Inadvertent antibiotic exposure during pregnancy may increase the risk for neural tube defects in offspring.

BACKGROUND: As emerging environmental contaminants, antibiotics pose potential threats to human health, in particular to pregnant women and infants. However, the potential harm of inadvertent antibiotic exposure (IAE) is often disregarded in light of the focus on intentional antibiotic use during pregnancy. Currently, little is known about the effects of IAE during pregnancy on fetal neural tube development. METHODS: In this case-control study, we used questionnaire data from 855 subjects to investigate the effects of intentional antibiotic use in early pregnancy on neural tube defects (NTDs). Then we tested for placental antibiotics in mothers who had not intentionally used antibiotics, and the compounds were detected in 379 subjects; these were considered IAE cases. We assessed the association between IAE during pregnancy and fetal NTDs using both multivariable logistic and multi-pollutant exposure models. We also analyzed the correlation between maternal dietary habits and placental antibiotics to explore possible sources of IAE. RESULTS: Only 50 of 855 participants (5.8%) intentionally used antibiotics and such use showed no significant association with NTD risk (odds ratio [OR] = 1.92, confidence interval [95%CI] = [0.66, 5.59]). However, 14 of 15 placental antibiotics were detected in 378 of 379 subjects (99.7%) and multivariable logistic analysis indicated that high levels of placental macrolides were significantly associated with increased NTD risk (4.42 [2.01-10.45]). Multi-pollutant exposure analysis suggested an increase in NTD risk with an increase in exposure to a mixture of placental antibiotics, among which macrolides were the most important contributor. In addition, the level of placental macrolides was positively correlated with the intake frequency of milk. Finally, mothers who drank river, well, or pond water had higher levels of placental macrolides than those who drank only tap water. CONCLUSIONS: Intentional antibiotic use during early pregnancy may not be associated with NTDs, while IAE during pregnancy is associated with higher NTD risk in offspring. Macrolides are crucial risk factors. Milk, and river, well, or pond water may be important sources of IAE.

The decision-making process of palliative care among male caregivers of chronically ill patients-A grounded theory study.

BACKGROUND: Family caregivers have a vital role to play in palliative care for chronically ill patients. In Taiwan, caregiver demographics are evolving, with the number of male caregivers increasing. Gender differences influence psychosocial behaviours, thought processes and communication styles. In healthcare, acknowledgement of gender differences facilitates effective delivery of high-quality care. AIM: The aim of this study is to explore male caregivers' decision-making process for palliative care for chronically ill family members. METHODS: This study employed grounded theory to generate a substantive theory of male caregivers' decision-making process for palliative care for chronically ill family members. We recruited 22 male participants from three inner-city teaching hospitals in Taiwan. FINDINGS: Regarding the decision-making process of palliative care of chronic ill family, where male caregivers do not want their loved ones suffering anymore, the male caregivers' decision-making process was impacted, first, by caregivers' views on the last stage of life; second, by their wish for good care during the end of life; and third, by their conviction that the patients' wishes should be respected. Furthermore, caregivers' philosophy of life and death is also a supportive ground for decision-making. This philosophy was influenced by their education in palliative care, financial status and religious beliefs and practices. The core category emerging from this study is encapsulated by a participant's assertion, 'How difficult is it? There are no male and female differences'. CONCLUSION: We found that palliative care experiences of male caregivers are important for the decision-making process for palliative care for their chronically ill family members. Caregivers want their loved ones to receive good care as the last step in life, to respect their wishes and no more suffering for the patient. Therefore, health professionals should be familiar with the palliative care process that caregivers go through to offer updated information when needed.

Association between maternal metabolic profiles in pregnancy, dietary patterns during lactation and breast milk leptin: a retrospective cohort study.

