine supplementation &#40;yes&#47;no&#41;&#46; The results of the iodine intake survey were published by Gonz&#225;lez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Urinary iodine concentration&#44; thyroid function and antithyroid-antibody tests were performed in the first trimester of gestation&#44; the results of which were published by Gonz&#225;lez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#44; and we also collected neonatal TSH levels&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The maternal UIC was measured in a random urine sample by inductively coupled plasma mass spectrometry &#40;ICP-MS&#41; with an Agilent 7700&#215; spectrometer &#40;Agilent Technologies&#44; Santa Clara&#44; CA&#44; USA&#46;&#41;&#46; This method exhibited an adequate linearity between 10 and 450&#160;&#956;g&#47;L &#40;R<span class="elsevierStyleSup">2</span>&#160;&#62;&#160;0&#46;99&#41;&#44; with an intralaboratory imprecision of 2&#46;9&#37; or less and a total analytical error of 7&#46;3&#37; or less&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">In the same visit&#44; the mother underwent collection of a blood sample for measurement of TSH levels and anti-thyroid antibody testing &#40;thyroid peroxidase antibodies &#91;TPOAb&#93; and thyroglobulin antibodies &#91;TgAb&#93;&#41;&#46; The measurements were made by electrochemiluminescence immunoassay &#40;Roche Diagnostics&#44; Basel&#44; Switzerland&#41;&#46; The coefficient of variation &#40;CV&#41; for TSH values ranged from 0&#46;8&#37; to 2&#46;9&#37;&#46; In our catchment area&#44; the normal range for TSH levels was 0&#46;20&#8211;4&#46;50 mIU&#47;L&#46; The normal range for autoantibodies was less than 34 UI&#47;mL for TPOAb and less than 18 UI&#47;mL for TgAb&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Newborns underwent heel lancing&#44; preferably between 48 and 72h post birth&#44; for collection of capillary blood collected in a Whatman&#174; 903 paper card &#40;dried blood spot&#41; in the framework of the congenital hypothyroidism screening programme&#46; Neonatal TSH was measured by dissociation-enhanced lanthanide fluorescent immunoassay &#40;DELFIA&#41; in the clinical biochemistry laboratory of our hospital&#46; We considered neonatal TSH levels of less than 10 mIU&#47;L normal&#46; If the value was between 10 and 20 mIU&#47;L&#44; a second measurement was made&#44; and in the case of a TSH level greater than 20 mIU&#47;L&#44; the patient was referred to the neonatal unit&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Lastly&#44; we collected data on the birth weight and gestational age of the newborn&#44; mode of delivery &#40;uncomplicated &#91;not requiring intervention by physician&#47;midwife&#93;&#44; operative vaginal delivery or caesarean section&#41;&#44; reason for operative vaginal or caesarean delivery&#44; presence of nonreassuring foetal status &#40;NRFS&#41; and 1-min Apgar score &#40;Apgar-1&#41;&#46; The presence of NRFS was determined by the obstetrician if there were any signs or symptoms suggestive of hypoxic metabolic acidosis&#44; including severe clinical conditions and abnormalities in the different diagnostic methods used to assess foetal wellbeing&#44; such as cardiotocography&#44; pulse oximetry&#44; pH measurement or Doppler ultrasound&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0070" class="elsevierStylePara elsevierViewall">We conducted a descriptive analysis&#44; calculating absolute and relative frequency distributions for qualitative variables and measures of central tendency and dispersion for quantitative variables&#46; We assessed differences in numerical variables by means of the Student <span class="elsevierStyleItalic">t</span>-test or Wilcoxon test for independent samples based on whether the homogeneity of variance assumption was met&#46; To compare three or more variables&#44; we used analysis of variance &#40;ANOVA&#41; or the Kruskal-Wallis test&#44; based on whether the normality and homoscedasticity assumptions were met&#46; We assessed the association between two variables by means of the &#967;<span class="elsevierStyleSup">2</span> test or Fisher exact test based on the expected counts&#46; We used the McNemar test in the case of paired proportions&#46; We fitted 2 multivariate binary logistic regression models to predict neonatal levels of TSH greater than 5 mIU&#47;L&#44; calculating odds ratios &#40;OR&#41;&#44; 95&#37; confidence intervals &#40;CIs&#41; and <span class="elsevierStyleItalic">P</span> values for the Wald test&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">We entered the data in an ACCESS-SQL 2010 database&#46; The statistical analysis was performed with the software R &#40;R Development Core Team&#41;&#44; version 36&#46;0&#46; We defined statistical significance as a <span class="elsevierStyleItalic">P</span> value of 