Maternal intake of vitamin E and birth defects,national birth defects prevention study, 1997 to 2005

BACKGROUND In a recent study, high maternal periconceptional intake of vitamin E was found to be associated with risk of congenital heart defects (CHDs). To explore this association further, we investigated the association between total daily vitamin E intake and selected birth defects. METHODS: We analyzed data from 4525 controls and 8665 cases from the 1997 to 2005 National Birth Defects Prevention Study. We categorized estimated periconceptional energy‐adjusted total daily vitamin E intake from diet and supplements into quartiles (referent, lowest quartile). Associations between quartiles of energy‐adjusted vitamin E intake and selected birth defects were adjusted for demographic, lifestyle, and nutritional factors. RESULTS: We observed a statistically significant association with the third quartile of vitamin E intake (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.01–1.35) and all CHDs combined. Among CHD sub‐types, we observed associations with left ventricular outflow tract obstruction defects, and its sub‐type, coarctation of the aorta and the third quartile of vitamin E intake. Among defects other than CHDs, we observed associations between anorectal atresia and the third quartile of vitamin E intake (OR, 1.66; 95% CI, 1.01–2.72) and hypospadias and the fourth quartile of vitamin E intake (OR, 1.42; 95% CI, 1.09–1.87). CONCLUSION: Selected quartiles of energy‐adjusted estimated total daily vitamin E intake were associated with selected birth defects. However, because these few associations did not exhibit exposure‐response patterns consistent with increasing risk associated with increasing intake of vitamin E, further studies are warranted to corroborate our findings. Birth Defects Research (Part A), 100:647–657, 2014. © 2014 Wiley Periodicals, Inc.     

Maternal age and non‐chromosomal birth defects,Atlanta—1968–2000: Teenager or thirty‐something,who is at risk?

OBJECTIVE: This investigation explored the association between maternal age and non-chromosomal birth defects to assess any increased risk associated with maternal age. METHODS: Birth defect cases were ascertained by the Metropolitan Atlanta Congenital Defects Program (MACDP), denominator information was obtained using birth certificate data. Infants with any chromosomal diagnosis were excluded. Effect estimates were calculated using 5-year maternal age categories with 25-29 years as the referent. Multiple logistic regression was used to adjust for maternal race, parity, infant sex, and birth year. RESULTS: A total of 1,050,616 singleton infants, born after > or = 20 weeks gestation in the five counties of metropolitan Atlanta from 1968 through 2000 who did not have a chromosomal abnormality and whose mother was 14 to 40 years old, were included in the analyses, 32,816 of them were identified with birth defects by the MACDP. Young maternal age (14-19 years) was associated with anencephaly (OR = 1.81, 95% CI = 1.30-2.52), hydrocephaly without neural tube defect (OR = 1.56, 95% CI = 1.23-1.96), all ear defects (OR = 1.28, 95% CI = 1.10-1.49), cleft lip (OR = 1.88, 95% CI = 1.30-2.73), female genital defects (OR = 1.57, 95% CI = 1.12-2.19), hydronephrosis (OR = 1.42, 95% CI = 1.11-1.82), polydactyly (OR = 1.29, 95% CI = 1.09-1.52), omphalocele (OR = 2.08, 95% CI = 1.39-3.12), and gastroschisis (OR = 7.18, 95% CI = 4.39-11.75). Advanced maternal age (35-40 years) was associated with all heart defects (OR = 1.12, 95% CI = 1.03-1.22), tricuspid atresia (OR = 1.24, 95% CI = 1.02-1.50), right outflow tract defects (OR = 1.28, 95% CI = 1.10-1.49), hypospadias 2nd degree or higher (OR = 1.85, 95% CI = 1.33-2.58), male genital defects excluding hypospadias (OR = 1.25, 95% CI = 1.08-1.45) and craniosynostosis (OR = 1.65, 95% CI = 1.18-2.30). CONCLUSIONS: Young and advanced maternal ages are associated with different types of birth defects. Underlying causes for these associations are not clear.     

