Association of age at menarche with gestational hypertension and preeclampsia: A large prospective cohort in China.

This study explored the potential association between age at menarche and the risks of gestational hypertension and preeclampsia in Chinese women. Data were sourced from the China-US Collaborative Project for Neural Tube Defects Prevention, a large population-based cohort study. Our study consisted of 209 411 women pre-registered for pregnancy in two provinces in South China. Trained healthcare workers measured blood pressure at registration and recorded other pertinent health information. Using logistic regression, we assessed the correlations between age at menarche and the likelihood of developing gestational hypertension and preeclampsia, considering confounders such as maternal age, body mass index, ethnicity, parity, folic acid supplementation, education level, and occupation. The observed incidences for gestational hypertension and preeclampsia were 9.65% and 2.54%, respectively. The adjusted odds ratios (ORs) for gestational hypertension, based on age at menarche, were as follows: ≤13 years, 1.18 (95% confidence interval: 1.11-1.26); 14 years, 1.09 (1.04-1.15); 15 years, 1.11 (1.06-1.16); 16 years, 1.06 (1.01-1.12); and ≥17 years, 1.00 (reference; P for trend < .001). The correlation between age at menarche and preeclampsia varied across age groups, with the following respective ORs: 1.35 (1.20-1.52), 1.21 (1.09-1.34), 1.27 (1.15-1.39), 1.14 (1.03-1.26), and 1.00 (reference; P for trend < .001). This association appeared to be more pronounced in women with no folic acid supplementation and those with a lower education level. In conclusion, an earlier age at menarche seems to be linked to increased risks of gestational hypertension and preeclampsia.

Folic acid supplements and perinatal mortality in China.

Introduction: Periconceptional use of multivitamins containing folic acid prevents external major birth defects, especially neural tube defects. We aimed to explore the effects of maternal folic acid supplementation alone on perinatal mortality with or without external major birth defects plus neural tube defects. Methods: From the China-US Collaborative Project for Neural Tube Defects Prevention, we identified 222, 303 singleton pregnancies with detailed information on periconceptional folic acid use, defined as folic acid supplementary before the last menstrual date until to the end of the first trimester. Perinatal mortality included stillbirths after 20 weeks' gestation and early neonatal deaths within 7 days of delivery. Results: Among the fetuses or infants of women who did not take folic acid, the rate of perinatal mortality was 2.99% and 1.62% at least 20 weeks' gestation in the northern and southern regions. Among the fetuses or infants of the women with periconceptional use of folic acid, the rates were 1.85% and 1.39% in the northern and southern region. The estimated relative risk for perinatal mortality [adjusted risk ratio (RR), 0.72; 95% confidence interval (CI), 0.61- 0.85], stillbirth (adjusted RR, 0.78; 95% CI, 0.64-0.96), early neonatal mortality (adjusted RR, 0.61; 95% CI, 0.45-0.82), and neonatal death (adjusted RR, 0.64; 95% CI, 0.49-0.83) in northern China was significantly decreased in association with periconceptional folic acid supplementation. Compared with northern, there was a lesser effect in southern China. Conclusion: Periconceptional intake of 400µg folic acid daily reduces the overall risk perinatal mortality, as well as the risk from external major birth defects and neural tube defects, especially in northern China.

Cesarean delivery on maternal request and common child health outcomes: A prospective cohort study in China.

