title: Antenatal exposure to sulindac and risk of necrotizing enterocolitis.
abstract: OBJECTIVE
  Most studies of tocolytics are underpowered to assess drug effects on rare adverse neonatal outcomes. Our aim was to optimize statistical power to assess the influence of sulindac on the rare but severe outcome of necrotizing enterocolitis (NEC) by performing a case-control study.
  
  
  METHODS
  A priori sample size of 78 in each group was estimated to detect a 2.5-fold increase in nonsteroidal antiinflammatory drug exposure in NEC cases. Maternal-neonatal charts were reviewed from 2007 through 2012 to yield 110 NEC cases: 68 patients with confirmed NEC by Bell's stage II criteria, and 42 with suspected NEC. Cases and controls (N = 131, matched according to gestational age at delivery, plurality, and delivery date) were compared in rates of antenatal exposures to nonsteroidal antiinflammatory drugs, other tocolytics, and maternal-neonatal characteristics and complications.
  
  
  RESULTS
  Cases and controls were delivered at a mean of 28 weeks. Approximately 52% of the total cohort received tocolytics (26% indomethacin, 15% sulindac, 32% calcium channel blockers, 32% beta-sympathomimetics), with no differences in frequency of use between cases and controls. While there was no difference in indomethacin exposure between cases and controls, antenatal exposure to sulindac was independently associated with increased risk of NEC (adjusted odds ratio, 5.33; 95% confidence interval, 1.38-20.57; P = .02), even after adjustment for other factors significantly associated with NEC.
  
  
  CONCLUSIONS
  Our data demonstrate an adverse association of sulindac with NEC. These findings deserve further investigation and using sulindac as a tocolytic agent requires caution.
authors.affiliation: Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH. Electronic address: Beena.Kamath-Rayne@cchmc.org.
authors.forename: Beena D
authors.initials: BD
authors.lastname: Kamath-Rayne
authors.affiliation: Fetal Care Center of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Good Samaritan Hospital, Cincinnati, OH.
authors.forename: Mounira
authors.initials: M
authors.lastname: Habli
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Zahidee
authors.initials: Z
authors.lastname: Rodriguez
authors.affiliation: University of Cincinnati, Cincinnati, OH.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Wu
authors.affiliation: University of Cincinnati, Cincinnati, OH.
authors.forename: James
authors.initials: J
authors.lastname: Gresh
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Cincinnati School of Medicine, Cincinnati, OH.
authors.forename: Emily A
authors.initials: EA
authors.lastname: DeFranco
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016022:Case-Control Studies; D020345:Enterocolitis, Necrotizing / Q000139:chemically induced* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D012189:Retrospective Studies; D018570:Risk Assessment; D013467:Sulindac / Q000009:adverse effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013467:Sulindac
keywords: indomethacin; necrotizing enterocolitis; nonsteroidal antiinflammatory drugs; sulindac; tocolytics