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.     

Integration of DNA sample collection into a multi-site birth defects case-control study

BACKGROUND: Advances in quantitative analysis and molecular genotyping have provided unprecedented opportunities to add biological sampling and genetic information to epidemiologic studies. The purpose of this article is to describe the incorporation of DNA sample collection into the National Birth Defects Prevention Study (NBDPS), an ongoing case-control study in an eight-state consortium with a primary goal to identify risk factors for birth defects. METHODS: Babies with birth defects are identified through birth defects surveillance systems in the eight participating centers. Cases are infants with one or more of over 30 major birth defects. Controls are infants without defects from the same geographic area. Epidemiologic information is collected through an hour-long interview with mothers of both cases and controls. We added the collection of buccal cytobrush DNA samples for case-infants, control-infants, and their parents to this study. RESULTS: We describe here the methods by which the samples have been collected and processed, establishment of a centralized resource for DNA banking, and quality control, database management, access, informed consent, and confidentiality issues. CONCLUSIONS: Biological sampling and genetic analyses are important components to epidemiologic studies of birth defects aimed at identifying risk factors. The DNA specimens collected in this study can be used for detection of mutations, study of polymorphic variants that confer differential susceptibility to teratogens, and examination of interactions among genetic risk factors. Information on the methods used and issues faced by the NBDPS may be of value to others considering the addition of DNA sampling to epidemiologic studies.     

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.     

Clinician reviewers in birth defects surveillance programs: survey of the National Birth Defects Prevention Network

BACKGROUND: Some birth defects surveillance programs utilize a clinician reviewer ("Clinician") to assist the multidisciplinary staff in the process of case review, coding and classification. The untested assumption is that expertise in the evaluation of individuals with birth defects and genetic syndromes in clinical practice, usually clinical genetics, is useful in reviewing medical records. METHODS: We conducted an exploratory survey of the 50 functioning birth defects surveillance programs that participated in the National Birth Defects Prevention Network in 2004. The survey was mailed electronically to program coordinators and included 10 questions with check-off option replies. Open-ended comments were also solicited. RESULTS: Responses were received from 31 of 50 (62%) programs, 21 (68%) which used a Clinician. In addition to the 9 centers that identified themselves as participants in the National Birth Defects Prevention Study (NBDPS), there were 12 non-NBDPS programs using a Clinician, 2 of whom were not clinical geneticists (1 nurse genetic counselor and 1 primary pediatrician). A total of 86% (18/21) of Clinicians were employed part-time or as consultants; 1 was full-time, and 2 were volunteers. In addition to the core activities of classifying defects and reviewing cases to determine if a syndrome was present, over one-half of the Clinicians participated in education of birth defects surveillance programs staff, research, and program development. Most (86%; 18/21) Clinicians had been trained informally for their roles. Only 1 had received a formal performance review. CONCLUSIONS: Aside from the 9 centers in the NBDPS in which the position of Clinician is funded by the Centers for Disease Control and Prevention (CDC), about one-half of the remaining respondent birth defects surveillance programs used a Clinician. Future research is needed to determine why a birth defects surveillance program hires or refrains from using a Clinician, and whether a Clinician accomplishes the desired goals. This survey reveals a lack of formal training for the Clinicians in their roles in the surveillance programs, and a lack of quality monitors, which might be addressed in the future.     

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.     

Maternal occupational exposure to polycyclic aromatic hydrocarbons and congenital heart defects among offspring in the national birth defects prevention study

BACKGROUND: There is evidence in experimental model systems that exposure to polycyclic aromatic hydrocarbons (PAHs) results in congenital heart defects (CHDs); however, to our knowledge, this relationship has not been examined in humans. Therefore, we conducted a case‐control study assessing the association between estimated maternal occupational exposure to PAHs and CHDs in offspring. METHODS: Data on CHD cases and control infants were obtained from the National Birth Defects Prevention Study for the period of 1997 to 2002. Exposure to PAHs was assigned by industrial hygienist consensus, based on self‐reported maternal occupational histories from 1 month before conception through the third month of pregnancy. Logistic regression was used to evaluate the association between maternal occupational PAH exposure and specific CHD phenotypic subtypes among offspring. RESULTS: The prevalence of occupational PAH exposure was 4.0% in CHD case mothers (76/1907) and 3.6% in control mothers (104/2853). After adjusting for maternal age, race or ethnicity, education, smoking, folic acid supplementation, and study center, exposure was not associated with conotruncal defects (adjusted odds ratio [AOR], 0.98; 95% confidence interval [CI], 0.58–1.67), septal defects (AOR, 1.28; 95% CI, 0.86–1.90), or with any isolated CHD subtype. CONCLUSIONS: Our findings do not support an association between potential maternal occupational exposure to PAHs and various CHDs in a large, population‐based study. For CHD phenotypic subtypes in which modest nonsignificant associations were observed, future investigations could be improved by studying populations with a higher prevalence of PAH exposure and by incorporating information on maternal and fetal genotypes related to PAH metabolism. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.     