Background: Cesarean delivery vs vaginal delivery was reported to increase the risks of childhood obesity, pneumonia, anemia, and neurobehavioral disorders, but few studies were able to deal with the confounding biases associated with medical conditions indicating cesareans. This prospective cohort study aims to investigate the associations of non-medically indicated cesarean delivery on maternal request (CDMR) with these child health outcomes. Methods: Among 17 748 liveborn infants whose mothers (primiparas) participated in a randomized controlled trial on micronutrient supplementation and pregnancy outcomes during 2006-2009 in 5 rural counties in Hebei Province, China, 6972 singletons born by full-term spontaneous vaginal delivery (SVD) and 3626 by CDMR were extracted for the assessments of obesity (weight-for-height z-score >3) and pneumonia (self-reported) at 1.5-5 years in 2011. Some children were further randomly selected from these two groups for the assessments of anemia (hemoglobin <110 g/L, 2341 SVD and 2417 CDMR) and neurobehavioral disorders (raw score of Child Behavior Checklist larger than the 90th percentile of the normative sample, 1257 SVD and 1060 CDMR). Results: Compared with SVD, CDMR was associated with increased risks of obesity (adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) = 1.14-1.75, P = 0.002) and anemia (aOR = 1.65, 95% CI = 1.28-2.12, P < 0.001), but not with the risk of pneumonia (aOR = 1.16, 95% CI = 0.94-1.45, P = 0.17) or neurobehavioral disorders (aORs varied from 0.82 to 0.91, P > 0.05) in childhood. Conclusions: Cesarean delivery, independent of cesarean indications, is likely associated with childhood obesity and anemia, indicating a need to keep pregnant women informed, especially those seeking CDMR, a need to explore possible improvement on obstetric service, and even a need for main stakeholders to reach a compromise in making a cesarean decision. Trial registration: ClinicalTrials.gov: NCT00133744 and NCT01404416.

Effects of prenatal micronutrients supplementation timing on pregnancy-induced hypertension: Secondary analysis of a double-blind randomized controlled trial.

In this secondary analysis of data from a double-blind randomized controlled trial (clinicaltrials.gov identifier: NCT00133744) of micronutrient supplementation (multiple micronutrients [MMN], iron-folic acid [IFA] and folic acid [FA] alone), we examined the potential modifying effect of gestational age at enrolment on the association of antenatal supplementation and pregnancy-induced hypertension (PIH). We included 18,775 nulliparous pregnant women with mild or no anaemia who were enrolled at 20 weeks of gestation or earlier from five counties of northern China. Women were randomly assigned to receive daily FA, IFA or MMN from enrolment until delivery. We used logistic regression to evaluate the association between PIH and timing of micronutrient supplementation. The incidence of PIH was statistically significantly lower among women who began MMN supplementation before 12 gestational weeks compared with women who began MMN supplementation at 12 weeks or later (RR = 0.74, 95% CI: 0.60-0.91). A similar protective effect was observed for both early-onset (<28 weeks, RR 0.45, 0.21-0.96) and late-onset of PIH (≥28 weeks, RR 0.77, 0.63-0.96). No statistically significant association was observed between PIH occurrence and timing of supplementation for FA or IFA. Maternal MMN supplementation and antenatal enrolment during the first trimester of pregnancy appeared to be of importance in preventing both early- and late-onset of PIH.

Folic acid supplementation and risk for fetal abdominal wall defects in China: results from a large population-based intervention cohort study.

Folic acid (FA) can reduce the risk for selected birth defects other than neural tube defects. We examined whether FA has preventive effects against fetal abdominal wall defects (AWD) in a unique intervention cohort in China. Birth outcomes of 247 831 singleton births from a population-based cohort study with detailed pre-conceptional FA intake information were collected in China in 1993-1996. Information on births at 20 complete gestational weeks, including live births, stillbirths and pregnancy terminations, and all structural birth defects regardless of gestational week were recorded. The birth prevalence of omphalocele, gastroschisis and total fetal AWD was classified by maternal FA supplementation. The prevalence of total AWD was 4·30 per 10 000 births among women who took FA compared with 13·46 per 10 000 births among those who did not take FA in northern China and 6·28 and 5·18 per 10 000 births, respectively, in southern China. The prevalence of omphalocele was 0·54 per 10 000 births among women who took FA compared with 3·74 per 10 000 births among those who did not take FA in northern China and 1·79 and 1·44 per 10 000 births, respectively, in southern China. FA supplementation significantly prevented total AWD in multivariate analysis (relative risk 0·26, 95 % CI 0·11, 0·61) in northern China, although no preventive effect of FA on AWD was observed in southern China. FA supplementation successfully reduced the prevalence of AWD in northern China.

