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.     

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.     

Prevalence of periconceptional folic acid use and perceived barriers to the postgestation continuance of supplemental folic acid: survey results from a Teratogen Information Service

BACKGROUND: Fewer than 40% of U.S. women are taking folic acid supplements periconceptionally at a time when the risk of neural tube defects (NTDs) can be reduced by supplementation. A better understanding of the vitamin-taking habits of childbearing-age women and effective methods for improving periconceptional supplement use are needed. METHODS: A telephone survey conducted through the California Teratogen Information Service (TIS) between August 2003 and January 2004 assessed the prevalence and characteristics of pregnant callers who did not use folic acid supplements in the periconceptional period, and explored attitudes toward advice to continue vitamin use following pregnancy in order to be protected in a future pregnancy. RESULTS: A total of 327 pregnant women who called the TIS for information agreed to participate in the survey. More than half (53.2%) were not taking folic acid-containing supplements in the periconceptional period. Predictors of lack of use included a higher prepregnancy body mass index, younger maternal age, non-white race/ethnicity, lower education level, and unplanned pregnancy. One-quarter of the women said they would be willing to continue taking vitamins after the pregnancy if advised to do so by a physician. The remainder identified obstacles to following that advice--notably, not planning to become pregnant again and the belief that enough folate is derived from diet alone. CONCLUSIONS: More than half of the callers to the TIS were not compliant with recommendations regarding periconceptional folic acid supplementation. This represents an opportunity for TIS specialists and physicians to intervene in a current pregnancy to encourage maintenance of supplement use in the subsequent interpregnancy interval.     

Prevention of NTDs with periconceptional multivitamin supplementation containing folic acid in China

BACKGROUND: Maternal nutritional factors seem to contribute substantially to the complex etiologies of NTDs. Foremost among these factors is the periconceptional use of supplementation containing folic acid, which is associated with a reduction in the risk of women having NTD‐affected pregnancies. This study was designed to observe the effectiveness of multivitamin supplementation containing folic acid in preventing NTDs in a Chinese population and to detect factors that would impact the effectiveness. METHODS: Through family planning networks, a population‐based community intervention study was carried out in 18 counties of China. Participants were divided into an intervention (taking multivitamin) group and a control group, and were followed up according to periconceptional multivitamin supplementation (in general 6 mg) for 2 years. Women who had a pregnancy were followed up from 28 weeks gestation at least to pregnancy termination, and the outcome was recorded. The incidence rate of the two groups and the relative risks were calculated to evaluate the efficacy of the multivitamin supplement in preventing NTDs. RESULTS: During 2000 and 2002, all of the women having pregnancies with birth defects and women whose pregnancies were without any birth defects were interviewed. Nine NTDs were recorded from 25,444 pregnancies (NTD birth prevalence = 0.35/1,000 pregnancies) in the intervention group and 48 NTDs among 26,599 pregnancies (NTD birth prevalence = 1.80/1,000 pregnancies) in the control group. The protective rate was 80.4%. CONCLUSIONS: Periconceptional multivitamin supplementation containing folic acid can prevent the occurrence of NTDs with the beneficial effect dependent on the frequency and timing of the supplementation. Our study suggests that multivitamin supplement containing folic acid taken from a time point of 2 months before conception and continuing until completion of the second month after conception and taken more than five times per week can significantly reduce the risks of NTDs. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.     

Early pregnancy agricultural pesticide exposures and risk of gastroschisis among offspring in the San Joaquin Valley of California

