Early cerebral and intestinal oxygenation in the risk assessment of necrotizing enterocolitis in preterm infants

Highlights

• Tissue ischemia is hypothesized to play a putative role in the development of NEC.

• Lower cerebral oxygenation in the first 2 days after birth was associated with a higher risk for NEC in preterm infants.

• The clinical usefulness of intestinal NIRS monitoring needs to be investigated further.

Abstract

Background and aim

Predicting necrotizing enterocolitis (NEC) might help in preventing its devastating consequences. We aimed to investigate whether early cerebral and intestinal tissue oxygen saturation (rSO₂) and fractional tissue oxygen extraction (FTOE) predict the onset of NEC.

Study design

Prospective observational case-control study.

Subjects

Infants with gestational age (GA) <32 weeks were included. For every NEC case we matched two controls based on GA, birth weight (BW), and a patent ductus arteriosus.

Outcome measures

Cerebral oxygenation and intestinal oxygenation were prospectively monitored two-hours daily during the first five days after birth and once a week thereafter until five weeks after birth or until NEC developed. We used Kaplan-Meier analyses to determine the ability of near-infrared spectroscopy (NIRS) measurements, including their variability, to predict the development of NEC.

Results

We included ten infants (median (range) GA 27.1 (24.6–29.4) weeks, BW 903 (560–1630) grams) who developed NEC at median postnatal day 13 (range: 4–43 days), and 20 matched controls. Infants with cerebral rSO₂ <70% within the first 48 h after birth developed NEC significantly more often than infants with cerebral rSO₂ ≥70% (odds ratio 9.00 (95% CI 1.33–61.14). Intestinal FTOE was higher in infants who developed NEC compared to controls during the last NIRS measurement at median 2 days (range: 1–7) before NEC onset (median 0.65 vs. 0.44).

Conclusions

Cerebral oxygenation monitoring early after birth might be valuable in the risk assessment of NEC development. Additionally, our results suggest that intestinal oxygenation is impaired before the onset of clinical NEC.

Introduction

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in preterm infants, with mortality rates up to 40% [1]. Short-term and long-term disabilities occur frequently [[2], [3], [4], [5]]. Preventing development of NEC is currently considered the best strategy to minimize these devastating consequences [6]. Besides a preterm intestinal epithelium predisposed to an exaggerated inflammatory response to the present microbiome, impaired mesenteric perfusion inducing bowel hypoxia and ischemia is suggested to be one of the factors playing a role in the development of NEC [7].

Immature intestinal perfusion in newborn animals has been demonstrated, with less vasodilatory response to systemic hypoxemia, compared to older animals [8]. Local autoregulatory control of intestinal blood flow during low perfusion is only detectable weeks after term birth, making the intestines vulnerable to states of low perfusion pressure during the perinatal period [9]. Furthermore, in preterm infants it is supposed that a dysregulation between locally produced vasodilatory and vasoconstrictive compounds may result in ischemic intestine and contribute to the development of necrotizing enterocolitis [10,11].

Near-infrared spectroscopy (NIRS) measures regional tissue oxygen saturation (rSO₂) non-invasively. When peripheral arterial oxygen saturation (SpO₂) is obtained simultaneously, fractional tissue oxygen extraction (FTOE) can be calculated [12]. FTOE is thought to reflect the balance between oxygen delivery and consumption, and might therefore be used as an early indicator of inadequate tissue perfusion [12]. Using NIRS in a piglet model, it was reported that lower abdominal oxygen saturations and higher abdominal oxygen variation occurred before NEC develops [13,14]. This hypothesis is further supported by the finding that after NEC onset, there is a relation between both cerebral and intestinal ischemia (assessed using NIRS) and plasma levels of intestinal fatty acid- binding protein (marker for intestinal damage) [15].

Measuring tissue oxygenation could also be helpful for predicting the onset of NEC in preterm infants [16,17]. Patel et al. found lower mean intestinal rSO₂ (r_intSO₂) values in the first week after birth in preterm infants who later on developed NEC than in controls, although the controls were born after longer gestation and with higher birth weights [18]. Additionally, there is conflicting literature with regard to variability of abdominal oxygen levels and its association with NEC [13,19]. We previously found lower cerebral rSO₂ (r_cSO₂) after NEC onset in infants who subsequently developed complicated NEC, compared to infants with uncomplicated NEC [20]. Measurements of r_cSO₂ might provide additional information concerning the overall hemodynamic condition before NEC development.

We therefore investigated the possibility to use cerebral and intestinal tissue oxygen saturation values measured by NIRS in the first days after birth up to NEC development, to predict which high-risk infants went on to develop NEC.