Folic acid supplementation and risk for congenital hydrocephalus in China.

OBJECTIVE: We examined whether folic acid (FA) supplementation prevented congenital hydrocephalus (CH) in more than 200 000 births in China. DESIGN: A large population-based cohort study. SETTING: All births at 20 complete gestational weeks, including live births, stillbirths and pregnancy terminations, and all structural birth defects regardless of gestational week were recorded. The prevalence of births with CH was classified by maternal characteristics and FA supplementation. CH was diagnosed in accordance with code 742.3 of the International Classification of Diseases, Ninth Revision, Clinical Modification, while non-neural tube defect (NTD) CH refers to CH without anencephaly (740), spina bifida (741) or encephalocele (742·0). PARTICIPANTS: A total of 247 831 pregnant women who delivered with known outcomes were included. RESULTS: A total of 206 cases of CH (0·83 per 1000 births) and 170 cases of non-NTD CH (0·69 per 1000 births) were recorded in the study. The prevalence of CH and non-NTD CH was higher in women in the no supplementation group than those in the FA supplementation group (0·92 and 0·72 v. 0·75 and 0·65 per 1000 births, respectively). FA supplementation during the periconceptional period significantly prevented CH (OR = 0·29, 95 % CI 0·12, 0·69) and non-NTD CH (OR = 0·34, 95 % CI 0·12, 0·97) in northern China, especially in a high-compliance group (≥ 80 %). CONCLUSIONS: Periconceptional FA supplementation did not significantly prevent CH overall in the current study. However, in the north of China with common maternal folate insufficiency, there was some evidence.

Maternal periconceptional body mass index and risk for neural tube defects: results from a large cohort study in China.

Background: Case-control studies have consistently suggested an association between pre- or periconceptional maternal obesity and an increased risk for neural tube defects (NTDs). Few studies have examined the association between body mass index (BMI) and NTDs using measured weight and height. We examined this association in a large cohort study in China.Methods: We used data from a large population-based cohort study established to evaluate the effectiveness of folic acid supplementation to prevent NTDs in China. BMI was computed using maternal weight and height measured before pregnancy or during early pregnancy. External birth defects were identified through a unique birth defects surveillance system. We estimated the birth prevalence and prevalence odds ratios (POR) for NTDs by Chinese BMI categories, controlling for potential confounders.Results: Our study population included a total of 194,844 women. We observed significantly elevated risk for spina bifida (adjusted POR = 5.4, 95% CI: 1.3-22.5) among children born to obese compared to normal weight women. Among women who took folic acid supplements, the adjusted POR for spina bifida among obese women was 10.0 (95% CI: 2.3-42.6) compared to pill users who were of normal weight. Borderline significantly elevated risk was observed for anencephaly (adjusted POR = 1.8; 95% CI: 1.0-3.2) among children born to underweight compared to normal weight women.Conclusions: Our findings suggest that maternal periconceptional obesity may be associated with an increased risk for spina bifida. Maternal underweight may be associated with increased risk for anencephaly.

Association between tea drinking and plasma folate concentration among women aged 18-30 years in China.

OBJECTIVE: Association was found between tea and neural tube defects. However, few studies investigated the relationship between tea consumption and blood folate levels. We aimed to investigate the association between tea consumption and plasma folate concentrations among women aged 18-30 years in different ethnicities of China. DESIGN: Data were obtained from a national cross-sectional study conducted from 2005 to 2006 of women aged 18-30 years in China. Socio-demographic characteristics and lifestyle were obtained from a questionnaire. Dietary folate intake was determined by 24-h dietary recall. Plasma folate concentrations were measured by a microbiological assay. Multiple linear regression model was used to calculate partial regression coefficients after adjusting for confounding factors. SETTING: Nine provinces or autonomous regions in China. PARTICIPANTS: A total of 2932 women aged 18-30 years in China. RESULTS: After stratifying by ethnicity and tea type, tea consumption was significantly positively associated with plasma folate levels in Han women who drank unfermented tea weekly (ß = 0·067, and P = 0·037) or daily (ß = 0·119, and P = 0·031) and in Uighur women who drank fermented tea weekly (ß = 0·325, and P = 0·028). For women who drank unfermented tea in Han ethnicity, weekly and daily tea drinkers had 6·77 % (95 % CI: 6·36 %, 7·21 %) and 7·13 % (95 % CI: 6·40 %, 7·96 %) increase in plasma folate concentration compared with no tea drinkers. CONCLUSIONS: There is a suggestion of possible positive association between unfermented tea drinking in Han ethnicity and plasma folate concentrations, for Chinese women aged 18-30 years. The relationship between tea drinking in other ethnic groups and plasma folate still needs to be further explored.