Breast milk leptin plays a potential role in preventing childhood obesity. However, the associations of breast milk leptin with maternal metabolism in pregnancy and dietary patterns during lactation are still unclear. We aimed to explore associations of breast milk leptin with maternal metabolic profiles in pregnancy and dietary patterns during lactation. A total of 332 participants were recruited for this retrospective cohort study. Breast milk samples were collected at approximately 6 weeks postpartum. Breast milk leptin and twenty-three metabolic profiles in pregnancy were measured in this study. A semi-quantitative FFQ was used to gather dietary information during lactation. Both principal component analysis and the diet balance index were used to derive dietary patterns. Among twenty-three maternal metabolic profiles, maternal serum glucose (ß = 1·61, P = 0·009), γ-glutamyl transferase (ß = 0·32, P = 0·047) and albumin (ß = -2·96, P = 0·044) in pregnancy were correlated with breast milk leptin. All dietary patterns were associated with breast milk leptin. Given the joint effects of maternal metabolism in pregnancy and dietary patterns during lactation, only diet quality distance was significantly associated with leptin concentrations in breast milk (low level v. almost no diet problem: ß = -0·46, P = 0·011; moderate/high level v. almost no diet problem: ß = -0·43, P = 0·035). In conclusion, both maternal metabolism in pregnancy and dietary patterns during lactation were associated with breast milk leptin. Maternal diet balance during lactation was helpful to improve breast milk leptin concentration.

Folate deficiency may increase the risk for elevated TSH in patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and thyroid dysfunction (TD) are two common chronic endocrine disorders that often coexist. Folate deficiency has been reported to be related with the onset and development of T2DM. However, the relationship between folate deficiency and TD remains unclear. This study aims to investigate the association of serum folate with TD in patients with T2DM. METHODS: The study used data on 268 inpatients with T2DM in the Beijing Chao-yang Hospital, Capital Medical University from October 2020 to February 2021. Thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), and serum folate were measured with chemiluminescence immunoassay (CLIA), and folate deficiency was defined as a serum folate concentration < 4.4 ng/mL. Ordinary least squares regression models were used to assess the association of serum folate with TSH concentration. Multivariable logistic regression models were performed to explore the correlation of folate deficiency and the risk for elevated TSH. RESULTS: 15.3% of T2DM patients had TD. Among those patients with TD, 80.5% had elevated TSH. Compared with the normal-TSH and low-TSH groups, the prevalence of folate deficiency was significantly higher in the elevated-TSH group (P < 0.001). Serum folate level was negatively associated with TSH (ß=-0.062, 95%CI: -0.112, -0.012). Folate deficiency was associated with the higher risk for elevated TSH in patients with T2DM (OR = 8.562, 95%CI: 3.108, 23.588). CONCLUSIONS: A low serum folate concentration was significantly associated with a higher risk for elevated TSH among T2DM patients.

Internet use, cardiometabolic multimorbidity, and death in older adults: a multi-cohort study spanning developing and developed countries.

BACKGROUND: Internet use is a double-edged sword for older adults' health. Whether internet use can prevent cardiometabolic diseases and death in older adults remains controversial. METHODS: Four cohorts across China, Mexico, the United States, and Europe were utilized. Internet use was defined using similar questions. Cardiometabolic diseases included diabetes, heart diseases, and stroke, with 2 or more denoting cardiometabolic multimorbidity. Depressive symptoms were assessed using the Center for Epidemiological Studies Depression Scale and Europe-depression scale. The competing risk analysis based on subdistribution hazard regression, random-effects meta-analysis, and mediation analysis were utilized. RESULTS: A total of 104,422 older adults aged 50 or older were included. Internet users (vs. digital exclusion) were at lower risks of diabetes, stroke, and death, with pooled sHRs (95% CIs) of 0.83 (0.74-0.93), 0.81 (0.71-0.92), and 0.67 (0.52-0.86), respectively, which remained significant in sensitivity analyses. The inverse associations of internet use with new-onset cardiometabolic diseases and death were progressively significant in Mexico, China, the United States, and Europe. For instance, older internet users in Europe were at 14-30% lower cardiometabolic risks and 40% lower risk of death. These associations were partially mediated by reduced depressive symptoms and were more pronounced in those with high socioeconomic status and women. Furthermore, patients with prior cardiometabolic conditions were at about 30% lower risk of death if they used the internet, which was also mediated by reduced depressive symptoms. However, certain cardiometabolic hazards of internet use in those aged < 65 years, with low socioeconomic status, men, and single ones were also observed. CONCLUSION: Enhancing internet usage in older adults can reduce depressive symptoms and thus reduce the risks of cardiometabolic diseases and death. The balance of internet use, socioeconomic status, and health literacy should be considered when popularizing the internet in older adults.

Association between household and outdoor air pollution and risk for metabolic syndrome among women in Beijing, China.

