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BMC Pregnancy and Childbirth
Published in: BMC Pregnancy and Childbirth 1/2017

Open Access 01-12-2017 | Research article

Combining adverse pregnancy and perinatal outcomes for women exposed to antiepileptic drugs during pregnancy, using a latent trait model

Authors: Xuerong Wen, Abraham Hartzema, Joseph A. Delaney, Babette Brumback, Xuefeng Liu, Robert Egerman, Jeffrey Roth, Rich Segal, Kimford J. Meador

Published in: BMC Pregnancy and Childbirth | Issue 1/2017

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.
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Literature
1.
2.
3.
Wyszynski DF, Nambisan M, Surve T, Alsdorf RM, Smith CR, Holmes LB. Increased rate of major malformations in offspring exposed to valproate during pregnancy. Neurology. 2005;64:961–5.CrossRefPubMed
4.
Mølgaard-Nielsen D, Hviid A. Newer-generation antiepileptic drugs and the risk of major birth defects. JAMA. 2011;305(19):1996–2002.CrossRefPubMed
5.
Bakker MK, Kerstjens-Frederikse WS, Buys CH, de Walle HE, de Jong-van den Berg LT. First-trimester use of paroxetine and congenital heart defects: a population-based case-control study. Birth Defects Res A Clin Mol Teratol. 2010;88(2):94–100.PubMed
6.
Davis RL, Rubanowice D, McPhillips H, Raebel MA, Andrade SE, Smith D, Platt R. HMO Research Network Center for Education, Research in Therapeutics. Risks of congenital malformations and perinatal events among infants exposed to antidepressant medications during pregnancy. Pharmacoepidemiol Drug Saf. 2007;16(10):1086–94.CrossRefPubMed
7.
McCulloch C. Joint modelling of mixed outcome types using latent variables. Stat Methods Med Res. 2008;17:53–73.CrossRefPubMed
8.
Rabe-Hesketh S, Skrondal A. Classical latent variable models for medical research. Stat Methods Med Res. 2008;17:5–32.CrossRefPubMed
9.
Rabe-Hesketh S, Skrondal A. Multilevel and Latent Variable Modeling with Composite Links and Exploded Likelihoods. Psychometrika. 2007;72(2):123–40.CrossRef
10.
Sobel ME. Measurement, Causation and local independence in latent variable models. In: Latent Variable Modeling and Applications to Causality, Lecture Notes in Statistics, Volume 120. 1997. p. 11–28.CrossRef
11.
Liu X, Roth J. Development and validation of an infant morbidity index using latent variable models. Stat Med. 2008;27(7):971–89.CrossRefPubMed
12.
Cordoba G, Schwartz L, Woloshin S, Bae H, Gotzsche C. Definition, reporting, and interpretation of composite outcomes in clinical trials: systematic review. BMJ. 2010;341:c3920.CrossRefPubMedPubMedCentral
13.
Freemantle N, Calvert M, Wood J, Eastaugh J, Griffin C. Composite outcomes in randomized trials: greater precision but with greater uncertainty? JAMA. 2003;289(19):2554–9.CrossRefPubMed
14.
O’Leary-Kelly SW, Volurka RJ. The empirical assessment of construct validity. J Oper Manag. 1998;16:387–405.CrossRef
15.
Persaud TVN, Chudley AE, Skalko RG. Basic concepts in teratology. New York: Alan R. Liss, Inc.; 1985.
16.
Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer S, Gideon PS, Hall K, Ray WA. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006;354(23):2443–51.CrossRefPubMed
17.
Costei AM, Kozer E, Ho T, Ito S, Koren G. Perinatal outcome following third trimester exposure to paroxetine. Arch Pediatr Adolesc Med. 2002;156(11):1129–32.CrossRefPubMed
18.
Cooper WO, Hernandez-Diaz S, Gideon P, Dyer SM, Hall K, Dudley J, Cevasco M, Thompson AB, Ray WA. Positive predictive value of computerized records for major congenital malformations. Pharmacoepidemiol Drug Saf. 2008;17:455–60.CrossRefPubMed
19.
Salemi JL, Tanner JP, Block S, Bailey M, Correia JA, Watkins SM, Kirby RS. The relative contribution of data sources to a birth defects registry utilizing passive multisource ascertainment methods: does a smaller birth defects case ascertainment net lead to overall or disproportionate loss? J Registry Manag. 2011;38(1):30–8.PubMed
20.
Wang Y, Sharpe-Stimac M, Cross PK, Druschel CM, Hwang SA. Improving case ascertainment of a population-based birth defects registry in New York State using hospital discharge data. Birth Defects Res A Clin Mol Teratol. 2005;73(10):663–8.CrossRefPubMed
21.
Reichman NE, Hade EM. Validation of birth certificate data. A study of women in New Jersey’s HealthStart program. Ann Epidemiol. 2001;11(3):186–93.CrossRefPubMed
22.
Roohan PJ, Josberger RE, Acar J, Dabir P, Feder HM, Gagliano PJ. Validation of birth certificate data in New York State. J Community Health. 2003;28(5):335–46.CrossRefPubMed