Periconceptional folic acid supplementation and risk of parent-reported asthma in children at 4-6†years of age.

BACKGROUND: Folic acid supplementation is universally recommended for women of child-bearing age to prevent fetal neural tube defects (NTDs). Concerns have arisen over the potential risk for childhood allergy and asthma due to folic acid supplementation. We examined whether periconceptional supplementation with low-dose folic acid only was associated with an increased risk for allergy symptoms or asthma in offspring at 4-6 years of age. METHODS: Out of 247 831 participating women enrolled in 1993-1996, 9090 were randomly selected and their children were followed up in 2000-2001. Information on mothers' demographic characteristics, folic acid supplementation and allergic diseases among children was collected. We used logistic regression to evaluate the association between folic acid intake and risk for allergic disease while adjusting for potential confounding factors. RESULTS: The rate of allergy symptoms was 1.54% among children whose mothers had taken folic acid compared with 2.04% among those whose mothers had not taken folic acid, and the rate of asthma was 0.92% and 0.88%, respectively. Maternal folic acid supplementation was not associated with risk for allergy symptoms or asthma, with odds ratios (95% CI) of 0.80 (0.58-1.11) and 1.04 (0.67-1.61), respectively. No differences in the occurrence of allergy symptoms or asthma were observed when data were analysed by timing of supplementation or compliance with folic acid supplementation. CONCLUSIONS: Supplementation with low-dose folic acid only during the periconceptional period did not increase risk for allergy symptoms or asthma in children at 4-6 years of age in a population without staple fortification with folic acid.

Folic acid supplementation and risk for congenital limb reduction defects in China.

BACKGROUND: Folic acid (FA) supplementation prevents neural tube defects, but there are mixed results for its ability to prevent limb reduction defects. We examined whether a preventive effect of FA supplementation exists for congenital limb reduction defects in a large population in China. METHODS: Data from a large population-based cohort study in China were used to evaluate the effects of FA supplementation on birth defects. All births at 20 complete gestational weeks, including live births, stillbirths and pregnancy terminations, and all structural congenital anomalies, regardless of gestational week, were recorded. A total of 247 831 singleton live births delivered at gestational ages of 20-42 weeks to women from northern and southern China with full information on FA intake were included. Limb reduction defects were classified by subtype and maternal FA supplementation. RESULTS: The prevalence of limb reduction defects was 2.7 per 10 000 births among women who took FA compared with 9.7 per 10 000 births among those who did not take FA in northern China; the prevalence was 4.5 and 3.8 per 10 000 births, respectively, in southern China. In both unadjusted and adjusted analyses, the estimated relative risk for upper limb reduction defects [odds ratio (OR) = 0.17, 95% confidence interval (CI): 0.04, 0.63] and total limb reduction defects (OR = 0.24, 95% CI: 0.08, 0.70) in northern China, but not for lower limb reduction defects ,was significantly decreased in association with FA supplementation in northern China. There was no association between FA supplementation and either an increased or decreased risk for limb reduction defects in southern China. CONCLUSIONS: FA supplementation successfully reduces the prevalence of limb reduction defects in northern China, whose population has low folate concentrations.

Micronutrient supplementation during pregnancy and the risk of pregnancy-induced hypertension: A randomized clinical trial.

