Antenatal steroids alongwith postnatal indomethacin tied to intestinal perforation: study

Antenatal steroids are an essential component in management of women at risk of preterm labour in prevention of RDS, IVH and mortality. Postnatal prophylactic indomethacin has been shown to reduce severe IVH (grades 3 or 4) and patent ductus arteriosus (PDA) in preterm and extremely low birth weight neonates.

Researchers from University of Toronto,Canada found that co-exposure of antenatal steroids and prophylactic indomethacin was associated with spontaneous intestinal perforation(SIP), especially if antenatal steroids was received within 7 days before birth. The findings were published in Journal of Pediatrics.

The relationship of antenatal steroids and prophylactic indomethacin has been explored previously but the indication of indomethacin either for prophylaxis or treatment of PDA was not demarcation. Also this study aims at investigating the association between timing of steroids to SIP along with prophylactic indomethacin.

In this reterospective cohort study neonates with gestational age less than 26 weeks or birth weight less than 750gms admitted to NICU were included . Eligible 4720 neonates were first divided into 2 groups: no antenatal steroids and antenatal steroids. Based on the timing of antenatal steroids, the latter group was subdivided into a "recent" steroid group (complete or partial course of antenatal steroids <7 days before birth) and a "latent" steroid group (complete or partial course of antenatal steroids >7 days before birth). All groups were further divided into 2 subgroups based on co-exposure to prophylactic indomethacin or not. The antenatal steroid used was betamethasone 12 mg (combination of betamethasone phosphate 6 mg and betamethasone acetate 6 mg) and prophylactic indomethacin was defined as the use of indomethacin within the first 24 hours after birth for prevention of IVH and not for treatment of symptomatic PDA(dose of 0.1mg/kg/dose IV,3 doses 24 hours apart).

It was found that infants exposed to antenatal steroids at any time before birth and co-exposed to prophylactic indomethacin had higher odds of SIP than those who did not receive prophylactic indomethacin, especially if antenatal steroid was received within 7 days before birth. Infants not exposed to antenatal steroids and exposed to prophylactic indomethacin had lower odds of mortality than those who did not receive prophylactic indomethacin.

Previously in animal studies it has been observed that the loss of nitric oxide synthase (NOS) in the intestinal smooth muscle via combined inhibition of the neuronal NOS by steroids and endothelial NOS by indomethacin leads to disturbed intestinal motility and increases vulnerability of the intestine to perforation. The findings of this study may be supported by this pathophysiology.

Independently, antenatal steroids and prophylactic indomethacin have been shown to reduce the incidence of severe IVH in several randomized trials and observational studies but this synergistic effect was not demonstrated in current study.

Authors conclude-" The associations we identified may support the development and evaluation of an individualized approach for prophylactic indomethacin that is based on whether antenatal steroids was received and at what time."

Source: Kandraju H, Kanungo J, Lee KS, Daspal S, Adie MA, Dorling J, Ye XY, Lee SK, Shah PS; Canadian Neonatal Network (CNN); Canadian Preterm Birth Network (CPTBN) Investigators. Association of Co-Exposure of Antenatal Steroid and Prophylactic Indomethacin with Spontaneous Intestinal Perforation. J Pediatr. 2021 Aug;235:34-41.e1. doi: 10.1016/j.jpeds.2021.03.012.