Background: Prevalence of gastroschisis has inexplicably been increasing over the past few decades. Our intent was to explore whether early gestational exposures to pesticides were associated with risk of gastroschisis. Methods: We used population‐based data, accompanied by detailed information from maternal interviews as well as information on residential proximity to a large number of commercial pesticide applications during early pregnancy. The study population derived from the San Joaquin Valley of California ( ). Cases were 156 infants/fetuses with gastroschisis and controls were 785 infants without birth defects. Results: Among 22 chemical pesticide groups analyzed, none had an elevated odds ratio with an associated confidence interval that excluded 1.0, although exposure to the triazine group showed borderline significance. Among 36 specific pesticide chemicals analyzed, only exposure to petroleum distillates was associated with an elevated risk, odds ratio = 2.5 (1.1–5.6). In general, a substantially different inference was not derived when analyses were stratified by maternal age or when risk estimation included adjustment for race/ethnicity, body mass index, folic acid supplement use, and smoking. Conclusion: Our study rigorously adds to the scant literature on this topic. Our a priori expectation was that we would observe certain pesticide compounds to be particularly associated with young age owing to the disproportionate risk observed for young women to have offspring with gastroschisis. We did not observe an exposure profile unique to young women. Birth Defects Research (Part A), 100:686–694, 2014. © 2014 Wiley Periodicals, 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.     

Neural tube defects,folate, and immune modulation

Periconceptional supplementation with folic acid has led to a significant worldwide reduction in the incidence of neural tube defects (NTDs). However, despite increasing awareness of the benefits of folic acid supplementation and the implementation of food fortification programs in many countries, NTDs continue to be a leading cause of perinatal morbidity and mortality worldwide. Furthermore, there exists a significant subgroup of women who appear to be resistant to the protective effects of folic acid supplementation. The following review addresses emerging clinical and experimental evidence for a role of the immune system in the etiopathogenesis of NTDs, with the aim of developing novel preventative strategies to further reduce the incidence of NTD‐affected pregnancies. In particular, recent studies demonstrating novel roles and interactions between innate immune factors such as the complement cascade, neurulation, and folate metabolism are explored. Birth Defects Research (Part A) 97:602–609, 2013. © 2013 Wiley Periodicals, Inc.     

No major role for periconceptional folic acid use and its interaction with the MTHFR C677T polymorphism in the etiology of congenital anorectal malformations

Background: Both genetic and nongenetic factors are suggested to be involved in the etiology of congenital anorectal malformations (ARM). Maternal periconceptional use of folic acid supplements were inconsistently suggested to play a role in the prevention of ARM. Therefore, we investigated independent associations and interactions of maternal periconceptional folic acid supplement use and the infant and maternal MTHFR (methylenetetrahydrofolate reductase) C677T polymorphisms with the risk of ARM and subgroups of ARM. Methods: A case–control study was conducted among 371 nonsyndromic ARM cases and 714 population‐based controls born between 1990 and 2012 using maternal questionnaires and DNA samples from mother and child. Cases were treated for ARM at departments of Pediatric Surgery of the Radboud university medical center, Sophia Children's Hospital‐Erasmus MC Rotterdam, and the University Medical Center Groningen in The Netherlands and hospitals throughout Germany. Results: No association with folic acid use was present (odds ratio = 1.1; 95% confidence interval: 0.8–1.4) for ARM as a group. Infant and maternal MTHFR C677T polymorphisms were weakly associated with isolated ARM in particular. Lack of folic acid supplement use in combination with infants or mothers carrying the MTHFR C677T polymorphism did not seem to increase the risk of ARM or subgroups of ARM. The relative excess risks due to interaction did not clearly indicate interaction on an additive scale either. Conclusion: This first study investigating interactions between periconceptional folic acid supplement use and infant and maternal MTHFR C677T polymorphisms in the etiology of ARM did not provide evidence for a role of this gene–environment interaction. Birth Defects Research (Part A) 100:483–492, 2014. © 2014 Wiley Periodicals, Inc.     

Trends in the postfortification prevalence of spina bifida and anencephaly in the United States