005&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0080" class="elsevierStylePara elsevierViewall">We selected 332 pregnant women&#44; of who 14 were not eligible because they met 1 or more of the exclusion criteria&#46; Other patients did not complete the study due to miscarriage &#40;&#160;&#61;&#160;<span class="elsevierStyleItalic">n</span> 47&#41;&#44; diagnosis of gestational hypothyroidism &#40;<span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;17&#41; or being lost to follow-up &#40;<span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;11&#41;&#46; Ultimately&#44; we collected data for 243 mother-child dyads&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Out of all neonates&#44; 124 were male&#46; The mean gestational age was 39&#46;8 weeks &#40;standard deviation &#91;SD&#93;&#44; 1&#46;6&#41;&#44; and 13 infants were born preterm &#40;&#60;37 weeks of gestation&#41;&#46; The mean birth weight was 3260&#160;&#177;&#160;517&#46;5&#160;g&#44; and 16 neonates had birth weights of less than 2500&#160;g&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Neonatal TSH levels</span><p id="par0090" class="elsevierStylePara elsevierViewall">Neonatal TSH levels were measured in samples collected between 48 and 72h post birth in 90&#46;4&#37; of newborns &#40;95th percentile &#91;P95&#93;&#44; 72h&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The mean neonatal TSH level was 2&#46;43 mIU&#47;L &#40;SD&#44; 1&#46;68&#41;&#46; The 5th to 95th percentile range was 0&#46;60&#8211;6&#46;60 mIU&#47;L&#44; while the first to 99th percentile range was 0&#46;25&#8211;8&#46;60 mIU&#47;L&#46; All newborns had TSH levels in the normal range&#44; and 7&#46;8&#37; had levels greater than 5 mIU&#47;L&#46; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> presents the distribution of neonatal TSH levels&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">We analysed neonatal TSH values based on the timing of sample collection&#46; The mean TSH value in samples collected within 48h of birth was 3&#46;36 mIU&#47;L &#40;SD&#44; 1&#46;83 mIU&#47;L&#41;&#44; significantly higher compared to samples collected between 48 and 72h &#40;mean&#44; 2&#46;44 mIU&#47;L&#59; SD&#44; 1&#46;69&#41; or 72h post birth &#40;1&#46;79 mIU&#47;L&#59; SD&#44; 1&#46;80 mIU&#47;L&#41; &#40;<span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;020&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Maternal factors&#58; iodine intake&#44; ioduria and thyroid function</span><p id="par0105" class="elsevierStylePara elsevierViewall">We analysed the association between iodine intake &#40;iodized salt&#44; dairy products and iodine supplements&#41; and neonatal TSH levels&#44; and found no statistically significant differences&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">To analyse the association between neonatal TSH and maternal UIC in the first trimester of gestation&#44; we grouped newborns based on whether their mothers had an insufficient &#40;&#60;150&#160;&#956;g&#47;L&#41;&#44; adequate &#40;150&#8722;250&#160;&#956;g&#47;L&#41;&#44; greater than adequate &#40;250&#8722;500&#160;&#956;g&#47;L&#41; or excessive &#40;&#62;500&#160;&#956;g&#47;L&#41; concentration of iodine in urine&#46; The results were statistically significant &#40;<span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;021&#41; and are presented in <a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">We calculated the proportion of infants with neonatal TSH levels greater than 5 mIU&#47;L based on the maternal UIC&#44; and found statistically significant differences &#40;<span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;014&#41;&#46; The proportion of infants with TSH values greater than 5 mIU&#47;L was 11&#46;9&#37; in the insufficient maternal UIC group compared to 8&#46;3&#37; in the adequate maternal UIC group&#46; All infants born to mothers with an UIC greater than 250&#160;&#956;g&#47;L had neonatal TSH values of less than 5 mIU&#47;L&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The analysis of the association of neonatal TSH values and maternal thyroid function was limited to the cases for which antithyroid-antibody test results were available &#40;<span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;128&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarises these results&#46; We found that the mean neonatal TSH level was significantly lower in infants born to mothers with TSH values of less than 2&#46;50 mIU&#47;L&#44; independently of thyroid autoantibody status&#44; although the differences were more marked in the subset with mothers who tested positive for thyroid autoantibodies&#46; All infants born to mothers with TSH levels of less than 2&#46;50 and negative thyroid autoantibody test results had neonatal TSH levels of 5 mIU&#47;L or less&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Obstetric and neonatal factors</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Type