Periconceptional maternal alcohol consumption and neural tube defects

BACKGROUND: Neural tube defects (NTD)s, which occur when the neural tube fails to close during early gestation, are some of the most common birth defects worldwide. Alcohol is a known teratogen and has been shown to induce NTDs in animal studies, although most human studies have failed to corroborate these results. Using data from the National Birth Defects Prevention Study, associations between maternal reports of periconceptional (1 month prior through 2 months postconception) alcohol consumption and NTDs were examined. METHODS: NTD cases and unaffected live born control infants, delivered from 1997 through 2005, were included. Interview reports of alcohol consumption (quantity, frequency, variability, and type) were obtained from 1223 case mothers and 6807 control mothers. Adjusted odds ratios (aOR)s and 95% confidence intervals were estimated using multivariable logistic regression analysis. RESULTS: For all NTDs combined, most aORs for any alcohol consumption, one or more binge episodes, and different type(s) of alcohol consumed were near unity or modestly reduced (≥0.7<aOR≤1.1) and were not statistically significant. Findings were similar for individual NTD subtypes. CONCLUSIONS: These findings suggest no elevated association between maternal periconceptional alcohol consumption and NTDs. Underreporting of alcohol consumption, due to negative social stigma associated with alcohol consumption during pregnancy, and limited reports for mothers with early pregnancy loss of a fetus with an NTD may have affected the estimated odds ratios. Future studies should aim to increase sample sizes for less prevalent subtypes, reduce exposure misclassification, and improve ascertainment offetal deaths and elective terminations. Birth Defects Research (Part A), 2013. © 2013 Wiley Periodicals, Inc.     

The Effects of Periconceptional Risk Factor Exposure and Micronutrient Supplementation on Birth Defects in Shaanxi Province in Western China

Objectives

1) To understand the current prevalence and main types of birth defects, 2) assess the periconceptional exposure of factors associated with birth defects in Shaanxi Province, and 3) provide scientific evidence for local governments to formulate services for the primary prevention of birth defects.

Methods

We sampled 16,541 households from 128 townships in 16 counties/districts in Shaanxi province using a multi-stage random sampling method. Among them, 10,544 women who had live born or stillborn infants with gestational age ≥28 weeks between 2008 and 2009 were interviewed using a structured questionnaire designed to collect information about periconceptional risk factor exposure, health care service utilization, and micronutrient supplements. Logistic regression was performed to assess the risk factors associated with birth defects and adjustments were made for imbalanced social-demographic characteristics between case and control groups.

Results

The prevalence of congenital birth defect in Shaanxi province was 14.3/1000 births. The environment risk factors associated with birth defects include unhealthy lifestyle (Alcohol, odds ratio (OR): 3.60, 95% confidence interval (CI) 1.64−7.91; Smoking, OR: 1.32, 95% CI: 0.99−1.75; Drink strong tea, OR: 1.81, 95% CI: 1.27−2.59), exposure to heavy pollution (OR: 1.53, 95% CI: 1.01−2.30), maternal diseases (OR: 1.77, 95% CI: 1.35−2.33), drug use (OR: 2.11, 95% CI: 1.51−2.95), maternal chemical pesticide exposure (OR: 2.30, 95% CI: 1.16−4.57), and adverse pregnancy history (OR: 10.10, 95% CI: 7.55−13.53). Periconceptional folic acid or multiple micronutrients including folic acid supplementation, was associated with a reduced rate of birth defects (OR: 0.54, 95% CI: 0.29−0.998).

Conclusions

Health care service utilization, unhealthy lifestyle factors, and environment risk factors seem to be associated with birth defects in Shaanxi province. Governmental agencies should focus on effective primary preventative methods, such as the delivery of periconceptional health education for minimizing potential risk factor exposures, periconceptional folic acid or micronutrient supplementation, environment monitoring, and assessment of factories with high levels of pollution.     