BACKGROUND: The prevalence of NTDs in the US declined significantly after mandatory folic acid fortification; however, it is not known if the prevalence of NTDs has continued to decrease in recent years relative to the period immediately following the fortification mandate. METHODS: Population‐based data from 21 birth defects surveillance systems were used to examine trends in the birth prevalence of spina bifida and anencephaly during 1999–2000, 2001–2002, and 2003–2004. Prevalence data were stratified by non‐Hispanic White, non‐Hispanic Black, and Hispanic race or ethnicity. Prevalence ratios were calculated by dividing the birth prevalences during the later time periods (2001–2002 and 2003–2004) by the birth prevalences during 1999–2000. RESULTS: During 1999–2004, 3,311 cases of spina bifida and 2,116 cases of anencephaly were reported. Hispanic infants had the highest prevalences of NTDs for all years. For all infants, the combined birth prevalences of spina bifida and anencephaly decreased 10% from the 1999–2000 period to the 2003–2004 period. The decline in spina bifida (3%) was not significant; however the decline in anencephaly (20%) was statistically significant. CONCLUSIONS: While the prevalences of spina bifida and anencephaly in the United States have declined since folic acid fortification in the food supply began, these data suggest that reductions in the prevalence of anencephaly continued during 2001–2004 and that racial and ethnic and other disparities remain. Birth Defects Research (Part A), 2008. © 2008 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.     

Epidemiology of nonsyndromic conotruncal heart defects in Texas, 1999-2004

INTRODUCTION: Congenital heart defects (CHDs) are the most common structural birth defects, yet their etiology is poorly understood. As there is heterogeneity within the group of CHDs, epidemiologic studies often focus on subgroups, of conditions, such as conotruncal heart defects (CTDs). However, even within these subgroups there may be etiologic heterogeneity. The aim of the present study was to identify and compare maternal and infant characteristics associated with three CTDs: truncus arteriosus (TA), dextro‐transposition of the great arteries (d‐TGA), and tetralogy of Fallot (TOF). METHODS: Data for cases with nonsyndromic TA (n = 78), d‐TGA (n = 438), and TOF (n = 529) from the Texas Birth Defects Registry, 1999–2004, were used to estimate crude and adjusted prevalence ratios, separately for each condition, using Poisson regression. Polytomous logistic regression was used to determine whether the observed associations were similar across the two largest case groups (d‐TGA and TOF). RESULTS: In Texas, 1999–2004, the prevalence of nonsyndromic TA, d‐TGA, and TOF was 0.35, 1.98, and 2.40 per 10,000 live births, respectively. There was evidence of a significant linear increase in the risk of each condition with advancing maternal age (p < 0.01). Significant associations were observed for TA and maternal residence on the Texas‐Mexico border; d‐TGA and infant sex, maternal race/ethnicity, history of previous live birth, and birth year; and TOF and maternal race/ethnicity and education. Further, the associations with some, but not all, of the study variables were significantly different for d‐TGA and TOF. CONCLUSION: These findings add to our limited understanding of the epidemiology of CTDs. Birth Defects Research (Part A), 2010. © 2010 Wiley‐Liss, Inc.     

Use of multivitamins and folic acid in early pregnancy and multiple births in Sweden.

Folic acid is recommended to reduce the risk of neural tube defects and other congenital malformations. Data from the Swedish Medical Birth Registry were used to study frequency of twinning in women who in early pregnancy reported the use of folic acid. Women (n = 2,569) who in early pregnancy reported the use of folic acid had an increased rate of twin deliveries after consideration of maternal age and of length of involuntary childlessness, both variables being significant confounders. The effect of folic acid was seen also in women who did not report involuntary childlessness. A similar but not statistically significant trend was seen after use of multivitamins without simultaneous use of folic acid tablets (n = 1,979). The increased risk seems to be limited to dizygotic twinning (relative risk = 2.13, 95% CI 1.64-2.74). If this association is causal, wide-spread supplementation with folic acid may represent a hazard larger than the postulated beneficial effect on neural tube defects, at least in low-risk areas.     

Moderately high intake of folic acid has a negative impact on mouse embryonic development

BACKGROUND

The incidence of neural tube defects has diminished considerably since the implementation of food fortification with folic acid (FA). However, the impact of excess FA intake, particularly during pregnancy, requires investigation. In a recent study, we reported that a diet supplemented with 20‐fold higher FA than the recommended intake for rodents had adverse effects on embryonic mouse development at embryonic days (E)10.5 and 14.5. In this report, we examined developmental outcomes in E14.5 embryos after administering a diet supplemented with 10‐fold higher FA than recommended to pregnant mice with and without a mild deficiency of methylenetetrahydrofolate reductase (MTHFR).

