Cheryl S. Broussard

Maternal treatment with opioid analgesics and risk for birth defects

OBJECTIVE We examined whether maternal opioid treatment between 1 month before pregnancy and the first trimester was associated with birth defects. STUDY DESIGN The National Birth Defects Prevention Study (1997 through 2005) is an ongoing population-based case-control study. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIS) for birth defects categories with at least 200 case infants or at least 4 exposed case infants. RESULTS Therapeutic opioid use was reported by 2.6% of 17,449 case mothers and 2.0% of 6701 control mothers. Treatment was statistically significantly associated with conoventricular septal defects (OR, 2.7; 95% CI, 1.1-6.3), atrioventricular septal defects (OR, 2.0; 95% CI, 1.2-3.6), hypoplastic left heart syndrome (OR, 2.4; 95% CI, 1.4-4.1), spina bifida (OR, 2.0; 95% CI, 1.3-3.2), or gastroschisis (OR, 1.8; 95% CI, 1.1-2.9) in infants. CONCLUSION Consistent with some previous investigations, our study shows an association between early pregnancy maternal opioid analgesic treatment and certain birth defects. This information should be considered by women and their physicians who are making treatment decisions during pregnancy.

Orofacial clefts in the National Birth Defects Prevention Study, 1997-2004.

Orofacial clefts are among the most common types of birth defects, but their clinical presentation has not been well described in a geographically diverse US population. To describe the birth prevalence and phenotype of nonsyndromic clefts, we used data from the National Birth Defects Prevention Study (NBDPS), a multi‐site, population‐based, case‐control study aimed at identifying genetic and environmental risk factors for birth defects. Included in the study were infants born during 1997–2004 with a cleft lip (CL), cleft lip with cleft palate (CLP), or cleft palate (CP). Infants with clefts associated with recognized single‐gene disorders, chromosome abnormalities, holoprosencephaly, or amniotic band sequence were excluded. A total of 3,344 infants with nonsyndromic orofacial clefts were identified, including 751 with CL, 1,399 with CLP, and 1,194 with CP, giving birth prevalence estimates of 0.3, 0.5, and 0.4/1,000 live births, respectively. Among infants with CLP where cleft laterality was specified, about twice as many had unilateral vs. bilateral involvement, while for CL there were over 10 times as many with unilateral versus bilateral involvement. Involvement was most often left‐sided. About one‐quarter of infants with CP had Pierre Robin sequence. Over 80% of infants had an isolated orofacial cleft. Among infants with CL or CLP, heart, limb, and other musculoskeletal defects were most commonly observed, while heart, limb, and central nervous system defects were most common among infants with CP. Better understanding of the birth prevalence and phenotype may help guide clinical care as well as contribute to an improved understanding of pathogenesis. Published 2009 Wiley‐Liss, Inc.

Herbal use before and during pregnancy

OBJECTIVE We estimated the prevalence and patterns of herbal use among US women before and during pregnancy. STUDY DESIGN The National Birth Defects Prevention Study is an ongoing, population-based, case-control study. This analysis included 4239 women from 10 centers in the United States who delivered infants without major birth defects from 1998-2004. RESULTS The prevalence of reported herbal use 3 months before or during pregnancy was 10.9%. During pregnancy, prevalence was 9.4% and was highest in the first trimester. Higher prevalence was associated with age greater than 30 years and education greater than 12 years. Use varied considerably by state (5-17%). Ginger and ephedra were the most commonly reported products early in pregnancy; teas and chamomile were most commonly reported throughout pregnancy. CONCLUSION Potentially 395,000 US births annually involve antenatal exposure to herbal products. Health care providers should inquire routinely about herbal use and educate patients about what little is known regarding risks of these products.

Association between maternal age and birth defects of unknown etiology: United States, 1997-2007.

BACKGROUND Birth defects affect 3% of babies born, and are one of the leading causes of infant mortality. Both younger and older maternal age may pose increased risks for certain birth defects. This study assessed the relationship between maternal age at the estimated delivery date and the risk for birth defects. METHODS Data were obtained from the National Birth Defects Prevention Study, a population-based case-control study including mothers across 10 states. Maternal age was stratified into six categories: <20, 20 to 24, 25 to 29, 30 to 34, 35 to 39, and ≥40 years, and also analyzed as a continuous variable. Logistic regression models adjusted formaternal race/ethnicity, education, body mass index (BMI), folic acid use, smoking, gravidity, and parental age difference were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS For maternal age <20 years, associations with total anomalous pulmonary venous return (aOR, 2.3; 95% CI, 1.3-4.0), amniotic band sequence (aOR, 2.4; 95% CI, 1.5-3.8), and gastroschisis (aOR, 6.1; 95% CI, 4.8-8.0) were observed. For the ≥40 year age group, associations with several cardiac defects, esophageal atresia (aOR, 2.9; 95% CI, 1.7-4.9), hypospadias (aOR, 2.0; 95% CI, 1.4-3.0), and craniosynostosis (aOR, 1.6; 95% CI, 1.1-2.4) were observed. Results using maternal age as a continuous variable were consistent with those that used categorized maternal age. CONCLUSION Elucidating risk factors specific to women ateither extreme of maternal age may offer prevention opportunities. All women should be made aware of prevention opportunities, such as folic acid supplementation, to reduce the occurrence of birth defects.