Maternal obesity and morbid obesity: The risk for birth defects in the offspring

BACKGROUND : The objective of this study was to assess, in a large data set from Swedish Medical Health Registries, whether maternal obesity and maternal morbid obesity were associated with an increased risk for various structural birth defects. METHODS : The study population consisted of 1,049,582 infants born in Sweden from January 1, 1995, through December 31, 2007, with known maternal weight and height data. Women were grouped in six categories of body mass index (BMI) according to World Health Organization classification. Infants with congenital birth defects were identified from three sources: the Swedish Medical Birth Registry, the Register of Birth Defects, and the National Patient Register. Maternal age, parity, smoking, and year of birth were thought to be potential confounders and were included as covariates in the adjusted odds ratio analyses. RESULTS : Ten percent of the study population was obese. Morbid obesity (BMI ≥ 40) occurred in 0.7%. The prevalence of congenital malformations was 4.7%, and the prevalence of relatively severe malformations was 3.2%. Maternal prepregnancy morbid obesity was associated with neural tube defects OR 4.08 (95% CI 1.87–7.75), cardiac defects OR 1.49 (95% CI 1.24–1.80), and orofacial clefts OR 1.90 (95% CI 1.27–2.86). Maternal obesity (BMI ≥ 30) significantly increased the risk of hydrocephaly, anal atresia, hypospadias, cystic kidney, pes equinovarus, omphalocele, and diaphragmatic hernia. CONCLUSION : The risk for a morbidly obese pregnant woman to have an infant with a congenital birth defect is small, but for society the association is important in the light of the ongoing obesity epidemic. Birth Defects Research (Part A), 2010. © 2009 Wiley‐Liss, Inc.     

Association between reported venlafaxine use in early pregnancy and birth defects,national birth defects prevention study, 1997–2007

BACKGROUND

Few epidemiologic studies have investigated the use of venlafaxine (Effexor XR capsules, Product Monograph, Wyeth, Montreal, Canada), an antidepressant used to treat major depression and anxiety disorders in adults, during pregnancy. Our objective was to determine whether use of venlafaxine during pregnancy is associated with specific birth defects.

METHODS

We used data from the National Birth Defects Prevention Study (NBDPS), a population‐based, case‐control study in the United States. Our analysis included mothers with pregnancies affected by one of 30 selected birth defects (cases) and babies without birth defects (controls) with estimated dates of delivery between 1997 and 2007. Exposure was any reported use of venlafaxine from 1 month preconception through the third month of pregnancy. We calculated adjusted odds ratios (aORs) and 95% Fisher Exact confidence intervals (CIs) for 24 birth defect groups for which at least 400 case mothers were interviewed. Our adjusted analyses controlled for maternal age and race/ethnicity.

RESULTS

Among the 27,045 NBDPS participants who met inclusion criteria, 0.17% (14/8002) of control mothers and 0.40% (77/19,043) of case mothers reported any use of venlafaxine from 1 month preconception through the third month of pregnancy. Statistically significant associations were found for anencephaly, atrial septal defect (ASD) secundum, or ASD not otherwise specified, coarctation of the aorta, cleft palate, and gastroschisis.

CONCLUSIONS

Our data suggest associations between periconceptional use of venlafaxine and some birth defects. However, sample sizes were small, CIs were wide, and additional studies are needed to confirm these results. Birth Defects Research (Part A), 2013. © 2012 Wiley Periodicals, Inc.     

Lack of maternal folic acid supplementation is associated with heart defects in Down syndrome: a report from the National Down Syndrome Project