BACKGROUND & AIMS: Increasing evidence suggests that iron-containing multiple micronutrient may reduce the risk of pregnancy-induced hypertension including gestational hypertension or preeclampsia. We aimed to examine whether 30 mg iron plus folic acid or multiple micronutrients during pregnancy reduces the risk of pregnancy-induced hypertension. METHODS: We conducted a secondary data analysis by the dataset from a double-blind randomized controlled trial in China from 2006 to 2009 that was conducted to investigate the effects of multiple micronutrient supplements on adverse pregnancy outcomes when provided to pregnant women with no/mild anemia. We used logistic regression to estimate the adjusted odds ratio and 95% confidence interval and test for effect modification. RESULTS: The incidence of pregnancy-induced hypertension was 7.1% (423/5923), 6.3% (374/5933) and 6.3% (372/5914) among the pregnant women who took folic acid only, iron-folic acid and multiple micronutrient supplements, respectively. The adjusted odds ratios associated with iron-folic acid supplements and multiple micronutrient supplements for pregnancy-induced hypertension were both nearly 0.88 (95% confidence interval, 0.76-1.02), compared with folic acid supplements only. Among pregnant women aged 20-24 years, iron-folic acid (adjusted odds ratios: 0.81, 95% confidence interval: 0.67-0.96) or multiple micronutrient supplementation (adjusted odds ratios: 0.83, 95% confidence interval: 0.70-0.99) can significantly reduce the risk of pregnancy-induced hypertension compared to folic acid supplementation. CONCLUSIONS: Overall, there were no significant differences in pregnancy-induced hypertension across supplement groups. However, among pregnant women aged 20-24 years, iron-containing multiple micronutrient supplementation was associated with a reduced risk of pregnancy-induced hypertension compared with folic acid supplements only. TRIAL REGISTRATION: ClinicalTrials.gov NCT00133744.

Periconceptional folic acid supplementation and sex difference in prevention of neural tube defects and their subtypes in China: results from a large prospective cohort study.

BACKGROUND: Folic acid (FA) supplementation is known to prevent neural tube defects (NTDs). We examined whether this preventive effect differs by the sex of the infant. METHODS: Data were gathered from a large population-based cohort study in China that evaluated the effects of FA supplementation on NTDs. All births at 20 complete gestational weeks, including live births, stillbirths, and pregnancy terminations, and all NTDs, regardless of gestational age, were recorded. In a northern China province, a total of 30,801 singleton live births to women whose use of FA supplements during the first trimester was known at the time were included in the study. The birth prevalence of NTDs was classified by sex, subtype, and maternal FA supplementation. Male to female rate ratios [RR] and their 95% confidence intervals [CI] were calculated. RESULTS: A total of 106 NTDs cases were recorded. The overall prevalence of NTDs was 2.5‰ among males and 4.4‰ among females; NTDs were less prevalent among males than among females (RR, 0.58; 95% CI, 0.54-0.63). There was a higher prevalence of anencephaly (RR, 0.34; 95% CI, 0.27-0.43) and spina bifida (RR, 0.73; 95% CI, 0.63-0.84) among females. However, FA supplementation led to significantly greater decreases in the rates of anencephaly (4.8‰) and total NTDs (7.6‰) in females than in males (1.6‰ and 2.8‰, respectively). CONCLUSIONS: FA supplementation successfully reduces the prevalence of NTDs in both male and female infants, although we found a significantly greater decrease in anencephaly and total NTDs in females than in males. How the protective effects of FA supplementation affect the sexes differently needs to be studied further.

Maternal haemoglobin concentration and risk of preterm birth in a Chinese population.