of delivery</span><p id="par0125" class="elsevierStylePara elsevierViewall">Fifty-six percent of infants were born by uncomplicated vaginal delivery&#44; 28&#46;4&#37; by caesarean delivery and 15&#46;6&#37; by operative vaginal delivery&#46; The mean neonatal TSH level was 2&#46;04 mIU&#47;L &#40;SD&#44; 1&#46;52&#41; in the uncomplicated delivery group&#44; 3&#46;04 mIU&#47;L &#40;SD&#44; 1&#46;79&#41; in the caesarean delivery group and 2&#46;88 mIU&#47;L &#40;SD&#44; 1&#46;72&#41; in the operative vaginal delivery group &#40;<span class="elsevierStyleItalic">P</span>&#160;&#60;&#160;0&#46;001&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">In the uncomplicated delivery group&#44; 4&#46;4&#37; of infants had neonatal TSH levels greater than 5 mIU&#47;L&#44; compared to 7&#46;9&#37; in the caesarean delivery group and 14&#46;5&#37; in the operative vaginal delivery group &#40;<span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;039&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Birth weight and gestational age</span><p id="par0135" class="elsevierStylePara elsevierViewall">We compared neonatal TSH levels in infants with birthweights of less than 2500&#160;g and infants with birthweights of 2500&#160;g and greater&#44; and found no significant differences &#40;mean&#160;&#177;&#160;SD&#44; 2&#46;73&#160;&#177;&#160;2&#46;71 mIU&#47;L vs 2&#46;41&#160;&#177;&#160;1&#46;59 mIU&#47;L&#59; <span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;345&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">We also compared neonatal TSH levels in infants born before and after 37 weeks&#8217; gestation&#44; and also found no significant differences &#40;mean&#160;&#177;&#160;SD&#44; 3&#46;34&#160;&#177;&#160;3&#46;17 mIU&#47;L vs 2&#46;40&#160;&#177;&#160;1&#46;60 mIU&#47;L&#59; <span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;224&#41;&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Probability of nonreassuring foetal status</span><p id="par0145" class="elsevierStylePara elsevierViewall">Nonreassuring foetal status was documented in 24&#46;7&#37; of newborns&#46; The proportion of NRFS was 31&#46;2&#37; in infants with birthweights of less than 2500&#160;g compared to 19&#46;8&#37; in those with birthweights of 2500&#160;g or greater&#46; Also&#44; NRFS occurred in 23&#46;1&#37; of infants born before 37 weeks compared to 24&#46;8&#37; of those born at 37 weeks or after&#46; Nonreassuring foetal status was the most frequent reason for caesarean delivery &#40;41&#46;5&#37; of total cases&#41; and operative vaginal delivery &#40;64&#46;2&#37; of total cases&#41;&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">We compared neonatal TSH levels in infants with a history of NRFS to neonatal TSH levels in infants born by caesarean section or instrumental delivery without NRFS and infants born by uncomplicated vaginal delivery&#46; The mean neonatal TSH values in these groups were 3&#46;22 mIU&#47;L &#40;SD&#44; 1&#46;84&#41;&#44; 2&#46;67 mIU&#47;L &#40;SD&#44; 1&#46;75&#41; and 2&#46;02 mIU&#47;L &#40;SD&#44; 1&#46;52&#41;&#44; respectively &#40;<span class="elsevierStyleItalic">P</span>&#160;&#60;&#160;0&#46;001&#41;&#46; Fifteen percent of infants born by caesarean section or operative vaginal delivery due to NRFS had neonatal TSH levels greater than 5 mIU&#47;L compared to 10&#46;4&#37; of infants born by caesarean section or operative vaginal delivery without NRFS and 4&#46;3&#37; of infants with an uncomplicated vaginal birth &#40;<span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;026&#41;&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">1-min APGAR</span><p id="par0155" class="elsevierStylePara elsevierViewall">The 1-min Apgar score was less than 9 points in 20&#46;2&#37; of the infants&#46; The neonatal TSH levels in these patients were greater compared to those with 1-min Apgar scores of 9 or more points &#40;mean&#160;&#177;&#160;SD&#44; 2&#46;80&#160;&#177;&#160;1&#46;84 mIU&#47;L vs 2&#46;34&#160;&#177;&#160;1&#46;63 mIU&#47;L&#41;&#44; although the difference was not statistically significant &#40;<span class="elsevierStyleItalic">P</span>&#160;&#61;&#160; &#46;087&#41;&#46; Of the infants with 1-min Apgar scores of less than 9 points&#44; 16&#46;3&#37; had neonatal TSH levels greater than 5 mIU&#47;L compared to 5&#46;7&#37; of infants with 1-min Apgar scores of 9 points or greater &#40;<span class="elsevierStyleItalic">P</span>&#160;&#61;&#160; &#46;031&#41;&#46; The mean 1-min Apgar score in newborns with neonatal TSH levels of 5 mIU&#47;L or lower was greater compared to newborns with TSH levels greater than 5 mIU&#47;L &#40;mean &#177; SD&#44; 8&#46;80 &#177; 0&#46;91 points vs 7&#46;84 &#177; 1&#46;74 points&#59; <span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;002&#41;&#46;</p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Multivariate analysis</span><p