Jianmeng Liu

Folic Acid Supplementation During Early Pregnancy and the Risk of Gestational Hypertension and Preeclampsia

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 (&agr;=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 &mgr;g folic acid alone during early pregnancy cannot prevent the occurrence of gestational hypertension and preeclampsia.

Variable contribution of the MTHFR C677T polymorphism to non-syndromic cleft lip and palate risk in China

Non‐syndromic cleft lip with or without cleft palate (nsCL/P) is one of the most common craniofacial malformations among newborn infants. It has been demonstrated that periconceptional folic acid supplementation may reduce the occurrence of offspring with clefts, particularly in the North China; however, the mechanism remains unknown. Our study of a thermolabile polymorphism (C677T) of methylenetetrahydrofolate reductase (MTHFR) gene in 170 Chinese case‐parent triads revealed a moderate association between this MTHFR polymorphism and nsCL/P in a population from North China, but not in a population from South China. Moreover, the study revealed that the heterozygous parents in the North were about twice as likely to transmit the high‐risk T allele to affected cases, as that observed in the South (OR = 2.24, 95% CI: 1.08–4.65). Thus, the MTHFR polymorphism is a significant risk factor for nsCL/P in this Northern Chinese population. Our study suggested possible genetic heterogeneity in the development of nsCL/P among Northern and Southern populations in China.

Indoor Air Pollution From Coal Combustion and the Risk of Neural Tube Defects in a Rural Population in Shanxi Province, China

The authors evaluated indoor air pollution from coal combustion (IAPCC) as a potential risk factor for neural tube defects (NTDs) in a rural population in Shanxi Province, China. The studied rural population has both high IAPCC exposure and a high prevalence of NTDs. A population-based case-control study was used to identify 610 NTD cases and 837 normal controls between November 2002 and December 2007. Information was collected within 1 week following delivery or pregnancy termination due to prenatal NTD diagnosis. The authors derived an exposure index by integrating a series of IAPCC-related characteristics concerning dwelling and lifestyle. Compared with women with no IAPCC exposure, women with any exposure at all had a 60% increased risk of having a child with an NTD (adjusted odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.1, 2.1). An increased NTD risk was linked to both residential heating (adjusted OR = 1.7, 95% CI: 1.1, 2.4) and cooking (adjusted OR = 1.5, 95% CI: 1.1, 2.1). The risk increased with increases in the exposure index, showing a dose-response trend (P < 0.001). This is the first known study to link IAPCC to NTDs. Additional studies are needed to confirm the link between IAPCC and NTDs.

Placental concentrations of mercury, lead, cadmium, and arsenic and the risk of neural tube defects in a Chinese population.

To examine whether in utero exposure to mercury (Hg), cadmium (Cd), lead (Pb) and arsenic (As) is associated with an elevated neural tube defects (NTDs) risk, placental concentrations of total Hg, Cd, Pb and As were measured with an inductively coupled plasma mass spectrometer (ICP-MS) in 36 anencephaly and 44 spina bifida cases as well as in 50 healthy controls. The median Hg concentration in the NTD cases (2.25 ng/g) was higher than that of the controls (1.16 ng/g). The odds ratio (OR) for an Hg concentration above the median was 8.80 (95% CI 3.80-20.36) for the NTD cases. NTD risks increased for the second and third high levels of the concentrations, with ORs of 2.70 (95% CI 1.13-6.43) and 18.20 (95% CI 5.45-60.73), respectively. Therefore, higher placental levels of Hg are associated with an elevated risk of NTDs.

Urinary tract abnormalities in Chinese rural children who consumed melamine-contaminated dairy products: a population-based screening and follow-up study

Background: Kidney damage related to consumption of melamine-contaminated dairy products by young children in China has been described. However, no studies have reported on the population-based prevalence of kidney damage among exposed children or on the condition of affected children after follow-up. Methods: We conducted an ultrasound-based screening in September 2008 of 7933 children younger than 36 months of age who lived in a rural area in China where the dairy products most highly contaminated with melamine were sold. We monitored children who had evidence of nephrolithiasis or hydronephrosis at screening using renal ultrasonography after one, three and six months. We also collected information from the mothers of affected children about consumption of melamine-contaminated products between June and August 2008. Results: The overall prevalence of urinary tract abnormalities among screened children was 0.61% (95% confidence interval [CI] 0.45%–0.80%). The mean exposure dose of melamine was estimated to be 116 (range 36–220) mg per day. Of the 48 affected children, 43 (89.6%) were asymptomatic, 2 had symptoms and were hospitalized, and 3 had symptoms but treatment had been not sought for them. Of the 46 children for whom six-month follow-up information was available, renal abnormalities persisted in 5 children and resolved in the remaining 41. Interpretation: Among children who underwent screening, 0.61% showed ultrasonographic evidence of nephrolithiasis or hydronephrosis. Most of the affected children were asymptomatic. The majority of the affected children recovered from the toxic effects of melamine over time without specific treatment. Renal abnormalities remained in 12% of the affected children.

Micronutrient supplementation and pregnancy outcomes: double-blind randomized controlled trial in China.