This study explored whether household and outdoor air pollution is associated with a greater risk for metabolic syndrome (MetS) among women. In all 11,860 women who cooked with clean energy were included in the analysis. Cooking frequency, range hood use during cooking, passive smoking exposure, and solid fuel use for heating were used to represent household air pollution. The 2-year average concentration of PM2.5, and face mask usage were used to reflect outdoor air pollution exposure. An index of air pollution exposure was also constructed. Multivariable logistic regression models were used to estimate the association between air pollution and risk for MetS, and a positive correlation was found. Our results indicated that household cooking used clean energy and exposure to a high level of outdoor PM2.5 without face mask usage may contribute to an increased risk for MetS among women.

Association between cooking fuel and folate insufficiency among pregnant women in Northern China.

This study explored whether using a coal or biomass stove for cooking was associated with a greater risk of red blood cell (RBC) folate insufficiency among pregnant women compared to using clean energy. A researcher-designed questionnaire was used to collect information on exposure-related factors and confounding factors. RBC folate concentrations were examined by microbiological assay. Binary logistic regression analysis was used to identify factors related to RBC folate insufficiency. The use of coal or firewood for cooking was associated with an increased risk of RBC folate insufficiency (<906 nmol/L) compared to gas. In subgroup analyses, associations between the use of polluting cooking fuels and folate insufficiency were positive for both urban and rural residents and statistically significant for rural women. Efforts to promote the use of clean energy and proper ventilation, especially in rural areas, are recommended to improve the health of pregnant women and their offspring.

Vitamin B12 and gestational diabetes mellitus: a systematic review and meta-analysis.

The relationship between vitamin B12 and gestational diabetes mellitus (GDM) remains controversial. To comprehensively evaluate the relationship between vitamin B12 and GDM, and to provide more information on GDM prevention, this study provides a systematic review and meta-analysis of vitamin B12 and GDM. As of September 22, 2021, 304 articles were searched in PubMed, Web of Science, EMBASE, and Cochrane databases, of which 15 studies met the inclusion criteria. Results presented there was no association between maternal vitamin B12 concentration during the first trimester with GDM, however, low vitamin B12 concentration in the second or third trimester of pregnancy was related to an increased risk of GDM. Compared with the non-GDM group, the vitamin B12 concentration in the GDM group was remarkably decreased (MD: -10·79; 95%CI: -21·37, -0·21), and vitamin B12 deficiency increased the risk for GDM (OR: 1·59; 95%CI: 1·10, 2·29). These effects were more significant among Asians. In addition, an increased ratio of high folate to low vitamin B12 in serum also increased the risk of GDM (OR: 1·87; 95% CI: 1·46, 2·41). These results suggest that more vitamin B12 may need to be provided during pregnancy.

Elevated concentrations of chromium in maternal serum, umbilical cord serum, and cord tissue are associated with an increased risk for orofacial clefts.

Chromium (Cr) exposure during gestation causes malformations in animal experiments. In this multicenter case-control study, we initially involved 130 orofacial clefts (OFCs) and 260 controls to assess the association between Cr concentration and risk for OFCs. Then, umbilical cord serum (49 vs. 119) and cord tissue (84 vs. 142) were used to validate the association between Cr and OFCs. We found that maternal serum Cr concentrations in OFC cases were significantly higher than those in controls. Compared with the lowest tertile of maternal serum Cr concentration, the highest tertile of Cr increased the risk for OFCs [OR = 2.14 (1.14-4.05)]. In the validation cohort of umbilical cord serum and tissue, higher concentrations of Cr were associated with increased risks for OFCs in a dose-dependent manner (all Ps for trends <0.05). Cr concentrations in maternal serum and cord serum showed a positive correlation. The Cr concentration in cord serum was inversely correlated with egg and milk consumption frequencies, and the Cr concentration in cord tissue was positively associated with indoor coal burning. In conclusion, prenatal Cr exposure is a risk factor for OFCs, and indoor coal burning during pregnancy may be one of the sources of Cr exposure.

Maternal exposure to heavy metals and risk for severe congenital heart defects in offspring.