id="par0160" class="elsevierStylePara elsevierViewall">We conducted a univariate analysis and fitted 2 multivariate binary logistic regression models &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The dependent variable in both models was a neonatal TSH level greater than 5 mIU&#47;L&#46; In Model 1&#44; the included variables were maternal UIC&#44; thyroid function and iodine intake&#46; This initial analysis showed that a maternal UIC greater than 150&#160;&#956;g&#47;L was a risk factor for a neonatal TSH level greater than 5 mIU&#47;L &#40;OR&#44; 3&#46;27&#59; 95&#37; CI&#44; 1&#46;03&#8722;11&#46;55&#59; <span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;049&#41;&#46; In Model 2&#44; in addition to these variables&#44; we included the mode of delivery&#44; birth weight&#44; gestational age&#44; presence of NRFS and 1-min Apgar score&#46; In this model&#44; a maternal UIC greater than 150 &#956;g&#47;L remained a risk factor for a neonatal TSH level greater than 5 mIU&#47;L &#40;OR&#44; 3&#46;70&#59; 95&#37; CI&#44; 1&#46;06&#8722;14&#46;60&#59; <span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;046&#41;&#44; while a birthweight of 2500 g or greater was a protective factor &#40;OR&#44; 0&#46;14&#59; 95&#37; CI&#44; 0&#46;02&#8722;1&#46;00&#59; <span class="elsevierStyleItalic">P</span>&#160;&#61;&#160;0&#46;038&#41;&#46; A 1-min Apgar score of less than 9 points behaved as a protective factor against neonatal TSH levels greater than 5 mIU&#47;L&#44; with a <span class="elsevierStyleItalic">P</span> value that neared the threshold of significance&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Discussion</span><p id="par0165" class="elsevierStylePara elsevierViewall">In our study&#44; the mean neonatal TSH level was 2&#46;43 mIU&#47;L&#44; and none of the newborns had TSH levels greater than 10 mIU&#47;L&#46; The proportion of newborns with TSH values greater than 5 mIU&#47;L was 7&#46;8&#37;&#46; The WHO has proposed that a frequency of 3&#37; or greater of neonatal TSH levels over 5 mIU&#47;L is indicative of iodine insufficiency in the population<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#44; a criterion that has since been validated by Zimmermann et al&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#46; However&#44; pregnant women in our study exhibited an adequate iodine status<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> and the general population in our area is also iodine sufficient<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">The main factor that may explain a high prevalence of neonatal TSH levels greater than 5 mIU&#47;L in an iodine-sufficient population is the time elapsed from birth to collection of the blood sample&#46; The foetal thyroid starts to synthesise hormones from 18 to 20 weeks of gestation<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46; From that point&#44; TSH levels increase progressively&#44; peaking 30&#8722;60&#160;min post birth at values of up to 60&#8211;100 mIU&#47;L&#44; followed by a marked drop in the next 48&#160;h and eventual stabilization by 3&#8211;5 days post birth<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a>&#46; The WHO recommends measurement of neonatal TSH levels in dried blood spots with collection of sample from 72h post birth<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46; However&#44; in our study&#44; as is the case of many other recent ones&#44; samples were collected in the framework of newborn screening for congenital hypothyroidism between 48 and 72h post birth&#46; Our findings corroborate that neonatal TSH levels continue to decline past 72h post birth&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Measuring neonatal TSH levels is the most sensitive method to identify congenital hypothyroidism<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#44; but these values may be affected by several factors<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a>&#46; One is the maternal iodine status&#46; The foetal thyroid is very sensitive to iodine deficiency&#44; but also to its excess&#46; When iodine levels are excessive&#44; the foetal thyroid is not sufficiently mature to escape the inhibitory Wolff-Chaikoff effect until 36 weeks&#8217;gestation<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a>&#46; This is reflected by multiple studies in which excessive iodine intake in the mother was found to be associated with congenital hypothyroidism<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> or the use of iodine-containing antiseptics during childbirth was found to induce transient hypothyroidism in neonates<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">In our study&#44; we did not find a significant association between neonatal TSH levels and maternal iodine intake&#44; but we found an association with the maternal UIC in the first trimester of the