BACKGROUND: Maternal folic acid supplementation has been associated with a reduced risk for neural tube defects and may be associated with a reduced risk for congenital heart defects and other birth defects. Individuals with Down syndrome are at high risk for congenital heart defects and have been shown to have abnormal folate metabolism. METHODS: As part of the population‐based case‐control National Down Syndrome Project, 1011 mothers of infants with Down syndrome reported their use of supplements containing folic acid. These data were used to determine whether a lack of periconceptional maternal folic acid supplementation is associated with congenital heart defects in Down syndrome. We used logistic regression to test the relationship between maternal folic acid supplementation and the frequency of specific heart defects correcting for maternal race or ethnicity, proband sex, maternal use of alcohol and cigarettes, and maternal age at conception. RESULTS: Lack of maternal folic acid supplementation was more frequent among infants with Down syndrome and atrioventricular septal defects (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.08–2.63; p = 0.011) or atrial septal defects (OR, 1.69; 95% CI, 1.11–2.58; p = 0.007) than among infants with Down syndrome and no heart defect. Preliminary evidence suggests that the patterns of association differ by race or ethnicity and sex of the proband. There was no statistically significant association with ventricular septal defects (OR, 1.26; 95% CI, 0.85–1.87; p = 0.124). CONCLUSIONS: Our results suggest that lack of maternal folic acid supplementation is associated with septal defects in infants with Down syndrome. Birth Defects Research (Part A), 2011. © 2011 Wiley‐Liss, Inc.     

Craniosynostosis and maternal smoking

BACKGROUND: Several previous studies suggested increased risk of craniosynostosis among infants born to women who smoked. METHODS: This study used data from the National Birth Defects Prevention Study, a multi‐state, population‐based case‐control study of infants delivered from 1997–2003. Nonmalformed, liveborn controls were selected randomly from birth certificates or birth hospitals. Data from maternal telephone interviews were available for 531 cases and 5008 controls. RESULTS: Smoking during the first month of pregnancy was not associated with craniosynostosis. Smoking later in pregnancy was associated with increased risk, but only among mothers who smoked at least one pack/day. For example, during the second trimester, the odds ratio for smoking <5 cigarettes/day was 1.0 (95% confidence interval [CI] 0.6, 1.8), but the odds ratio (OR) for smoking 15 or more cigarettes/day was 1.6 (95% CI 0.9, 2.8), after adjustment for maternal age, education, race‐ethnicity, sub‐fertility, parity, folic acid supplement intake, body mass index, and study center. Among women who did not smoke, adjusted odds ratios suggested that secondhand smoke exposure at home, but not at work/school, was associated with modestly increased risk; the OR for home exposure was 1.3 (95% CI 0.9, 1.9). Results followed a similar pattern for some, but not all, specific suture types, but numbers for some groupings were small. CONCLUSIONS: The results suggest moderately increased risk of craniosynostosis among mothers who were the heaviest smokers and who continued to smoke after the first trimester. Results are somewhat equivocal, given that most confidence intervals included one. Birth Defects Research (Part A), 2008. © 2007 Wiley‐Liss, Inc.     

Maternal self-reported genital tract infections during pregnancy and the risk of selected birth defects

BACKGROUND: Genital tract infections are common during pregnancy and can result in adverse outcomes including preterm birth and neonatal infection. This hypothesis‐generating study examined whether these infections are associated with selected birth defects. METHODS: We conducted a case‐control study of 5913 children identified as controls and 12,158 cases with birth defects from the National Birth Defects Prevention Study (1997–2004). Maternal interviews provided data on genital tract infections that occurred from one month before pregnancy through the end of the first trimester. Infections were either grouped together as a single overall exposure or were considered as a subgroup that included chlamydia/gonorrhea/pelvic inflammatory disease. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression with adjustment for potential confounders. RESULTS: Genital tract infections were associated with bilateral renal agenesis/hypoplasia (OR, 2.89; 95% CI, 1.11–7.50), cleft lip with or without cleft palate (OR, 1.46; 95% CI, 1.03–2.06), and transverse limb deficiency (OR, 1.84; 95% CI, 1.04–3.26). Chlamydia/gonorrhea/pelvic inflammatory disease was associated with cleft lip only (OR, 2.81; 95% CI, 1.39–5.69). These findings were not statistically significant after adjustment for multiple comparisons. CONCLUSIONS: Caution is needed in interpreting these findings due to the possible misclassification of infection, the limited sample size that constrained consideration of the effects of treatment, and the possibility of chance associations. Although these data do not provide strong evidence for an association between genital tract infections and birth defects, additional research on the possible effects of these relatively common infections is needed. Birth Defects Research (Part A), 2010. © 2010 Wiley‐Liss, Inc.     