BACKGROUND Beyond perinatal folic acid supplementation, the need for additional prenatal prophylaxis of iron with or without other micronutrients remains unclear. We aim to investigate the maternal and infant health effects of iron plus folic acid and multiple micronutrient supplements vs folic acid alone when provided to pregnant women with no or mild anemia. METHODS In this randomized double-blind controlled trial, 18,775 nulliparous pregnant women with mild or no anemia were enrolled from 5 counties of northern China from May 2006 through April 2009. Women were randomly assigned to daily folic acid (400 μg) (control), folic acid-iron (30 mg), or folic acid, iron, and 13 additional vitamins and minerals provided before 20 weeks gestation to delivery. Primary outcome was perinatal mortality. Secondary outcomes included neonatal and infant mortality, preterm delivery, birth weight, birth length, gestational duration, and maternal hemoglobin concentration and anemia. RESULTS A total of 92.7% of women consumed 80% to 100% of supplements as instructed. On average, women consumed 177 supplements. Compared with daily prenatal folic acid, supplementation with iron-folic acid with or without other micronutrients did not affect the rate of perinatal mortality (8.8, 8.7, and 8.3, respectively) per 1000 births, and relative risks (RRs) were 1.00 (95% CI, 0.68-1.46; P = .99) and 0.94 (95% CI, 0.64-1.39; P = .76), respectively. Risk of other adverse maternal and infant outcomes also did not differ, except that RRs for third-trimester maternal anemia were 0.72 (95% CI, 0.63-0.83; P < .001) and 0.71 (95% CI, 0.62-0.82; P < .001), respectively. CONCLUSION Prenatal iron-folic acid and other micronutrient supplements provided to Chinese women with no or mild anemia prevented later pregnancy anemia beyond any benefit conferred by folic acid alone but did not affect perinatal mortality or other infant outcomes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00133744.

Time to consider the risks of caesarean delivery for long term child health

Jan Blustein and Jianmeng Liu examine the evidence linking caesarean delivery with childhood chronic disease and say that guidelines on delivery should be reviewed with these risks in mind

Association of reduced folate carrier gene polymorphism and maternal folic acid use with neural tube defects

This study was designed to investigate whether the risk for neural tube defects (NTDs) was associated with reduced folate carrier gene (RFC1 A80G) polymorphism and/or with the interaction between the RFC1 gene and maternal periconceptional use of folic acid. One hundred four nuclear families with NTDs and 100 non‐malformed control families were sampled to investigate the potential interaction between maternal or the offsprings RFC1 (A80G) genotypes and the maternal periconceptional use of folic acid through a population‐based case–control study. RFC1 (A80G) genotypes were detected using PCR‐restricted fragment length polymorphism (PCR‐RFLP). Mother who had the GG genotype and did not take folic acid had an elevated risk for NTDs (OR = 5.43, 95% CI = 1.68–18.28) as compared to the mother who had AA or GA genotype and took maternal periconceptional folic acid. The interactive coefficient was 1.12 between maternal GG genotype and the periconceptional folic acid non‐use. The risk for having an infant with NTDs was 8.80 (95% CI = 2.83–28.69) for offspring with the GG genotype, as compared to the offspring with AA or GA genotype among the mothers who did not take folic acid supplements. The interactive coefficient was 1.45 for offspring with the GG genotype and without maternal periconceptional supplementation of folic acid. Our findings suggest that there is a potential gene–environment interaction on the risk of NTDs between maternal or offspring RFC1 GG genotype and maternal periconceptional intake of folic acid. The RFC1 is likely to be an important candidate gene in folate transportation and RFC1 GG genotype (A80G) may be associated with an increased risk for NTDs in this Chinese population.

Maternal passive smoking and risk of cleft lip with or without cleft palate.

Background: Maternal smoking has been consistently associated with increased risk of cleft lip with or without cleft palate (CL/P). Few studies have explored the possible effect of passive smoking. We examined the association between maternal passive smoking and the risk of CL/P among nonsmoking women in China. Methods: Subjects included 88 infants with CL/P and 651 infants with no major external birth defects. Data were collected by trained health workers through face-to-face interviews. Results: The odds ratio (OR) for CL/P associated with maternal passive smoking was 1.8 (95% confidence interval = 1.1–2.8). After adjustment for maternal occupation, periconceptional flu or fever, and infant sex, the risk was 2.0 (1.2–3.4). The adjusted ORs for exposure levels of 1–6 times per week and more than 6 times per week (at least 1 cigarette each time) were 1.6 (0.9–2.9) and 2.8 (1.5–5.2), respectively. Conclusion: Maternal passive smoking during pregnancy was associated with an increased risk for CL/P in offspring.

Periconceptional use of folic acid in Shanxi Province of northern China

OBJECTIVE To understand the periconceptional use of folic acid and its association with selected characteristics in northern China. DESIGN As part of a population-based case-control study on external structural birth defects, we analysed periconceptional use of folic acid among control mothers. SETTING The study was conducted in four counties (Pingding, Xiyang, Taigu and Zezhou) in Shanxi Province of northern China. SUBJECTS The subjects in this study were the control mothers, who were interviewed between January 2003 and May 2005. RESULTS Of the 480 respondent mothers, 49 women (10.2%) reported ever using folic acid supplements, and only 16 women (3.3%) used it periconceptionally. The rates of any use and periconceptional use did not change significantly with study year. Periconceptional use of folic acid was significantly increased among women with more than high school education (odds ratio (OR) = 4.57, P < 0.10), women who were not farmers (OR = 4.72, P < 0.05), women with a history of birth-defect-affected pregnancy (OR = 32.73, P < 0.05) and women who planned their pregnancy (OR = 7.88, P < 0.10). CONCLUSION The rate of periconceptional folic acid use was among the lowest of those reported from other countries. More work should be done to improve preconceptional use of folic acid with special attention on less educated women and women farmers.