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.     

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.     

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.     

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.     

Associations between periconceptional alcohol consumption and craniosynostosis, omphalocele, and gastroschisis

BACKGROUND: Alcohol consumption during pregnancy is known to be associated with certain birth defects, but the risk of other birth defects is less certain. The authors examined associations between maternal alcohol consumption during pregnancy and craniosynostosis, omphalocele, and gastroschisis among participants in the National Birth Defects Prevention Study, a large, multicenter case–control study. METHODS: A total of 6622 control infants and 1768 infants with birth defects delivered from 1997–2005 were included in the present analysis. Maternal alcohol consumption was assessed as any periconceptional consumption (1 month prepregnancy through the third pregnancy month), and by quantity‐frequency, duration, and beverage type. Alcohol consumption throughout pregnancy was explored for craniosynostosis since the period of development may extend beyond the first trimester. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression analysis. OR were adjusted for age, race/ethnicity, and state of residence at time of infant's birth. Gastroschisis OR were also adjusted for periconceptional smoking. RESULTS: Periconceptional alcohol consumption and craniosynostosis showed little evidence of an association (OR = 0.92; CI: 0.78–1.08), but alcohol consumption in the second (OR = 0.65; CI: 0.47–0.92) and third trimesters (OR = 0.68; CI: 0.49–0.95) was inversely associated with craniosynostosis. Periconceptional alcohol consumption was associated with omphalocele (OR = 1.50; CI: 1.15–1.96) and gastroschisis (OR = 1.40; CI: 1.17–1.67). CONCLUSIONS: Results suggest that maternal periconceptional alcohol consumption is associated with omphalocele and gastroschisis, and second and third trimester alcohol consumption are inversely associated with craniosynostosis. Birth Defects Research (Part A) 2011. © 2011 Wiley‐Liss, Inc.     

The CRISPLD2 gene is involved in cleft lip and/or cleft palate in a Chinese population

BACKGROUND: Nonsyndromic cleft lip and/or cleft palate (NSCLP) are common congenital anomalies in humans, the etiologies of which are complex and associated with both genetic and environmental factors. Previous data suggested single nucleotide polymorphisms (SNPs) of rs1546124, rs4783099, and rs16974880 of the CRISPLD2 gene were associated with an increased risk of NSCLP; however, subsequent studies have yielded conflicting results. This study aims to evaluate the associations of the aforementioned polymorphisms with NSCLP in a Northwestern Chinese population. METHODS: Three CRISPLD2 SNPs were genotyped in a case‐control study (n = 907), including 444 NSCLP patients and 463 healthy individuals, using polymerase chain reaction–denaturing high‐performance liquid chromatography (PCR‐DHPLC). RESULTS: The genotype and allele frequencies of rs1546124 (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.58–3.34; p = 1 × 10⁻⁵) and rs4783099 (OR, 0.73; 95% CI, 0.54–1.00; p = 0.05) were different in NSCLP patients compared with controls. Furthermore, the CC genotype at rs1546124 was associated with increased risk for cleft lip with or without cleft palate (CL/P; OR, 2.11; 95% CI, 1.41–3.15; p_correct = 1.5 × 10⁻⁴) and for cleft palate only (CPO; OR, 2.93; 95% CI, 1.69–5.07; p_correct = 5.4 × 10⁻⁴), whereas the T allele of rs4783099 was associated with decreased risk for CPO. Further gender stratification showed that the statistical association of these two loci is mainly in the male patients, and not in female patients. CONCLUSION: Our results suggest that the CRISPLD2 gene contributes to the etiology of NSCLP in the Northwestern Chinese population. SNP rs1546124 is significantly related to NSCLP, associated with both CL/P and CPO groups, and SNP rs4783099 is significantly associated with CPO. Birth Defects Research (Part A) 2011. © 2011 Wiley‐Liss, Inc.     

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.     

Socioeconomic measures,orofacial clefts,and conotruncal heart defects in California

OBJECTIVE : To examine the association of multiple measures of socioeconomic status (SES) with risks of orofacial clefts and conotruncal heart defects. DESIGN : Data were from a recent population‐based case‐control study conducted in California that included 608 patients with orofacial clefts, 277 patients with conotruncal heart defects, and 617 nonmalformed controls. RESULTS : The odds ratio for the worst versus best score on a household‐level SES index was strongest for cleft lip with or without palate, at 1.7 (95% confidence interval, 0.9–3.4); the odds ratios for this comparison were closer to 1 and less precise for the other defect groups. An index based on neighborhood‐level SES was also not associated with increased risk of the studied defects. CONCLUSIONS : This detailed analysis of SES and selected birth defects did not suggest worse SES was associated with increased risk of the studied defects, with the possible exception of cleft lip with or without cleft palate. Birth Defects Research (Part A), 2009. © 2009 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.     