The aim was to examine the relationship between maternal haemoglobin (Hb) concentrations and risk of preterm birth by secondary analysis of data from a randomised controlled trial. This analysis included 10,430 women who were at least 20 years old and no more than 20 weeks of gestation. Results revealed neither first- nor second-trimester Hb concentrations were associated with the risk of preterm births. However, the risk of preterm birth increased when the Hb level was low (<130 g/L) in the first but high (≥130 g/L) in the second trimester, regardless of supplement type (iron-containing: AOR: 2.26, 95% CI: 1.37-3.73; non-iron-containing: AOR: 2.16, 95% CI: 1.11-4.21). In conclusion, maternal Hb concentrations were not associated with the risk of preterm birth. A low-Hb level in the first trimester but coupled with a high Hb level in the second was associated with an elevated risk of preterm birth. Impact statement What is already known on this subject: The relationship between maternal Hb concentration and preterm birth remains inconclusive. Some studies have shown an association between a low- or a high-Hb level and an increased risk of preterm birth. Others have not found such an association. Yet others have shown a U-shaped relationship. What do the results of this study add: Overall, maternal Hb concentrations in first or second trimester were not statistically associated with the risk of preterm birth. However, women with a low Hb concentration in the first trimester together with a high Hb concentration in the second trimester had an increased risk of preterm birth, compared to women who had a higher Hb concentration in the first trimester that remained similar during the second trimester. What are the implications are of these findings for clinical practice and/or further research: Our finding helps identify mothers who are at risk of having a preterm delivery. Investigating the underlying clinical causes of the unfavourable change in Hb levels and close follow-up to these women may help improve birth outcomes.

Impact of Periconceptional Folic Acid Supplementation on Low Birth Weight and Small-for-Gestational-Age Infants in China: A Large Prospective Cohort Study.

OBJECTIVES: To explore the effects of maternal folic acid supplementation alone during pregnancy on the incidence of low birth weight (LBW) and small-for-gestational-age (SGA) infant status. STUDY DESIGN: Data were derived from a large population-based cohort study performed in China to evaluate the prevention of neural tube defects with folic acid supplementation. The sample comprised 200 589 singleton live births registered in 2 southern Chinese provinces by mothers for whom detailed information on folic acid use was available. Gestational age was calculated from the first day of the last menstrual period. LBW was defined as a birth weight <2500 g. Infants were considered SGA when the age-adjusted birth weight was below the 10th percentile as defined by a national survey performed in 1998. Logistic regression was used to estimate the effects of folic acid after adjusting for the principal potential confounders. RESULTS: The overall incidence of LBW and SGA status was 2.18% and 5.82%, respectively. The incidence of LBW and SGA status was 2.09% and 5.73% in women who took folic acid, and 2.27% and 5.90% in those who did not. The adjusted risk ratios associated with folic acid use were 0.85 (95% CI: 0.80-0.90) for LBW and 0.93 (95% CI: 0.89-0.96) for SGA status. Folic acid use during pregnancy appeared to be particularly important to prevent LBW and SGA status. CONCLUSIONS: A maternal daily intake of 400 µg folic acid alone significantly reduced the risks of infant LBW and SGA status.

Effects of Prenatal Micronutrient Supplementation on Spontaneous Preterm Birth: A Double-Blind Randomized Controlled Trial in China.

In this secondary analysis of data from a double-blind randomized controlled trial carried out in northern China, we aimed to assess the effect of prenatal supplementation with multiple micronutrients (MMN) or iron + folic acid (IFA), versus folic acid (FA) alone, on risk of spontaneous preterm birth (SPB) and the impact of supplementation timing on SPB. A total of 18,775 nulliparous pregnant women enrolled between 2006 and 2009 were randomly assigned to receive daily FA, IFA, or MMN from the period before 20 weeks' gestation to delivery. The incidences of SPB for women consuming FA, IFA, and MMN were 5.7%, 5.6% and 5.1%, respectively. Compared with women given FA, the relative risks of SPB for those using MMN and IFA were 0.99 (95% confidence interval: 0.85, 1.16) and 0.89 (95% confidence interval: 0.79, 1.05), respectively. SPB incidence in women who started consuming FA, IFA, and MMN before the 12th week of gestation (4.6%, 4.2%, and 3.9%, respectively) was significantly reduced compared with starting supplement use on or after the 12th gestational week (6.9%, 7.2%, and 6.4%, respectively). Starting use of FA, IFA, or MMN supplements before the 12th week of gestation produced a 41%-45% reduction in risk of SPB. Early prenatal enrollment and micronutrient use during the first trimester of pregnancy appeared to be of particular importance for prevention of SPB, regardless of supplement group.

