Antenatal Risk Factors Associated with Spontaneous Intestinal Perforation in Preterm Infants Receiving Postnatal Indomethacin

To determine if antenatal variables affect the risk of spontaneous intestinal perforation (SIP) among preterm infants when prophylactic indomethacin is used.Retrospective case-control study of infants29 weeks of gestational age between January 2010 and June 2018 at one hospital. SIP was defined as acute abdominal distension and pneumoperitoneum without signs of necrotizing enterocolitis at14 days of life. Each case (n = 57) was matched with 2 controls (n = 114) for gestational age and birth year. Maternal and infant data were abstracted until the SIP or equivalent day for controls. Univariate analyses were followed by adjusted conditional logistic regressions and reported as OR and 95% CI.Mothers of cases were younger, more often delivering multiples (31% vs 14%, P = .007), and less abruptions (15% vs 29%, P = .045) but did not differ in intra-partum betamethasone, magnesium, or indomethacin use. Prophylactic indomethacin was given on day 1 to 99% of infants. SIP was associated with a shorter interval from last betamethasone dose to delivery (46 hours vs 96 hours, P = .01). Dopamine use (14% vs 4%, P = .02), volume expansion (23% vs 8%, P = .003), and high grade intraventricular hemorrhage (28% vs 8%, P = .0008) were related postnatal factors. The adjusted odds of SIP increased by 1% for each hour decrease between the last dose of betamethasone and delivery (OR 1.01, 95% CI 1.002-1.019) and with multiple births (OR 2.66, 95% CI 1.05-6.77).Antenatal betamethasone given shortly before delivery is associated with an increased risk of SIP. Potential interaction with medications such as postnatal indomethacin needs study.