Aiguo Ren

Association of selected persistent organic pollutants in the placenta with the risk of neural tube defects

Persistent organic pollutants (POPs) have been associated with a wide range of adverse health effects. Our case–control study was performed to explore the association between placental levels of selected POPs and risks for neural tube defects (NTDs) in a Chinese population with a high prevalence of NTDs. Cases included 80 fetuses or newborns with NTDs, whereas the controls were 50 healthy, nonmalformed newborn infants. Placental concentrations of polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides, polychlorinated biphenyls, and polybrominated diphenyl ethers were analyzed by gas chromatography–mass spectrometry. The medians of PAHs, o,p′-isomers of dichlorodiphenyltrichloroethane (DDT) and metabolites, α- and γ-hexachlorocyclohexane (HCH), and α-endosulfan were significantly higher in case placentas than in controls. PAH concentrations above the median were associated with a 4.52-fold [95% confidence interval (CI), 2.10–9.74) increased risk for any NTDs, and 5.84- (95% CI, 2.28–14.96) and 3.71-fold (95% CI, 1.57–8.79) increased risks for anencephaly and spina bifida, respectively. A dose–response relationship was observed between PAH levels and the risk of NTDs, with odds ratios for the second, third, and fourth quartiles, compared with the first, of 1.77- (95% CI, 0.66–4.76), 3.83- (95% CI, 1.37–10.75), and 11.67-fold (95% CI, 3.28–41.49), respectively. A dose–response relationship was observed for anencephaly and spina bifida subtypes. Similar results were observed for o,p′-DDT and metabolites, α-HCH, γ-HCH, and α-endosulfan, whereas no dose–response relationship was observed for the last two pollutants. Elevated placental concentrations of PAHs, o,p′-DDT and metabolites, and α-HCH were associated with increased risks of NTDs in this population.

Low first-trimester hemoglobin and low birth weight, preterm birth and small for gestational age newborns

Objective: To examine the relationship between first‐trimester hemoglobin (Hb) concentration and risk of low birth weight (LBW), preterm birth and small for gestational age (SGA). Methods: Data were obtained from a population‐based prenatal care program in China. A total of 88,149 women who delivered during 1995–2000 and had their Hb measured in the first trimester were selected as study subjects. Results: The prevalence of anemia (Hb < 110 g/L) was 22.1% in the first trimester. The risk of LBW, preterm birth and SGA was increased steadily with the decrease of first‐trimester Hb concentration. After controlling for confounding factors, women with Hb 80–99 g/L had significantly higher risk for LBW (OR = 1.44, 95% CI 1.17–1.78), preterm birth (OR = 1.34, 95% CI 1.16–1.55) and SGA (OR = 1.13, 95% CI 0.98–1.31) than women with Hb 100–119 g/L. No elevated risk was noted for women with Hb ≥ 120 g/L. Conclusion: Low first‐trimester Hb concentration increases the risk of LBW, preterm birth and SGA.

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.

Comparison of blood folate levels among pregnant Chinese women in areas with high and low prevalence of neural tube defects.

OBJECTIVE To characterise plasma and red-blood-cell (RBC) folate status among pregnant women in an area with an extremely high prevalence of neural tube defects, and to compare them with those of women from a low prevalence area. DESIGN A cross-sectional survey conducted in 2003. SETTING One county and one city from each of the high prevalence area and the low prevalence area in China. SUBJECTS Five hundred and sixty-two women in their first trimester of pregnancy in the high prevalence area and 695 pregnant women in the low prevalence area. RESULTS Women in the high prevalence area had less than half the plasma and RBC folate concentrations (12.2 and 440.0 nmol l- 1, respectively) of women in the low prevalence area (33.5 and 910.4 nmol l- 1, respectively). In the high prevalence area, 40% of rural women were deficient in RBC folate and 50% were deficient in plasma folate; 20% of urban women were deficient in RBC folate and 30% deficient in plasma folate. In contrast, only 4% (RBC folate) and 6% (plasma folate) of rural women, and 2% (RBC folate) and 1% (plasma folate) of urban women, were folate-deficient in the low prevalence area. Less than 10% of rural and about 26% of urban women in the high prevalence area took folic acid periconceptionally, compared with 70% and 60% of women in the low prevalence area. CONCLUSIONS Blood folate deficiency is highly prevalent among pregnant women in an area of China with a very high prevalence of neural tube defects.

Caesarean delivery, caesarean delivery on maternal request and childhood overweight: a Chinese birth cohort study of 181 380 children.

What is already known about this subject Both rates of caesarean section and childhood overweight have been steadily increasing over the past decade in many parts of the world. Caesarean delivery on maternal request contributes remarkably to the rising trend of caesarean births. A few small‐scale studies suggest that caesarean section may be associated with later overweight and obesity, whereas little is known about the impact of caesarean delivery on maternal request.

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.