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.     

Maternal fever during early pregnancy and the risk of oral clefts

An increased risk of birth defects after hyperthermic exposures has been confirmed in animal studies, but population studies have yielded inconsistent results. Oral clefts are a common birth defect and have been associated with these exposures in some of these studies. In this study, data from the National Birth Defects Prevention Study was used to evaluate the association of maternal report of febrile illness in early pregnancy and the risk of oral clefts. All oral cleft cases born between 1997 and 2004 were compared with nonmalformed controls born in the same geographical region during the same time period. Mothers reporting febrile illness during pregnancy were stratified by fever grade and antipyretic use. Logistic regression models were used to generate crude and adjusted odds ratios for exposure to fever and association with each oral cleft phenotype. The dataset included 5821 controls, 1567 cases of cleft lip with or without cleft palate (CL+/?P) and 835 cases of cleft palate only. A modestly increased risk was observed for isolated CL+/?P (odds ratio, 1.28; 95% confidence interval, 1.01–1.63). Stratification by fever grade (body temperature <101.5° or ≥101.5°F) did not yield significant differences in risk. Risk estimates were higher among women who reported a fever, but did not take antipyretics to control their fever, particularly for nonisolated compared with isolated oral clefts. This finding suggests that adequate control of fever may diminish the deleterious effects of fever in cases of oral cleft. Birth Defects Research (Part A), 2010. © 2010 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.     

Association between MTHFR polymorphisms and orofacial clefts risk: A meta‐analysis

BACKGROUND The roles of C677T and A1298C polymorphisms in methylenetetrahydrofolate reductase (MTHFR) gene in orofacial clefts (OFCs) risk have been substantially explored, but the results remain conflicting. To address this gap, we conducted a meta‐analysis involving all eligible studies. METHODS: Electronic literature searches of the PubMed, EmBase, and Medline databases were performed up to October 31, 2011. Fixed‐effects or random‐effects models were used to calculate the pooled odds ratios (ORs) for two genetic comparisons (heterozygous mutation vs. wild type, homozygous mutation vs. wild type). RESULTS A total of 18 studies were ultimately identified. The pooled results revealed no statistical association between infant and maternal C677T and A1298C variants and risk of cleft lip with or without palate (CL/P) or cleft palate only (CPO), except for the maternal 677TT genotype for CL/P, the OR was 1.32 (95% confidence interval [CI], 1.06–1.63) as compared to the normal 677CC genotype. In the subgroup analyses on CL/P data based on ethnicity and source of control subjects, almost all of the results were replicated as nonsignificant associations in both examined polymorphisms, whereas the pooled risk estimate calculated for maternal 677TT genotype in the white population remained statistically significant, with an OR of 1.36 (95% CI, 1.05–1.76). CONCLUSIONS This meta‐analysis suggests that maternal MTHFR 677TT genotype might increase the risk of having a CL/P offspring in the white population. However, these findings remain to be confirmed by additional investigations. Birth Defects Research (Part A) 2012. © 2012 Wiley Periodicals, Inc.     

On the symmetry of limb deficiencies among children with multiple congenital anomalies