pregnancy&#46; The offspring of mothers with sufficient UICs did not have neonatal TSH levels greater than 5 mIU&#47;L and&#44; overall&#44; neonatal TSH levels were higher the lower the maternal UIC&#46; Both multivariate models showed that maternal iodine deficiency is a risk factor for neonatal TSH levels greater than 5 mIU&#47;L&#44; corroborating the association between maternal iodine status and neonatal TSH levels&#46; The results of previous studies have been heterogeneous&#44; with some confirming<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a> and others finding no evidence<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a> of this association&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Another factor that may have an impact on neonatal TSH levels is maternal thyroid function<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;24</span></a>&#46; In our study&#44; we found that infants born to mothers with TSH levels of less than 2&#46;50 mIU&#47;L had significantly lower neonatal TSH levels compared to infants born to mothers with TSH levels above that threshold&#44; with more marked differences in the case of mothers who were positive for thyroid autoantibodies&#46; In addition&#44; all infants born to mothers with TSH levels under TSH &#60;2&#46;5 mIU&#47;L and negative for thyroid autoantibodies had neonatal TSH levels of 5 mIU&#47;L or less&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">In addition to being influenced by the iodine status or thyroid function of the mother&#44; neonatal TSH levels may be affected by multiple maternal&#44; neonatal or obstetric factors resulting in foetal stress<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;25</span></a>&#46; The mode of delivery&#44; preterm birth or low birth weight for gestational age are some of these factors&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Caesarean delivery is associated with lower neonatal TSH levels compared to operative or uncomplicated vaginal delivery<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;26</span></a>&#46; These differences can be explained by the increased catecholamine levels associated with vaginal delivery<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;14</span></a>&#46; Still&#44; there have also been studies that have not found any differences based on the mode of delivery<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;27</span></a> and others in which the highest neonatal TSH levels were found in infants delivered by caesarean section<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;29</span></a>&#46; In our study&#44; infants delivered by caesarean section had the highest neonatal TSH levels&#44; although the multivariate analysis did not find an association between mode of delivery and neonatal TSH levels&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Congenital hypothyroidism is more frequent in preterm or low birth weight newborns due to the immaturity of the hypothalamic-pituitary axis<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a>&#46; Preterm infants may experience transient hypothyroxinaemia in the first weeks of life&#44; with a delayed postnatal TSH peak that usually takes place 2&#8211;6 weeks post birth<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;31</span></a>&#46; Low birth weight is also an independent factor that may influence neonatal TSH levels<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;32</span></a>&#46; In our study&#44; a birth weight greater than 2500&#160;g was associated with a lower probability of neonatal TSH levels greater than 5 mIU&#47;L&#44; although we did not find an association with gestational age&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Lastly&#44; we analysed 2 factors that are direct indicators of foetal stress&#44; such as nonreassuring foetal status and the 1-min Apgar score&#46; Neither of these factors was significantly associated with TSH levels in our study&#44; but Korevaar et al&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> found that factors related to foetal stress&#44; such as respiratory distress&#44; were associated with transient abnormalities in neonatal thyroid function&#46; Along the same lines&#44; other studies have found an association between foetal distress<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> or low Apgar scores<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> and abnormal thyroid function in the neonatal period&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">The main limitation of our study was the sample size which&#44; while large enough to assess the primary outcomes&#44; was too small to yield statistically significant results in some of the analyses&#46; Another limitation was the retrospective data collection&#44; as there could have been confounding factors at play that were not taken into account and interfered with the