Maternal periconceptional smoking and alcohol consumption and risk for select congenital anomalies

BACKGROUND: This study examined the association between maternal smoking and alcohol use (including binge drinking) during the periconceptional period (i.e., 2 months before through 2 months after conception) and the risk of orofacial clefts, NTDs, and conotruncal heart defects in offspring. METHODS: Data were drawn from a population‐based case‐control study of fetuses and live‐born infants among a cohort of California births between July 1999 and June 2003. The 1,355 cases comprised of 701 orofacial clefts, 337 NTDs, and 323 conotruncal heart defects. Information on smoking and alcohol consumption was obtained via telephone interviews with mothers of 1,355 (80% of eligibles) cases and 700 (77% of eligibles) nonmalformed, live‐born controls. RESULTS: Maternal smoking of five cigarettes or less per day was associated with reduced risks of NTDs (OR 0.7; 95% CI: 0.3, 1.4), whereas the risk associated with higher cigarette consumption was lower for conotruncal heart defects (OR 0.5; 95% CI: 0.2, 1.2). Maternal intake of alcohol less than 1 day per week was associated with a 1.6‐ to 2.1‐fold higher risk of NTDs (95% CI: 0.9, 2.6), d‐transposition of the great arteries (95% CI: 1.1, 3.2), and multiple cleft lip with or without cleft palate (CLP) (95% CI: 0.8, 4.5). Risks associated with more frequent alcohol intake were 2.1 for NTDs (95% CI: 1.1, 4.0) and 2.6 for multiple CLP (95% CI: 1.1, 6.1). CONCLUSIONS: This study observed that maternal alcohol intake increased the risk for d‐transposition of the great arteries, NTDs, and multiple CLP in infants. By contrast, smoking was associated with a lower risk of NTDs and conotruncal heart defects. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.     

Maternal thyroid disease,thyroid medication use,and selected birth defects in the National Birth Defects Prevention Study

BACKGROUND: Although thyroid disorders are present in approximately 3% of pregnant women, little is known about the association between maternal thyroid disease and birth defects. METHODS: We assessed the association between maternal thyroid disease, thyroid medication use, and 38 types of birth defects among 14,067 cases and 5875 controls in the National Birth Defects Prevention Study, a multisite, population‐based, case‐control study. Infants in this study were born between October 1997 and December 2004. Information on exposures including maternal diseases and use of medications was collected by telephone interview. RESULTS: We found statistically significant associations between maternal thyroid disease and left ventricular outflow tract obstruction heart defects (1.5; 95% CI, 1.0–2.3), hydrocephaly (2.9; 95% CI, 1.6–5.2), hypospadias (1.6; 95% CI, 1.0–2.5), and isolated anorectal atresia (2.4; 95% CI, 1.2–4.6). Estimates for the association between periconceptional use of thyroxine and specific types of birth defects were similar to estimates for any thyroid disease. Given that antithyroid medication use was rare, we could not adequately assess risks for their use for most case groups. CONCLUSIONS: Our results are consistent with the positive associations between maternal thyroid disease or thyroid medication use and both hydrocephaly and hypospadias observed in some previous studies. New associations with left ventricular outflow tract obstruction heart defects and anorectal atresia may be chance findings. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.     

Medications used to treat nausea and vomiting of pregnancy and the risk of selected birth defects

