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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., (© The Author(s) 2019; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

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., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

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.

Concerns have been raised about the benefits of Fe-containing supplements on infant birth weight among women with normal/high Hb levels at baseline. Thus far, no clinical trials have examined whether the effects of prenatal Fe-containing supplements on birth weight vary by maternal Hb levels. We compared the effects of Fe-folic acid (IFA) or multiple micronutrients (MMN) with folic acid (FA) supplements on birth weight among pregnant women with mild/no anaemia or high Hb levels. A double-blind randomised controlled trial was conducted in 2006-2009. In total, 18 775 pregnant women with mild/no anaemia (145 g/l) baseline Hb levels, IFA and MMN supplements increased birth weight by 91·44 (95% CI 3·37, 179·51) g and 107·63 (95% CI 21·98, 193·28) g (P<0·05), respectively, compared with the FA group. No differences were found between the IFA and the MMN group, regardless of maternal Hb concentration. In conclusion, the effects of Fe-containing supplements on birth weight depended on baseline Hb concentrations. The Fe-containing supplements improved birth weight in women with very high Hb levels before 20 weeks of gestation.

Emerging evidence has suggested that folic acid-containing multivitamins may markedly reduce the risk of gestational hypertension or preeclampsia. We examined whether maternal supplementation with folic acid alone during early pregnancy can prevent the occurrence of gestational hypertension and preeclampsia. The data are from a large population-based cohort study established to evaluate the effectiveness of the campaign to prevent neural tube defects with folic acid supplementation in China. We selected participants who were registered in 2 southern provinces, had exact information on folic acid use, and were not affected by chronic hypertension or diabetes mellitus before 20 weeks gestation. A logistic regression model was used to adjust for the effects of the main potential confounders, including age, body mass index, education, occupation, parity, and multiple births. The study size had 99.9% power (α=0.05) to detect a decrease of 10% over the unexposed rate of 9.4% for gestational hypertension. Among the 193 554 women (47.9% took folic acid, 52.1% did not), the overall incidence of gestational hypertension and preeclampsia was 9.5% and 2.5%, respectively. The incidence of gestational hypertension and preeclampsia was 9.7% and 2.5% for women who took folic acid, and 9.4% and 2.4% for women who did not use it. The adjusted risk ratio associated with folic acid use was 1.08 (95% confidence interval, 1.04-1.11) for gestational hypertension and 1.11 (95% confidence interval, 1.04-1.18) for preeclampsia. Our findings suggest that daily consumption of 400 μg folic acid alone during early pregnancy cannot prevent the occurrence of gestational hypertension and preeclampsia.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To provide updated information about demographic variations and temporal trends in the prenatal use of multiple micronutrient (MMN) supplements in the metropolitan areas of China.Design: Descriptive analysis of routine prenatal healthcare data between 2013 and 2017.Setting: Chaoyang District, Beijing, China.Participants: A total of 197 346 pregnant women who attended their first prenatal care visit and provided information about MMN supplementation during the periconceptional period.Results: Of these pregnant women, 60·6 % reported consuming prenatal MMN supplements. In multivariate-adjusted models, there were significant gradients of age, education and parity in prenatal MMN supplementation, with the highest likelihood of MMN use among the oldest, the most highly educated and nulliparous women (Pfor trend < 0·001). Compared with that among unemployed women, prenatal MMN supplementation was more common among the employed, especially those engaged in business (adjusted relative risks (95 % CI): 1·08 (1·06, 1·10)) and management (1·10 (1·08, 1·12)). The proportion of prenatal MMN supplementation was 57·0 % in 2013, which increased to 63·5 % in 2017 (Pfor trend < 0·001). The trends varied by age, education and parity (Pfor heterogeneity < 0·001), whereas no significant difference was observed in trends across subgroups of ethnicity or occupation. The greatest magnitude increase in MMN supplement use occurred in women of age < 25 years (annual percent change: 5·7 %), less than high school education (9·6 %), parity ≥ 2 (6·8 %) or unemployment (6·1 %).Conclusion: Approximately two-thirds of women consumed prenatal MMN supplements during the periconceptional period in the central area of Beijing and the proportion increased over time, indicating a need to evaluate the effectiveness and safety and to develop a guideline for relatively well-nourished women. [ABSTRACT FROM AUTHOR]