Exposure to Helicobacter pylori-positive Siblings and Persistence of Helicobacter pylori Infection in Early Childhood

Objectives: Cross-sectional studies suggest that Helicobacter pylori may be transmitted between siblings. The present study aimed to estimate the effect of an H pylori–infected sibling on the establishment of a persistent H pylori infection. Materials and Methods: The authors used data collected from a Texas–Mexico border population from 1998 to 2005 (the “Pasitos Cohort Study”). Starting at age 6 months, H pylori and factors thought to be associated with H pylori were ascertained every 6 months for participants and their younger siblings. Hazard ratios were estimated from proportional hazards regression models with household-dependent modeling. Results: Persistent H pylori infection in older siblings always preceded persistent infection in younger siblings. After controlling for mothers H pylori status, breast-feeding, antibiotic use, and socioeconomic factors, a strong effect was estimated for persistent H pylori infection in an older sibling on persistent infection in a younger sibling (hazard ratio 7.6, 95% confidence interval 1.6–37], especially when the difference in the age of the siblings was less than or equal to 3 years (hazard ratio 16, 95% confidence interval 2.5–112). Conclusions: These results suggest that when siblings are close in age, the older sibling may be an important source of H pylori transmission for younger siblings.

Antibiotics taken for other illnesses and spontaneous clearance of Helicobacter pylori infection in children

Factors that determine persistence of untreated Helicobacter pylori (H. pylori) infection in childhood are not well understood. We estimated risk differences for the effect of incidental antibiotic exposure on the probability of a detected clearance at the next test after an initial detected H. pylori infection.

Safe lists for medications in pregnancy: inadequate evidence base and inconsistent guidance from Web-based information, 2011

Medication use during pregnancy is common and increasing. Women are also increasingly getting healthcare information from sources other than their physicians.

Racial/Ethnic Differences in Infant Mortality Attributable to Birth Defects by Gestational Age

OBJECTIVE: Birth defects are a leading cause of infant mortality in the United States. Previous reports have highlighted black-white differences in overall infant mortality and infant mortality attributable to birth defects (IMBD). We evaluated the impact of gestational age on US racial/ethnic differences in IMBD. METHODS: We estimated the rate of IMBD as the underlying cause of death using the period-linked birth/infant death data for US residents for January 2003 to December 2006. We excluded infants with missing gestational age, implausible values based on Alexander’s index of birth weight for gestational age norms, or gestational ages <20 weeks or >44 weeks; we categorized gestational age into 3 groups: 20 to 33, 34 to 36, and 37 to 44 weeks. Using Poisson regression, we compared neonatal and postneonatal IMBD for infants of non-Hispanic black and Hispanic mothers with that for infants of non-Hispanic white mothers stratified by gestational age. RESULTS: IMBD occurred in 12.2 per 10 000 live births. Among infants delivered at 37 to 44 weeks, blacks (and Hispanics, to a lesser degree) had significantly higher neonatal and postneonatal IMBD than whites; however, among infants delivered at 20 to 33 or 34 to 36 weeks, neonatal (but not postneonatal) IMBD was significantly lower among blacks compared with whites. CONCLUSIONS: Racial/ethnic differences in IMBD were not explained in these data by differences in gestational age. Further investigation should include an assessment of possible racial/ethnic differences in severity and/or access to timely diagnosis and management of birth defects.

Maternal Medication and Herbal Use and Risk for Hypospadias: Data from the National Birth Defects Prevention Study, 1997--2007

To investigate associations between maternal use of common medications and herbals during early pregnancy and risk for hypospadias in male infants.

Influencing clinical practice regarding the use of antiepileptic medications during pregnancy: modeling the potential impact on the prevalences of spina bifida and cleft palate in the United States.

Selected antiepileptic drugs (AEDs) increase the risk of birth defects. To assess the impact of influencing AED prescribing practices on spina bifida and cleft palate we searched the literature for estimates of the association between valproic acid or carbamazepine use during pregnancy and these defects and summarized the associations using meta‐analyses. We estimated distributions of the prevalence of valproic acid and carbamazepine use among women of childbearing age based on analyses of four data sets. We estimated the attributable fractions and the number of children born with each defect that could be prevented annually in the United States if valproic acid and carbamazepine were not used during pregnancy. The summary odds ratio estimate for the association between valproic acid and spina bifida was 11.9 (95% uncertainty interval (UI): 4.0–21.2); for valproic acid and cleft palate 5.8 (95% UI: 3.3–9.5); for carbamazepine and spina bifida 3.6 (95% UI: 1.3–7.8); and for carbamazepine and cleft palate 2.4 (95% UI: 1.1–4.5) in the United States. Approximately 40 infants (95% UI: 10–100) with spina bifida and 35 infants (95% UI: 10–70) with cleft palate could be born without these defects each year if valproic acid were not used during pregnancy; 5 infants (95% UI: 0–15) with spina bifida and 5 infants (95% UI: 0–15) with cleft palate could be born without these defects each year if carbamazepine were not used during pregnancy. This modeling approach could be extended to other medications to estimate the impact of translating pharmacoepidemiologic data to evidence‐based prenatal care practice. Published 2011 Wiley‐Liss, Inc.