Challenges in Studying Modifiable Risk Factors for Birth Defects

Tinker, Sarah C.; Gilboa, Suzanne M.; Reefhuis, Jennita; Jenkins, Mary M.; Schaeffer, Marcy L.; Moore, Cynthia A.

doi:10.1007/s40471-014-0028-y

Cited by 41 publications

(52 citation statements)

References 86 publications

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“…When possible, it is important to assess specific birth defects, rather than large heterogeneous groupings, because teratogens rarely increase risk for all congenital malformations and associations with specific defects can be obscured. (Tinker et al, ) An additional strength of NBDPS data is rigorous clinical review of birth defect cases, (Rasmussen et al, ) which decreases the chance for outcome misclassification that can occur when case definitions use only diagnosis codes, as might occur in administrative healthcare databases.…”

Section: Discussionmentioning

confidence: 99%

Use of benzodiazepine medications during pregnancy and potential risk for birth defects, National Birth Defects Prevention Study, 1997–2011

Tinker

Reefhuis

Bitsko

et al. 2019

Birth Defects Research

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Background: Benzodiazepine medications can be used to treat anxiety, a condition affecting 15% of women of childbearing age in the United States. Studies have shown conflicting results for the association between benzodiazepine use during pregnancy and birth defects. Methods: We analyzed 1997-2011 data from the National Birth Defects Prevention Study, a multisite, population-based case-control study. We assessed the prevalence of and factors associated with benzodiazepine use in pregnancy among mothers of live-born infants without a birth defect (control mothers). We used logistic regression to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the association between specific birth defects and benzodiazepine use; we estimated crude odds ratios (cORs) for defect categories with 3-4 exposed cases.Results: Exposure to benzodiazepines during pregnancy was rare (N = 93/11,614; 0.8%). Benzodiazepine use was more common among control mothers who were ≥30 years, non-Hispanic white, had more education, smoked, and took antidepressant medication. We observed significantly elevated ORs for any benzodiazepine and Dandy-Walker malformation (cOR: 3.1; 95% CI: 1.1, 8.6); for alprazolam and anophthalmia or microphthalmia (cOR: 4.0; 95% CI: 1.2, 13.1) and esophageal atresia or stenosis (aOR: 2.7; 95% CI: 1.2, 5.9); and lorazepam and pulmonary valve stenosis (cOR: 4.1; 95% CI: 1.2, 14.2), but sample sizes were limited and therefore CIs were wide. Conclusions: Our findings suggest that benzodiazepines use is rare and may be associated with risk for certain birth defects. However, these results need replication and should be interpreted with caution.

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Section: Discussionmentioning

confidence: 99%

Use of benzodiazepine medications during pregnancy and potential risk for birth defects, National Birth Defects Prevention Study, 1997–2011

Tinker

Reefhuis

Bitsko

et al. 2019

Birth Defects Research

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“…21 Identifying and classifying MCMs is not a simple process. 22,23 There are a wide variety of physical features such as birth marks, positional deformities, and minor anomalies that may be noted on routine neonatal examination, but would not qualify as MCMs when evaluated by an expert clinical dysmorphologist. This point was demonstrated in a study 24 that evaluated physical anomalies among a consecutive series of 1000 births and elective terminations to determine inclusion and exclusion criteria for malformations in newborn infants exposed to potential teratogens.…”

Section: Discussionmentioning

confidence: 99%

A systematic review of pregnancy exposure registries: examination of protocol-specified pregnancy outcomes, target sample size, and comparator selection

Gelperin

Hammad

Leishear

et al. 2016

Pharmacoepidemiol Drug Saf

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No registries were designed to have sufficient power to assess specific malformations, despite the plausibility that most teratogens cause specific defects. Only half of the registries included a power analysis. Despite their common use, external comparators, including MACDP, have important limitations. In the absence of randomized controlled trial data in pregnant women, pregnancy registries remain an important tool as part of a comprehensive pregnancy surveillance program; however, pregnancy registries alone may not be sufficient to obtain adequate data regarding risks of specific malformations. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

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“…The nature of such studies, regardless of methodological design, inherently carries substantial elements of heterogeneity. These pertain among other things to selection and characteristics of the study population and comparator group (if any); quality and validity of the exposure and outcome measurements and the level of confounder control [17,18]. These factors compromise to some extent comparisons across studies and represent a challenge in providing a summary of the evidence for decision support.…”

Section: General Methodsological Considerations and Findings In Indivimentioning

confidence: 99%

The Safety of Second-Generation Antipsychotics During Pregnancy: A Clinically Focused Review

Damkier

Videbech

2018

CNS Drugs

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The issue of antipsychotic treatment during pregnancy is subject to substantial uncertainty and some controversy among healthcare providers, specifically pertaining to second-generation antipsychotics (SGAs) that are subject to a large gap in safety data during pregnancy compared with antidepressants. The amount of safety data for the use of SGAs during pregnancy is rapidly increasing, thus constantly changing the level of evidence. We performed a clinically focused review on the safety of SGA during pregnancy. Twenty-three studies provided various pregnancy outcomes for 14,382 pregnant women exposed to an SGA during pregnancy. In utero exposure to aripiprazole, olanzapine, and quetiapine is not associated with increased risks of major congenital malformations, whereas risperidone and paliperidone may be associated with a very minor increased risk of congenital malformations. Safety data on ziprasidone and clozapine remain scarce and insufficient for a quantitative safety evaluation. No or minimal safety data are available for amisulpride, asenapine, lurasidone, and sertindole. For other pregnancy outcomes of interest, e.g. miscarriage, stillbirth, and small for gestational age, the available data overall do not suggest a clinically important increased risk, and do not allow for a meaningful stratification on individual drug level. Furthermore, for neonatal adaption and childhood neurodevelopment, the data do not allow for a meaningful risk assessment. It is imperative that factors in addition to safety data, e.g. individual disease history, characteristics and treatment response, adverse reaction profile, and patient preferences, be considered for the individual patient when choosing specific SGA treatment during pregnancy.

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Challenges in Studying Modifiable Risk Factors for Birth Defects

Cited by 41 publications

References 86 publications

Use of benzodiazepine medications during pregnancy and potential risk for birth defects, National Birth Defects Prevention Study, 1997–2011

Use of benzodiazepine medications during pregnancy and potential risk for birth defects, National Birth Defects Prevention Study, 1997–2011

A systematic review of pregnancy exposure registries: examination of protocol-specified pregnancy outcomes, target sample size, and comparator selection

The Safety of Second-Generation Antipsychotics During Pregnancy: A Clinically Focused Review

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