title: Combining adverse pregnancy and perinatal outcomes for women exposed to antiepileptic drugs during pregnancy, using a latent trait model.
abstract: Application of latent variable models in medical research are becoming increasingly popular. A latent trait model is developed to combine rare birth defect outcomes in an index of infant morbidity.
  
  
  
  This study employed four statewide, retrospective 10-year data sources (1999 to 2009). The study cohort consisted of all female Florida Medicaid enrollees who delivered a live singleton infant during study period. Drug exposure was defined as any exposure to Antiepileptic drugs (AEDs) during pregnancy. Mothers with no AED exposure served as the AED unexposed group for comparison. Four adverse outcomes, birth defect (BD), abnormal condition of new born (ACNB), low birth weight (LBW), and pregnancy and obstetrical complication (PCOC), were examined and combined using a latent trait model to generate an overall severity index. Unidimentionality, local independence, internal homogeneity, and construct validity were evaluated for the combined outcome.
  
  
  
  The study cohort consisted of 3183 mother-infant pairs in total AED group, 226 in the valproate only subgroup, and 43,956 in the AED unexposed group. Compared to AED unexposed group, the rate of BD was higher in both the total AED group (12.8% vs. 10.5%, P < .0001), and the valproate only subgroup (19.6% vs. 10.5%, P < .0001). The combined outcome was significantly correlated with the length of hospital stay during delivery in both the total AED group (Rho = 0.24, P < .0001) and the valproate only subgroup (Rho = 0.16, P = .01). The mean score for the combined outcome in the total AED group was significantly higher (2.04 ± 0.02 vs. 1.88 ± 0.01, P < .0001) than AED unexposed group, whereas the valproate only subgroup was not.
  
  
  
  Latent trait modeling can be an effective tool for combining adverse pregnancy and perinatal outcomes to assess prenatal exposure to AED, but evaluation of the selected components is essential to ensure the validity of the combined outcome.
authors.affiliation: Health Outcomes, College of Pharmacy, University of Rhode Island, 7 Greenhouse Rd., Kingston, RI, 02881, USA. xuerongwen@uri.edu.
authors.forename: Xuerong
authors.identifier: 0000-0002-4803-7895
authors.initials: X
authors.lastname: Wen
authors.affiliation: Department of Pharmaceutical Outcome and Policy, University of Florida, Gainesville, FL, USA.
authors.forename: Abraham
authors.initials: A
authors.lastname: Hartzema
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Delaney
authors.affiliation: Department of Biostatistics, University of Florida, Gainesville, FL, USA.
authors.forename: Babette
authors.initials: B
authors.lastname: Brumback
authors.affiliation: Department of Biostatistics & Epidemiology, Systems, Population and Leadership, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics & Gynecology, University of Florida, Gainesville, FL, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Egerman
authors.affiliation: Department of Pediatrics, University of Florida, Gainesville, FL, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Roth
authors.affiliation: Department of Pharmaceutical Outcome and Policy, University of Florida, Gainesville, FL, USA.
authors.forename: Rich
authors.initials: R
authors.lastname: Segal
authors.affiliation: Department of Neurology & Neurological Sciences, Stanford University, Stanford, CA, USA.
authors.forename: Kimford J
authors.initials: KJ
authors.lastname: Meador
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology / Q000209:etiology; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005431:Florida; D006801:Humans; D007230:Infant, Low Birth Weight; D063868:Patient Outcome Assessment; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000453:epidemiology; D012189:Retrospective Studies; D014635:Valproic Acid / Q000009:adverse effects*
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid
keywords: Adverse perinatal outcome; Adverse pregnancy outcome; Antiepileptic drugs; Combining outcomes; Latent trait model; Valproate