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.     

Exposure to non-steroidal anti-inflammatory drugs during pregnancy and the risk of selected birth defects: a prospective cohort study

Background

Since use of non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy is common, small increases in the risk of birth defects may have significant implications for public health. Results of human studies on the teratogenic risks of NSAIDs are inconsistent. Therefore, we evaluated the risk of selected birth defects after prenatal exposure to prescribed and over-the-counter NSAIDs.

Methods and Findings

We used data on 69,929 women enrolled in the Norwegian Mother and Child Cohort Study between 1999 and 2006. Data on NSAID exposure were available from a self-administered questionnaire completed around gestational week 17. Information on pregnancy outcome was obtained from the Medical Birth Registry of Norway. Only birth defects suspected to be associated with NSAID exposure based upon proposed teratogenic mechanisms and previous studies were included in the multivariable logistic regression analyses. A total of 3,023 women used NSAIDs in gestational weeks 0–12 and 64,074 women did not report NSAID use in early pregnancy. No associations were observed between overall exposure to NSAIDs during pregnancy and the selected birth defects separately or as a group (adjusted odds ratio 0.7, 95% confidence interval 0.4–1.1). Associations between maternal use of specific types of NSAIDs and the selected birth defects were not found either, although an increased risk was seen for septal defects and exposure to multiple NSAIDs based on small numbers (2 exposed cases; crude odds ratio 3.9, 95% confidence interval 0.9–15.7).

Conclusions

Exposure to NSAIDs during the first 12 weeks of gestation does not seem to be associated with an increased risk of the selected birth defects. However, due to the small numbers of NSAID-exposed infants for the individual birth defect categories, increases in the risks of specific birth defects could not be excluded.     

Prevalence and patterns of nitrosatable drug use among U.S. women during early pregnancy

BACKROUND

Experimental evidence indicates that certain drugs, that are secondary or tertiary amines or amides, form N‐nitroso compounds in the presence of nitrite in an acidic environment. Nitrosatable drugs have been associated with birth defects in a few epidemiologic studies. This study describes the prevalence and patterns of nitrosatable drug use among U.S. women during early pregnancy and examines maternal factors associated with such use.

METHODS

Data were analyzed from the National Birth Defects Prevention Study and included 6807 mothers who gave birth to babies without major congenital malformations during 1997 to 2005. Information was collected by telephone interview about medication use, demographic factors, and maternal health. Drugs taken during the first trimester were classified according to nitrosatability, amine and amide functional groups, and primary indication of use.

RESULTS

Approximately 24% of the women took one or more nitrosatable drugs during the first trimester, including 12.4%, 12.2%, and 7.6% who respectively took secondary amines, tertiary amines, or amides. Five of the ten most commonly taken drugs were available over the counter. Women who were non‐Hispanic white (29.5%), with 1 year or more college education (27.3%) or 40 years or older (28.8%) had the highest prevalence of use. Supplemental vitamin C, an inhibitor of nitrosation, was not taken by 41.6% and 19.3% of nitrosatable drug users during the first and second months of pregnancy, respectively.

CONCLUSIONS

In this U.S. population, ingestion of drugs classified as nitrosatable was common during the first trimester of pregnancy, especially among non‐Hispanic white, more educated, and older mothers. Birth Defects Research (Part A) 2011. © 2011 Wiley‐Liss, Inc.     

Characteristics that predict locating and interviewing mothers identified by a state birth defects registry and vital records

BACKGROUND: State vital records are often used to select population-based controls in record-linkage studies of birth defects. However, locating and contacting individuals based on these data sources to collect additional data can be a challenge. METHODS: A large case-control study of air quality and birth defects was conducted in 7 Texas counties in which cases were selected from the Texas Birth Defects Registry and controls from state vital records. In 2004, data from these sources were used to trace mothers of cases and controls who delivered babies in the year 2000 (n=2477) for participation in a computer-assisted telephone interview. A number of factors that predicted whether an individual would be located and interviewed were identified. RESULTS: Between March and August 2004, 38% of the mothers were located, and 38% of the located mothers were interviewed. Case mothers were more likely than control mothers to be located (44 vs. 30%) and, if located, to be interviewed (43 vs. 31%). We compared the characteristics of mothers who were not located (case n=760; control n=777), mothers who were located but not interviewed (case n=344; control n=236), and mothers who were interviewed (case n=256; control n=104). Among both cases and controls, older mothers (>or=30 years) were more likely than younger mothers to be located, and non-Hispanic black mothers were least likely to be located and interviewed. CONCLUSIONS: Despite the utility of vital records as a source of population-based controls in record-linkage analyses, the poor response rate discourages the use of these data sources to contact individuals for a follow-up study 4 years after delivery.     