Levels of folate receptor autoantibodies in maternal and cord blood and risk of neural tube defects in a Chinese population.

BACKGROUND: After years of periconceptional folic acid supplementation, the prevalence of neural tube defects (NTDs) remains stable following the remarkable reduction observed immediately after the fortification practice. There is accumulating evidence that folate receptor (FR) autoimmunity may play a role in the etiology of folate-sensitive NTDs. METHODS: From 2011 to 2013, 118 NTD cases and 242 healthy controls were recruited from a population-based birth defects surveillance system in Northern China. Enzyme-linked immunosorbent assay was used to measure FR autoantibodies in maternal and cord blood. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Plasma FR autoantibodies levels were significantly elevated in mothers of infants with NTDs compared with mothers of healthy controls. Using the lowest tertile as the referent group, 2.20-fold (95% CI, 0.71-6.80) and 5.53-fold increased odds (95% CI, 1.90-16.08) of NTDs were observed for the second and third tertile of immunoglobulin G (IgG), respectively, and the odds of NTDs for each successive tertile of IgM was 0.98 (95% CI, 0.35-2.75) and 3.49 (95% CI, 1.45-8.39), respectively. A dose-response relationship was found between FR autoantibodies levels and risk of NTDs (P < 0.001 for IgG, P = 0.002 for IgM). The same pattern was observed in both subtypes of spina bifida and anencephaly. No significant difference in levels of cord blood FR autoantibodies was observed. CONCLUSION: Higher levels of FR autoimmunity in maternal plasma are associated with elevated risk of NTDs in a dose-response manner. Birth Defects Research (Part A) 106:685-695, 2016. © 2016 Wiley Periodicals, Inc.

Prevalence and trend of neural tube defects in five counties in Shanxi province of Northern China, 2000 to 2014.

BACKGROUND: The prevalence of neural tube defects (NTDs) in northern China is among the highest in the world. A massive folic acid supplementation program as a specific countermeasure was introduced in 2009. Examining trends in NTD prevalence may provide evidence for future intervention. METHODS: Data for 2000 to 2014 in five counties in northern China were obtained through a population-based birth defects surveillance system. All live births, stillbirths of over 20 gestational weeks, and pregnancy terminations because of NTDs at any gestational age were recorded. The prevalence of NTDs by gestational weeks (< 28 vs. ≥ 28), by calendar year, and by subtype was presented. RESULTS: From 2000 to 2014, a total of 234,225 births and 2027 cases of NTDs were recorded. The prevalence of total NTDs was extremely high during 2000 to 2004, but it began to decrease continuously thereafter, from a peak of 120.0/10,000 in 2004 to a low of 31.5/10,000 in 2014. A significant decrease (60%) was observed from 78.8/10,000 in 2009 to 31.5/10,000 in 2014, 5 years after the folic acid supplementation program was introduced. All three major subtypes, namely anencephaly, spina bifida, and encephalocele, showed a decline over this period. Although the perinatal (≥ 28 gestational weeks) prevalence of NTDs decreased progressively, the pre-perinatal (< 28 gestational weeks) prevalence of NTDs remained high until 2011 and then decreased. CONCLUSION: The prevalence of NTDs remains high despite a substantial and continuous decrease over the past 15 years. To further reduce NTD risk in the population, fortification staples with folic acid should be considered.

Tea consumption is not associated with reduced plasma folate concentration among Chinese pregnant women.