BACKGROUND Nausea and vomiting of pregnancy (NVP) occurs in up to 80% of pregnant women, but its association with birth outcomes is not clear. Several medications are used for the treatment of NVP; however, data are limited on their possible associations with birth defects. METHODS Using data from the National Birth Defects Prevention Study (NBDPS)—a multi‐site, population‐based, case‐control study—we examined whether NVP or its treatment was associated with the most common noncardiac defects in the NBDPS (nonsyndromic cleft lip with or without cleft palate [CL/P], cleft palate alone [CP], neural tube defects, and hypospadias) compared with randomly selected nonmalformed live births. RESULTS Among the 4524 cases and 5859 controls included in this study, 67.1% reported first‐trimester NVP, and 15.4% of them reported using at least one agent for NVP. Nausea and vomiting of pregnancy was not associated with CP or neural tube defects, but modest risk reductions were observed for CL/P (adjusted odds ratio [aOR] = 0.87; 95% confidence interval [CI], 0.77–0.98) and hypospadias (aOR = 0.84; 95% CI, 0.72–0.98). Regarding treatments for NVP in the first trimester, the following adjusted associations were observed with an increased risk: proton pump inhibitors and hypospadias (aOR = 4.36; 95% CI, 1.21–15.81), steroids and hypospadias (aOR = 2.87; 95% CI, 1.03–7.97), and ondansetron and CP (aOR = 2.37; 95% CI, 1.18–4.76), whereas antacids were associated with a reduced risk for CL/P (aOR = 0.58; 95% CI, 0.38–0.89). CONCLUSIONS NVP was not observed to be associated with an increased risk of birth defects; however, possible risks related to three treatments (i.e., proton pump inhibitors, steroids and ondansetron), which could be chance findings, warrant further investigation. Birth Defects Research (Part A) 2012. © 2011 Wiley Periodicals, Inc.     

Vasoactive exposures during pregnancy and risk of microtia

BACKGROUND

Little is known about the etiology of nonsyndromic microtia. This study investigated the hypothesis that microtia is caused by vascular disruption.

METHODS

The study analyzed data from the population‐based National Birth Defects Prevention Study (NBDPS) for deliveries between 1997 and 2005. Four hundred eleven nonsyndromic cases of microtia, with or without additional defects, were compared to 6560 nonmalformed infants with respect to maternal exposures to vasoactive medications and smoking during the periconceptional period and conditions that have previously been associated with vascular events (multiple gestation, maternal history of type 1, type 2, or gestational diabetes, and hypertension). Odds ratios (ORs) were estimated with multivariable models, controlling for the effects of race/ethnicity, education, periconceptional folic acid use, and study center.

RESULTS

Risk estimates for vasoactive medications and smoking were not meaningfully increased. Maternal type 1/2 diabetes was diagnosed before or during the index pregnancy in 4% and 1% of cases, respectively, compared to 1% and 0.05% of controls; the adjusted OR for these two groups combined was 7.2 (95% confidence interval [CI], 3.9–13.1). Gestational diabetes was observed for 9% of cases and 6% of controls; the OR was moderately elevated (OR, 1.4; 95% CI, 0.9–2.0). ORs were also increased for multiple gestations (OR, 2.5; 95% CI, 1.5–4.2) and pre‐existing hypertension (OR, 1.6; 95% CI, 1.0–2.5).

CONCLUSIONS

Because ORs were only elevated for diabetes and not for vasoactive exposures or other potential vascular events, findings suggest that some microtia occurrences may be part of the diabetic embryopathy rather than manifestations of vascular disruption. Birth Defects Research (Part A), 2013. © 2012 Wiley Periodicals, Inc.     

Periconceptional parental conditions and perimembranous ventricular septal defects in the offspring

Background: The perimembranous ventricular septal (pVSD) defect is the most common congenital heart disease phenotype. Several parental factors are associated with pVSD risk in the offspring. To contribute to the future prevention of pVSDs, we investigated associations with nongenetic parental conditions. Methods: In a case–control study with standardized data collection at 17 months after birth, 115 parents of a child with pVSD and 484 parents of a healthy child completed questionnaires about periconceptional nongenetic conditions. Univariable and multivariable logistic regression analyses were used to estimate odds ratios (OR) with 95% confidence intervals (95% CI). Results: Complete data were available for 588 families (98%). Maternal risk conditions associated with pVSD offspring were a positive family history of congenital heart disease (OR, 2.61; 95%CI, 0.98–6.91), medication use (OR, 1.80; 95%CI, 1.13–2.85) and advanced age (OR, 1.07; 95%CI, 1.02–1.12). Exposure to phthalates (OR, 1.93; 95%CI, 1.05–3.54) was the only paternal risk condition associated with pVSD offspring. Conclusion: Four periconceptional parental conditions contributed to pVSD risk in the offspring. Couples planning pregnancy should be counseled on these risk conditions which are partially modifiable to contribute to the future prevention of pVSDs. Birth Defects Research (Part A) 100:944–950, 2014. © 2014 Wiley Periodicals, Inc.     

