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Arnautovic TI, Longo JL, Trail-Burns EJ, Tucker R, Keszler M, Laptook AR. Antenatal Risk Factors Associated with Spontaneous Intestinal Perforation in Preterm Infants Receiving Post-natal Indomethacin. J Pediatr. 2021 Jan 13:S0022-3476(21)00015-9. doi: 10.1016/j.jpeds.2021.01.011. Epub ahead of print. PMID: 33453204.

Objective: To determine if antenatal variables affect the risk of spontaneous intestinal perforation (SIP) among preterm infants when prophylactic indomethacin is used.

Study design: Retrospective case-control study of infants <29 weeks gestational age (GA) between January 2010 and June 2018 at one hospital. SIP was defined as acute abdominal distension and pneumoperitoneum without signs of necrotizing enterocolitis at <14 days of life. Each case (n=57) was matched with two controls (n= 114) for GA 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 odds ratio and 95% confidence interval (CI).

Results: Mothers of cases were younger, more often delivering multiples (31% vs 14%, P = .007), and less abruptions (15% vs 29%, p=0.045) 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 (46h vs 96h, p=0.01). Dopamine use (14% vs 4% p=0.02), volume expansion (23% vs 8%, p=0.003), and high grade IVH (28% vs 8%, p=0.0008) 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).

Conclusions: Antenatal betamethasone given shortly before delivery is associated with an increased risk of SIP. Potential interaction with medications such as post-natal indomethacin needs study.

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