results&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">In conclusion&#44; the prevalence of neonatal levels of TSH greater than 5 mIU&#47;L in our catchment area was high based on the recommendations of the WHO&#44; in spite of being a population with an adequate iodine status&#46; Neonatal TSH levels are a good marker of iodine nutritional status&#44; as demonstrated by their correlation with maternal urinary iodine concentrations in the first trimester of gestation&#44; and maternal iodine deficiency was associated with an increased risk of neonatal TSH levels greater than 5 mIU&#47;L&#46; However&#44; since neonatal TSH levels are currently measured within 72h of birth in the context of screening for congenital hypothyroidism&#44; new cut-off points need to be established to continue using this parameter as a marker of iodine status&#44; which requires performance of additional studies&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflicts of interest</span><p id="par0220" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Neonatal thyroid stimulating hormone &#40;nTSH&#41; is a marker of iodine nutrition status in the population&#46; The WHO considers a prevalence of less than 3&#37; of nTSH levels greater than 5 mIU&#47;L in samples obtained within 72h from birth indicative of iodine sufficiency&#46; The aim of this study was to determine the prevalence of nTSH levels greater than 5 mIU&#47;L in an iodine-sufficient population and its association with maternal&#44; neonatal and obstetric factors&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Materials and methods</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">A total of 243 pregnant women were recruited between May and June 2017 in our health area&#46; A questionnaire of iodine intake was administered&#44; in addition to determination of ioduria&#44; thyroid function and autoimmunity in the first trimester of gestation&#46; We analysed nTSH levels in samples collected between 48 and 72h post birth and other obstetric and neonatal factors&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">The mean nTSH level &#40;standard deviation&#41; was 2&#46;43 &#40;1&#46;68 mIU&#47;L&#41;&#44; with 7&#46;8&#37; of neonates having levels greater than 5 mIU&#47;L&#46; The highest nTSH levels corresponded to neonates of mothers with insufficient ioduria &#40;<span class="elsevierStyleItalic">P</span> &#61; 0&#46;021&#41; or TSH levels greater than 2&#46;5 mIU&#47;L&#44; in both the case of negative &#40;<span class="elsevierStyleItalic">P</span> &#61; 0&#46;049&#41; and positive &#40;<span class="elsevierStyleItalic">P</span> &#61; 0&#46;006&#41; thyroid autoimmunity results&#46; Maternal ioduria less than 150&#160;&#956;g&#47;L was a risk factor for nTSH levels greater than 5 mIU&#47;L &#40;3&#46;70 &#91;1&#46;06&#8722;14&#46;60&#93;&#59; <span class="elsevierStyleItalic">P</span> &#61; 0&#46;046&#41;&#44; while a neonatal weight of 2500&#160;g or greater was a protective factor &#40;0&#46;14 &#91;0&#46;02&#8722;1&#46;00&#93;&#59; <span class="elsevierStyleItalic">P</span> &#61; 0&#46;038&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">The prevalence of nTSH levels greater than 5 mIU&#47;L in our health area was high based on the WHO recommendations&#46; Maternal iodine deficiency was associated with a higher risk of nTSH levels greater than 5 mIU&#47;L&#46; Given that nTSH is currently measured before 72h post birth&#44; we need new cut-off points to keep on using nTSH as a marker of iodine nutritional status&#46;</p></span>"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">La TSH neonatal &#40;TSHn&#41; es un marcador de nutrici&#243;n de yodo en la poblaci&#243;n&#46; La OMS relaciona una prevalencia &#60;3&#37; de TSHn &#62;5 mUI&#47;L&#44; obtenidas a partir de las 72h del nacimiento&#44; con un adecuado estado nutricional de yodo&#46; El objetivo de este estudio es conocer la prevalencia de TSHn &#62;5 mUI&#47;L en una poblaci&#243;n yodosuficiente y su relaci&#243;n con factores maternos&#44; neonatales y obst&#233;tricos&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Materiales y m&#233;todos</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Se reclutaron 243 gestantes entre mayo y junio de 2017 en nuestra &#225;rea sanitaria&#46; Se realiz&#243; un cuestionario sobre consumo de yodo y determinaci&#243;n de yoduria&#44; funci&#243;n y autoinmunidad tiroideas en el primer trimestre de gestaci&#243;n&#46; Se analiz&#243; la TSHn entre 48&#8722;72h del nacimiento&#44; as&#237; como otros factores obst&#233;tricos y neonatales&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Resultados</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">La TSHn media fue 2&#44;43&#160;&#177;&#160;1&#44;68 mUI&#47;L&#44; con 7&#44;8&#37; de neonatos con TSHn &#62;5 mUI&#47;L&#46; La TSHn m&#225;s elevada pertenec&#237;a a los neonatos de madres con yodurias