Evaluation of birth defect histories obtained through maternal interviews.

Etiologic studies of birth defects often use family history information provided by parents of patients. The validity of this information has not been adequately assessed. Using data from the Atlanta Birth Defects Case-Control study, we evaluated sensitivity, specificity, and positive predictive value of mothers' responses regarding the presence of birth defects in their offspring. A total of 4929 mothers of infants with major structural defects ascertained by the Metropolitan Atlanta Congenital Defects Program and a total of 3,029 mothers of normal infants were asked whether their babies had had a birth defect or a health problem diagnosed during the first year of life. Interviewers and coders of maternal responses were blinded to the case-control status of infants. Sensitivity (the proportion of case mothers who gave responses that could be coded as denoting a major birth defect) was 61%. Specificity (the proportion of control mothers who gave responses that could not be coded as denoting a major birth defect) was 98%. The positive predictive value (the proportion of mothers who gave a major-birth-defect response who in fact had babies with major birth defects) was estimated as 47%. Sensitivity, specificity, and positive predictive value varied by maternal sociodemographic factors such as race and education, as well as by type of defect. These results suggest that family history data obtained through maternal interviews should be cautiously interpreted and, if not properly validated, may alter estimates of recurrence risks.     

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.     

Ascertainment of pregnancies terminated because of birth defects: effect on completeness of adding a new source of data

BACKGROUND: When evaluating preventive programs such as folate promotion and rubella vaccination, it is critically important to include terminations of pregnancy for neural tube defects and congenital rubella syndrome. Data from birth defects registries are often used for this purpose. The Western Australian Birth Defects Registry ascertains cases of birth defects in livebirths, stillbirths, and terminations of pregnancy for fetal abnormality, using multiple sources of ascertainment. METHODS: Data on terminations of pregnancy for fetal abnormality from the Western Australian Hospital Morbidity Data System 1980-1997 (not previously available to the Registry) were used to estimate the completeness of ascertainment of such cases by the Registry. Ascertainment-adjusted prevalences were calculated using capture-recapture methods. RESULTS: A total of 702 terminations with birth defects were identified among hospital discharges, most of which were already known to the Registry (87.9%). Of the 85 new cases, seven had a neural tube defect, 23 had a chromosomal defect, and 12 had confirmed maternal rubella infection during pregnancy. The ascertainment-adjusted prevalence was not importantly [corrected] different for birth defects overall or for these individual conditions, although the 95% confidence intervals for all birth defects, and for all chromosomal defects, did not include the prevalence based on registered cases only. CONCLUSIONS: The Western Australian Birth Defects Registry ascertains a high proportion of pregnancies terminated for fetal abnormality, and should therefore be a reliable source of data with which to assist in monitoring the effectiveness of preventive programs.     

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.     

Linking teratogen information service and birth defects registry databases to improve knowledge of birth defect status

BACKGROUND: Although teratogen information services (TISs) obtain maternal exposure information from their callers, such services often do not know if the pregnancies were affected by a birth defect. This study attempted to improve the completeness of this information for Texas Teratogen Information Service (TTIS) callers by linking their records with the Texas Birth Defects Registry (TBDR) and Texas birth certificates (TBCs). METHODS: A total of 344 expectant mothers called TTIS with expected dates of delivery between 1 January 2000 and 31 December 2001. These pregnancies were linked with TBDR and TBC data. The percentages of pregnancies with known birth defect information both before and after the linkage were compared. RESULTS: The TTIS originally collected birth defect status information for 101 of the 344 callers (29.4%) and 0.6% of all 344 callers or 2.0% of callers with birth defect status information had a pregnancy affected by a birth defect. Linking TTIS records with TBDR and TBC data helped to raise the percentage of callers with birth defect status information from 29.4% to 71.5%. Among those callers, the percentage known to have birth defects increased from 2.0% to 4.1%. The sensitivity of TTIS follow-up calls in identifying birth defects was 50%, and the specificity was 100%. CONCLUSIONS: Linking TTIS caller records with TBDR and TBC data significantly increased both the percentage of pregnancies with birth defect status information and the percentage of pregnancies identified as affected by birth defects. Such linkage may be a good approach by which TISs can increase the completeness of their birth defect status information.     