23.
Gore DC, Chez RA, Remmel RJ, Harahan M, Mock M, Yelverton R. Unreliable medical information on birth certificates. J Reprod Med. 2002;47(4):297–302.PubMed
24.
DiGiuseppe DL, Aron DC, Ranbom L, Harper DL, Rosenthal GE. Reliability of birth certificate data: a multi-hospital comparison to medical records information. Matern Child Health J. 2002;6(3):169–79.CrossRefPubMed
25.
Northam S, Knapp TR. The reliability and validity of birth certificates. J Obstet Gynecol Neonatal Nurs. 2006;35(1):3–12.CrossRefPubMed
26.
Horn SD, Sharkey PD, Buckle JM, et al. The relationship between severity of illness and hospital length of stay and mortality. Med Care. 1991;29:305–17.CrossRefPubMed
27.
Hogan DP, Park JM. Family factors and social support in the developmental outcomes of very low-birth weight children. Clin Perinatol. 2000;27:433–59.CrossRefPubMed
28.
Duong HT, Hoyt AT, Carmichael SL, Gilboa SM, Canfield MA, Case A, McNeese ML, Waller DK, and the National Birth Defects Prevention Study. Is maternal parity an independent risk factor for birth defects? Birth Defects Res A Clin Mol Teratol. 2012;94(4):230–6.
29.
Baardman ME, Kerstjens-Frederikse WS, Corpeleijn E, de Walle HE, Hofstra RM, Berger RM, Bakker MK. Combined adverse effects of maternal smoking and high body mass index on heart development in offspring: evidence for interaction? Heart. 2012;98(6):474–9. Epub 2012 Jan 30.CrossRefPubMed
30.
Siega-Riz AM, Herring AH, Olshan AF, Smith J. Moore C; National Birth Defects Prevention Study. The joint effects of maternal prepregnancy body mass index and age on the risk of gastroschisis. Paediatr Perinat Epidemiol. 2009;23(1):51–7.CrossRefPubMed
31.
Andrade SE, Raebel MA. Use of prescription medications with a potential for fetal harm among pregnant women. Pharmacoepidemiol Drug Saf. 2006;15(8);546–54.
32.
33.
Bracken MB, Holford TR. Exposure to prescribed drugs in pregnancy and association with congenital malformations. Obstet Gynecol. 1981;58(3):336–44.PubMed
34.
Davis RL, Rubanowice D, McPhillips H. HMO Research Network Center for Education, Research in Therapeutics. Risk of congenital malformations and perinatal events among infants exposed to antidepressant medications during pregnancy. Pharmacoepidemiol Drug Saf. 2007;16:1086–94.CrossRefPubMed
35.
36.
37.
38.
39.
Bartholomew DJ, Knott M. Latent variable models and factor analysis. London: Arnold; 1999.
40.
Hartley HO. The modified Gauss-Newton method for the fitting of non-linear regression functions by least squares. Techmetrics. 1961;3:269–80.CrossRef
41.
Yen WM. Scaling performance assessments: Strategies for managing local item dependence. J Educ Meas. 1993;30:187–213.CrossRef
42.
Kimberlin C, Winterstein AG. Validity and reliability of measurement instruments use in research. Am J Health-Syst Pharm. 2008;65:2276–84.CrossRefPubMed
43.
John OP, Benet-Martinez V. Measurement: Reliability, construct validation, and scale construction. In: Reis HT, Judd CM, editors. Handbook of research methods in social psychology. New York: Cambridge University Press; 2000. p. 339–69.
44.
45.
Campbell E, Kennedy F, Russell A, Smithson WH, Parsons L, Morrison PJ, Liggan B, Irwin B, Delanty N, Hunt SJ, Craig J, Morrow J. Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers. J Neurol Neurosurg Psychiatry. 2014;85(9):1029–34. doi:10.​1136/​jnnp-2013-306318.
46.
Kaneko S, Kondo T. Antiepileptic agents and birth defects: incidence, mechanisms and prevention. CNS Drugs. 1995;3(1):41–55.CrossRef
47.
48.
Samren EB, van Duijn CM, Christianens GC, et al. Antiepileptic drug regimens and major congenital abnormalities in the offspring. Ann Neurol. 1999;46:739–46.CrossRefPubMed
49.
Kaneko S, Battino D, Andermann E, et al. Congenital malformations due to antiepileptic drugs. Epilepsy Res. 1999;33:145–58.CrossRefPubMed
50.
Kaneko S, Otani K, Fukushima Y, et al. Teratogenicity of antiepileptic drugs: analysis of possible risk factors. Epilpesia. 1988;29:459–67.CrossRef
Metadata
Title
Combining adverse pregnancy and perinatal outcomes for women exposed to antiepileptic drugs during pregnancy, using a latent trait model
Authors
Xuerong Wen
Abraham Hartzema
Joseph A. Delaney
Babette Brumback
Xuefeng Liu
Robert Egerman
Jeffrey Roth
Rich Segal
Kimford J. Meador
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Pregnancy and Childbirth / Issue 1/2017
Electronic ISSN: 1471-2393
DOI
https://doi.org/10.1186/s12884-016-1190-7

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