insuficientes &#40;p&#160;&#61;&#160;0&#46;021&#41; o con TSH&#160;&#62;&#160;2&#46;5 mUI&#47;L&#44; tanto en autoinmunidad tiroidea negativa &#40;p&#160;&#61;&#160;0&#44;049&#41; como positiva &#40;p&#160;&#61;&#160;0&#44;006&#41;&#46; La yoduria materna &#60;150&#160;&#956;g&#47;L fue un factor de riesgo de TSHn &#62;5 mUI&#47;L &#40;3&#44;70 &#91;1&#44;06-14&#44;60&#93;&#44; p&#160;&#61;&#160;0&#44;046&#41;&#44; mientras el peso neonatal &#8805;2500&#160;gr fue un factor protector &#40;0&#44;14 &#91;0&#44;02-1&#44;00&#93;&#44; p&#160;&#61;&#160;0&#44;038&#41;&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusiones</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">La prevalencia de TSHn &#62;5 mUI&#47;L en nuestra &#225;rea sanitaria fue elevada&#44; seg&#250;n las recomendaciones de la OMS&#46; Se asoci&#243; el d&#233;ficit de yodo materno con mayor riesgo de TSHn &#62;5 mUI&#47;L&#46; Dado que en la actualidad la determinaci&#243;n de la TSHn se realiza antes de las 72h del nacimiento&#44; precisamos de nuevos puntos de corte para continuar empleando la TSHn como marcador de nutrici&#243;n de yodo&#46;</p></span>"
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">2&#46;78&#160;&#177;&#160;1&#46;92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">Positive thyroid autoantibodies</td><td class="td" title="\n
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                  <table border="0" frame="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Univariate analysis</th><th class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="7" align="left" valign="\n
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                  \t\t\t\t">0&#46;29&#8722;2&#46;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;723&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;42&#8722;4&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;655&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Dairy products</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;2 servings&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8805;2 servings&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;30&#8722;2&#46;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;767&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;22&#8722;2&#46;62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;718&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Iodine supplement</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;24&#8722;6&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;913&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;15&#8722;5&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;758&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">UIC &#40;&#956;g&#47;L&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8805;150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;18&#8722;8&#46;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;024&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;03&#8722;11&#46;55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;049&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">TSH &#40;mIU&#47;L&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;2&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8805;2&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;31&#8722;2&#46;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;835&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;26&#8722;3&#46;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;995&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Model 2</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Iodized salt</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Caesarean&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;21&#8722;12&#46;21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;527&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Operative vaginal&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#46;67&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;30&#8722;11&#46;24&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&#46;76&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;78&#8722;18&#46;43&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;093&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Peso neonatal &#40;g&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;2500&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8805;2500&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;33&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Gestational age &#40;weeks&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;37&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8805;37&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#46;03&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">1-min Apgar &#40;points&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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