METHODS

Pregnant mice with or without a deficiency in MTHFR were fed a control diet (recommended FA intake of 2 mg/kg diet for rodents) or an FA‐supplemented diet (FASD; 10‐fold higher than the recommended intake [20 mg/kg diet]). At E14.5, mice were examined for embryonic loss and growth retardation, and hearts were assessed for defects and for ventricular wall thickness.

RESULTS

Maternal FA supplementation was associated with embryonic loss, embryonic delays, a higher incidence of ventricular septal defects, and thinner left and right ventricular walls, compared to mothers fed control diet.

CONCLUSIONS

Our work suggests that even moderately high levels of FA supplementation may adversely affect fetal mouse development. Additional studies are warranted to evaluate the impact of high folate intake in pregnant women. Birth Defects Research (Part A), 2013. © 2012 Wiley Periodicals, Inc.     

Anencephaly and spina bifida among Hispanics: Maternal,sociodemographic, and acculturation factors in the National Birth Defects Prevention Study

BACKGROUND : We used data from the multisite National Birth Defects Prevention Study for expected delivery dates from October 1997 through 2003, to determine whether the increased risk in anencephaly and spina bifida (neural tube defects (NTDs)) in Hispanics was explained by selected sociodemographic, acculturation, and other maternal characteristics. METHODS : For each type of defect, we examined the association with selected maternal characteristics stratified by race/ethnicity and the association with Hispanic parents' acculturation level, relative to non‐Hispanic whites. We used logistic regression and calculated crude odds ratios (ORs) and their 95% confidence intervals (CIs). RESULTS : Hispanic mothers who reported the highest level of income were 80% less likely to deliver babies with spina bifida. In addition, highly educated Hispanic and white mothers had 76 and 35% lower risk, respectively. Other factors showing differing effects for spina bifida in Hispanics included maternal age, parity, and gestational diabetes. For spina bifida there was no significant elevated risk for U.S.–born Hispanics, relative to whites, but for anencephaly, corresponding ORs ranged from 1.9 to 2.3. The highest risk for spina bifida was observed for recent Hispanic immigrant parents from Mexico or Central America residing in the United States <5 years (OR = 3.28, 95% CI = 1.46–7.37). CONCLUSIONS : Less acculturated Hispanic parents seemed to be at highest risk of NTDs. For anencephaly, U.S.–born and English‐speaking Hispanic parents were also at increased risk. Finally, from an etiologic standpoint, spina bifida and anencephaly appeared to be etiologically heterogeneous from these analyses. Birth Defects Research (Part A), 2009. © 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.     

Proportion of neural tube defects attributable to known risk factors

BACKGROUND

Recognized risk factors for neural tube defects (NTDs) poorly predict population‐level NTD risk. However, the proportion of NTDs that can be attributed to these risk factors is uncertain.

METHODS

To determine the proportion of NTD cases that is attributable to known or suspected risk factors (i.e., female infant sex, family history of NTDs, and maternal Hispanic ethnicity, obesity, pregestational diabetes, gestational diabetes, low dietary folate intake, lack of folic acid supplementation, anticonvulsant use, and hot tub or sauna use), we estimated the adjusted population attributable fraction (aAF) for each factor, using the method of Eide and Geffler and data from the National Birth Defects Prevention Study.

RESULTS

Our analyses of these data indicate that the proportion of cases of spina bifida and anencephaly that can be attributed to known risk factors is 28% and 44%, respectively. For spina bifida, the factor with the greatest attributable fraction was maternal obesity (aAF, 10%), whereas for anencephaly it was Hispanic ethnicity (aAF, 15%).

CONCLUSION

Our analyses indicate that known risk factors account for <50% of NTD cases. Hence, the majority of NTD cases are attributable to, as yet, unidentified factors. These findings highlight the need for continued research to identify genetic and additional nongenetic risk factors for NTDs. Further, these findings suggest that strategies that aim to reduce the risk of NTDs associated with maternal Hispanic ethnicity and obesity may have the greatest impact on the population prevalence of these conditions. Birth Defects Research (Part A), 2013. © 2012 Wiley Periodicals, Inc.     