Feasibility of using the national hospital discharge survey to estimate the prevalence of selected birth defects

BACKGROUND: Nationally representative data on the prevalence of certain birth defects are largely unavailable. We evaluated the feasibility of using data from the National Hospital Discharge Survey (NHDS) to describe the prevalence of selected birth defects. METHODS: All live births recorded in the NHDS during 1999-2001 were included. The prevalence for selected birth defects was calculated using weighted ratio estimators. Prevalence ratios comparing the NHDS estimates to published national estimates from the National Birth Defects Prevention Network (NBDPN) were calculated. RESULTS: With the exception of common truncus, the NHDS prevalence for the selected defects was consistently lower than the NBDPN estimates. The prevalence ratios ranged from 0.38 for trisomy 18 and anopthalmia/micropthalmia to 1.16 for common truncus. The NHDS prevalence estimates for spina bifida without anencephaly (PR 0.89, 95% CI: 0.57-1.22) and gastroschisis/omphalocele (PR 0.94, 95% CF: 0.48-1.40) most closely approximated the NBDPN estimates. CONCLUSIONS: NHDS data underestimate the prevalence of most birth defects. Additional research is needed to determine whether NHDS estimates may be useful for evaluating trends in certain conditions. Surveillance systems employing active case-finding continue to provide more accurate estimates of birth defects prevalence.     

Early pregnancy azathioprine use and pregnancy outcomes

BACKGROUND: Azathioprine (AZA) is used during pregnancy by women with inflammatory bowel disease (IBD), other autoimmune disorders, malignancy, and organ transplantation. Previous studies have demonstrated potential risks. METHODS: The Swedish Medical Birth Register was used to identify 476 women who reported the use of AZA in early pregnancy. The effect of AZA exposure on pregnancy outcomes was studied after adjustment for maternal characteristics that could act as confounders. RESULTS: The most common indication for AZA use was IBD. The rate of congenital malformations was 6.2% in the AZA group and 4.7% among all infants born (adjusted OR: 1.41, 95% CI: 0.98–2.04). An association between early pregnancy AZA exposure and ventricular/atrial septal defects was found (adjusted OR: 3.18, 95% CI: 1.45–6.04). Exposed infants were also more likely to be preterm, to weigh <2500 gm, and to be small for gestational age compared to all infants born. This effect remained for preterm birth and low birth weight when infants of women with IBD but without AZA exposure were used as a comparison group. A trend toward an increased risk of congenital malformations was found among infants of women with IBD using AZA compared to women with IBD not using AZA (adjusted OR: 1.42, 95% CI: 0.93–2.18). CONCLUSIONS: Infants exposed to AZA in early pregnancy may be at a moderately increased risk of congenital malformations, specifically ventricular/atrial septal defects. There is also an increased risk of growth restriction and preterm delivery. These associations may be confounded by the severity of maternal illness. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.     