BACKGROUND: The aim of this study was to evaluate the relationship between tea consumption and plasma folate concentration in populations with high and low prevalence of neural tube defects (NTDs) in China. METHODS: Cross-sectional survey was conducted in three cities/counties in China, in which 1724 pregnant women during early second trimester were recruited and interviewed about tea consumption and folic acid use in 2011 to 2012. A total of 5-ml nonfasting blood sample was collected and plasma folate concentration was determined by microbiological assay. RESULTS: Approximately 16.2% of the women reported that they had ever drank tea during and before the current pregnancy, women with higher educational level, and those who resided in urban were more likely to drink tea. Most of them prefer green tea (55.2%); 13.6% of women drank tea ">6 times/week," and 29.0% of them drank "less than once a week." The median of plasma folate concentration was 48.7 nmol/L in women who drank tea while it is 45.2 nmol/L in women who did not drink tea, with no statistical difference. The results showed there was no association between tea drinking and plasma folate concentration in Chinese pregnant women stratified by folic acid supplementation and other selected characteristics. CONCLUSION: Low level of tea drinking is not associated with decreased plasma folate concentration in the Chinese populations with high and low prevalence of NTDs.

Effects of vitamin D supplementation during pregnancy on neonatal vitamin D and calcium concentrations: a systematic review and meta-analysis.

We conducted a meta-analysis to review the effects of vitamin D supplementation during pregnancy on neonatal 25-hydroxyvitamin D (25(OH)D) and calcium concentrations. Randomized controlled trials that supplemented subjects with vitamin D2 or D3 during pregnancy and reported cord blood 25(OH)D or calcium concentrations were included. A random-effect model was used to pool the data. Subgroup analyses were performed to explore the sources of heterogeneity. We searched PubMed, Web of Science, and Cochrane Library for relevant publications. Among 1768 publications identified by our search strategy, 13 studies met our inclusion criteria. Cord blood 25(OH)D concentration was significantly increased by maternal vitamin D supplementation (mean difference, 22.48 nmol/L; 95% confidence interval, 15.90-29.06 nmol/L) with high heterogeneity (I2 = 98.8%, P < .0001). No effects on cord blood calcium concentration was reported (mean difference, 0.05 mmol/L; 95% confidence interval, -0.04-0.13 mmol/L). Supplementation regimens and the different control groups may be the major sources of heterogeneity. Vitamin D supplementation during pregnancy can improve cord blood 25(OH)D concentration in women with low 25(OH)D concentration, but does not affect cord blood calcium concentration. Future researches are needed to evaluate the effect of maternal vitamin D supplementation in women with a normal 25(OH)D concentration and explore the combined effects of vitamin D, calcium, and multivitamins.

Plasma folate levels in early to mid pregnancy after a nation-wide folic acid supplementation program in areas with high and low prevalence of neural tube defects in China.

BACKGROUND: Folic acid supplementation is recommended for all women of child-bearing age to prevent neural tube defects (NTDs). A nation-wide folic acid supplementation program was implemented in rural areas of China since 2009; however, changes in plasma folate levels in pregnant women were unknown. METHODS: A cross-sectional survey was conducted in 2011 to 2012, with 1736 pregnant women enrolled, and results were compared with a previous survey in 2002 to 2004. A microbiological method was used to determine plasma folate levels. Preprogram and postprogram median plasma folate concentrations were compared while stratified by prevalence of NTDs and residence. RESULTS: In the high NTD prevalence population, plasma folate concentration increased to 33.4 (18.7, 58.4) nmol/L in the postprogram sample, which is 2.9 times of the preprogram. In the low NTD prevalence population, plasma folate increased to 67.9 (44.5, 101.9) nmol/L, which is 1.9 times of the preprogram. Gaps remained in plasma folate levels with respect to prevalence of NTDs and residence. Folic acid supplementation has a strong impact on plasma folate concentrations. Earlier supplementation (before the last menstrual period), increased supplementation frequency and more total days of supplementation were associated with a higher plasma folate concentration as demonstrated in both the high- and low-prevalence populations. CONCLUSION: Plasma folate levels among pregnant Chinese women increased dramatically after the nation-wide folic acid supplementation program in both rural and urban areas, and in populations of high and low NTD prevalence. The nation-wide program should have a component to ensure that supplementation begins before pregnancy.