Common congenital anomalies: Environmental causes and prevention with folic acid containing multivitamins

Congenital anomalies, congenital defects, or birth defects are significant causes of death in infants. The most common congenital defects are congenital heart defects (CHDs) and neural tube defects (NTDs). Defects induced by genetic mutations, environmental exposure to toxins, or a combination of these effects can result in congenital malformations, leading to infant death or long‐term disabilities. These defects produce significant mortality and morbidity in the affected individuals, and families are affected emotional and financially. Also, society is impacted on many levels. Congenital anomalies may be reduced by dietary supplements of folic acid and other vitamins. Here, we review the evidence for specific roles of toxins (alcohol, cigarette smoke) in causing common severe congenital anomalies like CHDs, NTDs, and ocular defects. We also review the evidence for beneficial effects for dietary supplementation, and highlight gaps in our knowledge, where research may contribute to additional benefits of intervention that can reduce birth defects. Extensive discussion of common severe congenital anomalies (CHDs, NTDs, and ocular defects) illustrates the effects of diet on the frequency and severity of these defects. Birth Defects Research (Part C) 108:274–286, 2016. © 2016 Wiley Periodicals, Inc.     

Folate concentrations and folic acid supplementation among women in their first trimester of pregnancy in a rural area with a high prevalence of neural tube defects in Shanxi, China

BACKGROUND: Although an information campaign concerning periconceptional folic acid supplementation was launched in 1998 in Shanxi Province, China, the prevalence of neural tube defects in rural areas was reported as high as 140 per 10,000 births in 2002. The blood folate concentrations and the practice of folic acid supplementation among pregnant women in rural areas of the province are described. METHODS: A total of 483 pregnant women (mean gestation, 8.1 weeks) in a rural area of Shanxi were interviewed. Nonfasting blood samples and information on folic acid supplementation were collected. Folate concentrations in plasma and erythrocytes were determined by a microbiological assay. RESULTS: The mean concentrations of plasma and erythrocyte folate for pregnant women was 10.4 nmol/liter and 375.8 nmol/liter, respectively. Deficiencies of plasma and erythrocyte folate were observed in 20.9% and 47.6% of women, respectively. Seasonal variations were noted in the prevalence of folate deficiency, with significantly lower plasma folate concentrations in spring and summer and lower erythrocyte folate concentrations in seasons other than summer. Among pregnant women, <10% reported having taken or currently taking folic acid, and virtually no women (0.6%) took folic acid as recommended. CONCLUSIONS: Women in rural areas had low plasma and erythrocyte folate levels, and folate deficiency was highly prevalent in the area. Few women followed the recommendations regarding folic acid supplementation, and the information campaign in Shanxi was unsuccessful. These findings suggest the urgent need for combined strategies in rural areas to fortify grain with folic acid and promote folic acid supplements for childbearing-age women.     

备孕二胎女性人群中MTHFR基因多态性及相关环境因素的调查分析

目的:调查评估备孕二胎女性人群中MTHFR基因多态性及其生活习惯、一胎孕期情况等相关环境因素,以发挥孕前检查在子代先心病一级预防中的作用。方法:选取江苏部分地区参加备孕二胎优生健康检查妇女共402名进行问卷调查,并检测外周血中MTHFR基因rs1801131、rs1801133两个位点的突变情况。结果:收回有效问卷389份,其中备孕二胎女性平均年龄为27.04±2.68,最大43岁,最小19岁。MTHFR rs1801131纯合突变(CC型)为3.5%、杂合突变(AC型)为29.1%;rs1801133纯合突变(TT型)22.9%、杂合突变(CT型)48.5%;rs1801131、rs1801133双杂合突变为16.7%。结论:备孕二胎女性人群中存在一定的先心病环境危险因素暴露和MTHFR相关位点基因多态性。加强女性孕前保健,为高危人群制定个性化叶酸增补方案并降低先心病危险因素的暴露,从而做好出生缺陷一级预防,提高出生人口质量。