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.     

A case–control study of the effects of pregnancy planning on neural tube defects and its primary preventive measures

BACKGROUND: Measures for prevention of neural tube defects (NTDs) have been recommended for many years in China, but the compliance with these measures is unsatisfactory. This study aims to compare the effect differences between planned pregnancy and unplanned pregnancy in the compliance with these measures and analyze the interactions between pregnancy planning and these measures for NTD prevention. METHODS: A 1:1 matched case‐control study was conducted. We randomly selected 349 women who delivered or gestated babies/fetuses with NTDs in the last two years in two provinces and matched them with 349 women who delivered babies without obvious birth defects as controls. RESULTS: In the case group, 99 women reported that they had planned their pregnancies, accounting for 28.4%, and the proportion who received preconception examinations and took folic acid prior to conception was 13.8 and 8.6%, respectively. According to the multivariate analysis, health education (odds ratio [OR], 0.350), preconception examinations (OR, 0.497) and folic acid consumption prior to conception (OR, 0.257) all had preventative effects on NTDs (for all, p < 0.05). In both groups, the proportions of women who received preconception examinations and reported folic acid intake were much higher for those who reported planning their pregnancies compared to women with an unplanned pregnancy (for all, p < 0.01); and for NTD prevention, synergistic interactions existed between pregnancy planning and the other preventive measures. CONCLUSION: Folic acid consumption prior to conception, preconception examinations, and health education have preventive effects on NTDs. Pregnancy planning can significantly promote compliance with these preventive behaviors. In addition, there are synergistic interactions between pregnancy planning and these measures. Birth Defects Research (Part A), 2010. © 2010 Wiley‐Liss, Inc.     

National estimates and race/ethnic-specific variation of selected birth defects in the United States, 1999-2001

BACKGROUND: In the United States, birth defects affect approximately 3% of all births, are a leading cause of infant mortality, and contribute substantially to childhood morbidity. METHODS: Population-based data from the National Birth Defects Prevention Network were combined to estimate the prevalence of 21 selected defects for 1999-2001, stratified by surveillance system type. National prevalence was estimated for each defect by pooling data from 11 states with active case-finding, and adjusting for the racial/ethnic distribution of US live births. We also assessed racial/ethnic variation of the selected birth defects. RESULTS: National birth defect prevalence estimates ranged from 0.82 per 10,000 live births for truncus arteriosus to 13.65 per 10,000 live births for Down syndrome. Compared with infants of non-Hispanic (NH) white mothers, infants of NH black mothers had a significantly higher birth prevalence of tetralogy of Fallot, lower limb reduction defects, and trisomy 18, and a significantly lower birth prevalence of cleft palate, cleft lip with or without cleft palate, esophageal atresia/tracheoesophageal fistula, gastroschisis, and Down syndrome. Infants of Hispanic mothers, compared with infants of NH white mothers, had a significantly higher birth prevalence of anencephalus, spina bifida, encephalocele, gastroschisis, and Down syndrome, and a significantly lower birth prevalence of tetralogy of Fallot, hypoplastic left heart syndrome, cleft palate without cleft lip, and esophageal atresia/tracheoesophageal fistula. CONCLUSIONS: This study can be used to evaluate individual state surveillance data, and to help plan for public health care and educational needs. It also provides valuable data on racial/ethnic patterns of selected major birth defects.     

Fine particle‐induced birth defects: Impacts of size,payload, and beyond

Worldwide epidemiological studies have shown that exposures to particulate matters (PMs), such as PM_2.5 or PM₁₀, during pregnancy cause birth defects in the newborn. Although mechanistic understanding of such effects are not available, recent research using murine models highlights some key progress: (1) toxicity caused by PMs is a combined effects of particles and the adsorbed toxic pollutants, such as heavy metals, persistent organic pollutants, bacteria, and virus. Fine particles may hold on to pollutants and, therefore, reduce their toxicity or enhance the toxicity by carrying pollutants crossing the placental barrier; (2) smaller size, certain particle surface chemistry modifications, early developmental stage of placenta, and maternal diseases all aggravate PM‐induced birth defects; (3) molecular events involved in such toxicity are begin to emerge: induction of oxidative stress, DNA damage, and alteration of molecular signaling or epigenetic events are some possible causes. Despite this progress, a clear understanding of PM‐induced birth defects awaits further breakthroughs on many fronts, including epidemiological studies, animal models, nanotoxicity, and molecular mechanism investigations. Birth Defects Research (Part C) 108:196–206, 2016. © 2016 Wiley Periodicals, Inc.