In humans, unpaired organs are placed in a highly ordered pattern along the left-right axis. As indicated by animal studies, a cascade of signaling molecules establish left-right asymmetry in the developing embryo. Some of the same genes are involved also in limb patterning. To provide a better insight into the connection between these processes in humans, we analysed the symmetry of limb deficiencies among infants with multiple congenital anomalies. The study was based on data collected by the International Clearinghouse for Birth Defects Monitoring Systems (ICBDMS). Registries of the ICBDMS provided information on infants who, in addition to a limb deficiency, also had at least one major congenital anomaly in other organ systems. We reviewed 815 such cases of which 149 cases (18.3 %) were syndromic and 666 (81.7 %) were nonsyndromic. The comparisons were made within the associated limb deficiencies, considering the information on symmetry, using a comparison group with malformations associated not involved in the index association. Among the non-syndromic cases, the left-right distribution of limb deficiencies did not differ appreciably between limb deficiency subtypes (e.g., preaxial, transverse, longitudinal). The left-right distribution of limb anomalies did not differ among most types of non-limb anomalies, though a predominance of left-sided limb deficiencies was observed in the presence of severe genital defects - odds ratio [OR], 2.6; 95 % CI, 1.1-6.4). Limb deficiencies (LDs) were more often unilateral than bilateral when accompanied by gastroschisis (OR, 0.1) or axial skeletal defects (OR, 0.5). On the contrary, LDs were more often bilateral than unilateral when associated with cleft lip with or without cleft palate (OR, 3.9) or micrognathia (OR, 2.6). Specifically, we found an association between bilateral preaxial deficiencies and cleft lip, bilateral amelia with gastroschisis and urinary tract anomalies, and bilateral transverse deficiencies and gastroschisis and axial skeleton defects. Of 149 syndromic cases, 62 (41.6 %) were diagnosed as trisomy 18. Out of the 30 cases of trisomy 18 with known laterality, 20 cases were bilateral. In the remainder the right and left sides were equally affected. Also, in most cases (74.4 %) only the upper limbs were involved. In conclusion the left-right distribution of limb deficiencies among some non-limb anomalies may suggest a relationship between the development of the limb and the left-right axis of the embryo.     

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.     

Maternal urinary tract infections and selected cardiovascular malformations

BACKGROUND: In a population‐based case‐control study, we investigated the association between congenital cardiovascular malformations (CVMs) and maternal urinary tract infections (UTIs). METHODS: Within the National Birth Defects Prevention Study, 3,690 women who had singleton livebirths with nonsyndromic CVMs, and 4,760 women who had infants without birth defects were identified. Affected infants had: conotruncal, septal, anomalous pulmonary venous return, atrioventricular septal defects, or left‐ or right‐sided obstructive heart defects. Mothers had a UTI if they reported having at least one infection during the first trimester. Adjusted ORs and 95% CIs were computed to determine the association between CVMs and UTIs. Stratified analyses were conducted to investigate if sulfonamide use and/or fever modified the effect between CVMs and UTIs. RESULTS: Women who had offspring with either left ventricular outflow tract obstructive defects or atrioventricular septal defects were more likely than controls to report a UTI. These associations remained among women who did not have fever or used sulfonamides. Maternal use of sulfonamides during the UTI did not appear to modify the relationship between CVM subtypes and maternal UTIs. CONCLUSIONS: In the National Birth Defects Prevention Study there was little evidence to support an association between CVMs and UTIs during the first trimester of pregnancy. Associations between left ventricular outflow tract obstructive defects and maternal UTI as well as between atrioventricular septal defects and maternal UTI were found. Our findings, while not conclusive, suggest that the possible association between maternal UTI and CVMs should be investigated further. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.     

Maternal caffeine intake during pregnancy and orofacial clefts

BACKGROUND: Moderate caffeine intake during pregnancy is common, but little is known about its potential association with birth defects. METHODS: The National Birth Defects Prevention Study is a population‐based, case‐control study of major birth defects, excluding infants with single‐gene disorders and chromosomal abnormalities. This analysis includes infants with cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO), excluding infants whose cleft was secondary to holoprosencephaly or amniotic band sequence. Mothers reported dietary caffeine intake from coffee, tea, sodas, and chocolate in the year before pregnancy and reported intake of medications containing caffeine during pregnancy. We assessed the association between dietary caffeine intake, frequency of consuming each type of caffeinated beverage, medications containing caffeine, and CL/P or CPO among infants born from October 1997 through December 2004. RESULTS: This analysis included 1531 infants with CL/P, 813 infants with CPO, and 5711 infants with no major birth defects (controls). Examining dietary sources among control mothers, 11% reported consuming at least 300 mg of caffeine per day and 17% reported consuming less than 10 mg of caffeine per day; high consumption (≥3 servings per day) was reported by 8% (coffee), 4% (tea), and 15% (sodas); medications containing at least 100 mg caffeine/dose were reported by less than 1%. Although some effect estimates were elevated for moderate caffeine intake from all beverages, estimates were closer to the null for high caffeine levels. Isolated CL/P was associated with use of medications containing at least 100 mg of caffeine per dose. CONCLUSIONS: Our data do not suggest an association between maternal dietary caffeine intake and orofacial clefts, but caffeine‐containing medications merit further study. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.