Omphalocele and gastroschisis: Black-White disparity in infant survival

BACKGROUND: Racial/ethnic variations in the occurrence of abdominal wall defects have been previously noted but it remains poorly understood whether race/ethnicity is a determinant of survival among affected infants. METHODS: Study was conducted on cases of gastroschisis and omphalocele recorded for the years 1983-1999 at the New York Congenital Malformation Registry. Adjusted and unadjusted hazard ratios were generated from a Proportional Hazards Regression model to compare survival among affected Blacks, Hispanics and Whites. The major end point of analysis was differences in all cause mortality among infants with abdominal wall birth defects across different racial/ethnic groups. RESULTS: Among the three racial/ethnic groups, 1481 infants were diagnosed with either omphalocele (978 or 66%) or gastroschisis (503 or 34%). Overall infant mortality rate (IMR) was 182 per 1000, with 74% of the deaths occurring within the first 28 days of life. Omphalocele infants had significantly higher infant mortality (IMR = 215 per 1000) than infants with gastroschisis (IMR = 118 per 1000)[p < 0.0001]. Overall, Black infants with abdominal wall defects had lower mortality indices than Whites and Hispanics. However, when considered as separate disease entities, Black infants were twice as likely to survive as compared to Whites if they had omphalocele [Adjusted Hazard Ratio (AHR) = 0.52; 95% Confidence Interval (CI) = 0.37-0.74], and twice as likely to die as Whites if they had gastroschisis instead (AHR = 2.23; 95% CI = 1.16-4.28). For both defect subtypes, Hispanics have risks for infant mortality comparable to Whites. CONCLUSIONS: The natural history of omphalocele and gastroschisis co-varies with race. Black infants with gastroschisis have worse survival outcomes while those with omphalocele have better chances of survival than their White or Hispanic counterparts.     

Evaluation of preterm births and birth defects in liveborn infants of US military women who received smallpox vaccine

BACKGROUND: Women serving in the US military have some unique occupational exposures, including exposure to vaccinations that are rarely required in civilian professions. When vaccinations are inadvertently given during pregnancy, such exposures raise special concerns. These analyses address health outcomes, particularly preterm births and birth defects, among infants who appear to have been exposed to maternal smallpox vaccination in pregnancy. METHODS: This retrospective cohort study included 31,420 infants born to active‐duty military women during 2003–2004. We used Department of Defense databases to define maternal vaccination and infant health outcomes. Multivariable regression models were developed to describe associations between maternal smallpox vaccination and preterm births and birth defects in liveborn infants. RESULTS: There were 7,735 infants identified as born to women ever vaccinated against smallpox, and 672 infants born to women vaccinated in the first trimester of pregnancy. In multivariable modeling, maternal smallpox vaccination in pregnancy was not associated with preterm or extreme preterm delivery. Maternal smallpox vaccination in the first trimester of pregnancy was not significantly associated with overall birth defects (OR 1.40; 95% CI: 0.94, 2.07), or any of seven specific defects individually modeled. CONCLUSIONS: Results may be reassuring that smallpox vaccine, when inadvertently administered to pregnant women, is not associated with preterm delivery or birth defects in liveborn infants. Birth Defects Research (Part A) 2008. © 2008 Wiley‐Liss, Inc.     

Are birth defects among Hispanics related to maternal nativity or number of years lived in the United States?

BACKGROUND: Literature on the risk of birth defects among foreign‐ versus U.S.–born Hispanics is limited or inconsistent. We examined the association between country of birth, immigration patterns, and birth defects among Hispanic mothers. METHODS: We used data from the National Birth Defects Prevention Study and calculated odds ratios (ORs) and 95% confidence intervals and assessed the relationship between mothers' country of birth, years lived in the United States, and birth defects among 575 foreign‐born compared to 539 U.S.–born Hispanic mothers. RESULTS: Hispanic mothers born in Mexico/Central America were more likely to deliver babies with spina bifida (OR = 1.53) than their U.S.–born counterparts. Also, mothers born in Mexico/Central America or who were recent United States immigrants (≤5 years) were less likely to deliver babies with all atrial septal defects combined, all septal defects combined, or atrial septal defect, secundum type. However, Hispanic foreign‐born mothers who lived in the United States for >5 years were more likely to deliver babies with all neural tube defects combined (OR = 1.42), spina bifida (OR = 1.89), and longitudinal limb defects (OR = 2.34). Foreign‐born mothers, regardless of their number of years lived in the United States, were more likely to deliver babies with anotia or microtia. CONCLUSIONS: Depending on the type of birth defect, foreign‐born Hispanic mothers might be at higher or lower risk of delivering babies with the defects. The differences might reflect variations in predisposition, cultural norms, behavioral characteristics, and/or ascertainment of the birth defects. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.