Both inadequate and excessive gestational weight gain (GWG) have been shown to increase the risk of adverse pregnancy outcomes, but the risk profiles of GWG rate are unclear. We aimed to examine the associations between GWG rate in the second/third trimester and a spectrum of pregnancy outcomes. This study consisted of 14 219 Chinese rural nulliparous women who participated in a randomised controlled trial of prenatal micronutrient supplementation during 2006–2009. The outcomes included stillbirth, neonatal and infant death, preterm birth, macrosomia, low birth weight (LBW) and large and small for gestational age (LGA and SGA, respectively). GWG rate was divided into quintiles within each BMI category. Compared with women in the middle quintile, those in the lowest quintile had higher risks of neonatal death (adjusted OR 2·27; 95 % CI 1·03, 5·02), infant death (adjusted OR 1·85; 95 % CI 1·02, 3·37) and early preterm birth (adjusted OR 2·33; 95 % CI 1·13, 4·77), while those in the highest quintile had higher risks of overall preterm birth (adjusted OR 1·28; 95 % CI 1·04, 1·59), late preterm birth (adjusted OR 1·25; 95 % CI 1·00, 1·56), LBW (adjusted OR 1·48; 95 % CI 1·02, 2·15), macrosomia (adjusted OR 1·89; 95 % CI 1·46, 2·45) and LGA (adjusted OR 1·56; 95 % CI 1·31, 1·85). In conclusion, very low and very high GWG rates in the second/third trimester appear to be associated with adverse pregnancy outcomes in Chinese nulliparous women, indicating that an appropriate GWG rate during pregnancy is necessary for neonatal health. [ABSTRACT FROM AUTHOR]

Purpose: We investigated whether daily supplementation with low-dose B vitamins in the healthy elderly population improves the Framingham risk score (FRS), a predictor of cardiovascular disease risk. Methods: Between 2007 and 2012, a double-blind randomized controlled trial was conducted in a rural area of North China. In all, 390 healthy participants aged 60-74 were randomly allocated to receive daily vitamin C (50 mg; control group) or vitamin C plus B vitamins (400 µg folic acid, 2 mg B, and 10 µg B; treatment group) for 12 months. FRSs were calculated for all 390 subjects. Results: Folate and vitamin B plasma concentrations in the treatment group increased by 253 and 80 %, respectively, after 6 months, stopped increasing with continued supplementation after 12 months and returned to baseline levels 6 months after supplementation cessation. Compared with the control group, there was no significant effect of B vitamin supplementation on FRSs after 6 months (mean difference −0.38; 95 % CI −1.06, 0.31; p = 0.279), whereas a significant effect of supplementation was evident after 12 months (reduced magnitude 7.6 %; −0.77; 95 % CI −1.47, −0.06; p = 0.033). However, this reduction disappeared 6 months after supplementation stopped (−0.07; 95 % CI −0.80, 0.66; p = 0.855). The reduction in FRS 12 months after supplementation was more pronounced in individuals with a folate deficiency (10.4 %; −1.30; 95 % CI −2.54, −0.07; p = 0.039) than in those without (4.1 %; −0.38; 95 % CI −1.12, 0.36; p = 0.313). B vitamins increased high-density lipoprotein cholesterol by 3.4 % after 6 months (0.04; 95 % CI −0.02, 0.10; p = 0.155) and by 9.2 % after 12 months (0.11; 95 % CI 0.04, 0.18; p = 0.003). Compared with the control group, this change in magnitude decreased to 3.3 % (0.04; 95 % CI −0.02, 0.10; p = 0.194) 6 months after supplementation cessation. Conclusions: Daily supplementation with a low-dose of B vitamins for 12 months reduced FRS, particularly in healthy elderly subjects with a folate deficiency. These reduced effects declined after supplementation cessation, indicating a need for persistent supplementation to maintain the associated benefits. [ABSTRACT FROM AUTHOR]