BACKGROUND: Congenital heart defects (CHDs) are the most common congenital malformations with a complex etiology, and environmental factors play an important role. Large epidemiology studies on prenatal exposure to selected heavy metals and their association with risk for CHDs are scarce and joint effects are not well understood. OBJECTIVES: To examine the association between prenatal exposure to selected heavy metals and risk for CHDs. METHODS: Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the maternal plasma concentrations of arsenic, cadmium, mercury, lead, and manganese were in 303 CHD cases and 303 healthy controls that were recruited in eight hospitals in China. Generalized linear mixed model (GLMM) and Bayesian kernel machine regression (BKMR) were fitted to evaluate the individual and joint effects of metal concentrations on CHDs. RESULTS: In GLMM, two metals were each significantly associated with an increased risk for CHDs [adjusted odds ratio (95% confidence interval): mercury, 2.88 (1.22-6.77); lead, 2.74 (1.00-7.57)]. In BKMR, CHD risk increased with mixture levels of the five metals when their concentrations were at the 40th percentile or higher, compared to when all metals were below their 35th percentile, and mercury was the major metal that contributed to the mixture effect. The interaction between mercury and lead was observed in BKMR. CONCLUSIONS: Using metal concentrations in maternal plasma obtained during the second or third trimester as exposure markers, we found that the risk of CHDs increased with the levels of the mixtures of As, Cd, Hg, Pb, and Mn, with Hg being the most important contributor to the mixture effect.

Families of Patients With Cancer: Responses and Actions to People With Cancer Who Use Complementary and Alternative Medicine: A Qualitative Study in Taiwan.

This study aims to explore how the families of patients with cancer respond to and act toward complementary and alternative medicine (CAM) use. A qualitative research design based on grounded theory was adopted in this study. Semistructured and face-to-face in-depth interviews were conducted. Each participant was involved in a one-to-one individual interview. Five categories emerged regarding how the families of patients with cancer responded to and acted toward CAM use: purposes of using CAM, CAM use between patients and families, role of family caregivers, actions when using CAM, and seeking religious practice. The core category following coding emphasized the paramount importance of patients' comfort. The findings revealed that the families of patients with cancer may respond and act differently regarding patients' use of CAM. During this process, patients may not inform family members that they are using CAM. Health care professionals should consider this in their interactions with family members.

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.

Hypermethylation of WNT3A gene and non-syndromic cleft lip and/or palate in association with in utero exposure to lead: A mediation analysis.

OBJECTIVES: We aim to investigate association between WNT3A methylation and risk of non-syndromic cleft lip and/or palate (NSCL/P), and examine mediating effect of WNT3A methylation on the association of NSCL/P and lead (Pb) exposure in fetuses. METHODS: DNA methylation of WNT3A in umbilical cord blood was determined among 59 NSCL/P cases and 118 non-malformed controls. Mediation analysis was performed to evaluate the potential mediating effect of WNT3A methylation on association between concentrations of Pb in umbilical cord and risk for NSCL/P. Additionally, an animal experiment in which cleft palates were induced by lead acetate was conducted. RESULTS: The overall average methylation level of WNT3A was significant higher in NSCL/P cases as compared to controls. The risk for NSCL/P was increased by 1.90-fold with hypermethylation of WNT3A. Significant correlation was observed between concentrations of Pb in umbilical cord and methylation level of WNT3A. The hypermethylation of WNT3A had a mediating effect by 9.32% of total effect of Pb on NSCL/P risk. Gender-specific association between WNT3A methylation and NSCL/P was observed in male fetuses, and the percentage of the mediating effect increased to 14.28%. Animal experiment of mice showed that maternal oral exposure to lead acetate may result in cleft palate in offspring. CONCLUSION: Hypermethylation of WNT3A was associated with the risk for NSCL/P and may be partly explain the association between exposure to Pb and risk for NSCL/P. The teratogenic and fetotoxic effects of Pb were found in mice.

Association of gestational weight gain rate with infant anaemia in China: a birth cohort study.

Excessive gestational weight gain (GWG) increases the risk of maternal anaemia during pregnancy, but whether it is associated with offspring anaemia has not been investigated. We aimed to prospectively investigate the association of GWG rate in the second/third trimester with infant Hb concentration and anaemia risk. The present study comprised 13 765 infants born during 2006-2009 to mothers who participated in a trial on prenatal micronutrient supplementation. The GWG was calculated by subtracting the maternal weight at enrolment from that at end-pregnancy. The GWG rate was calculated as dividing the GWG by number of weeks between the two measurements and classified into quintiles within each category of maternal BMI. Infant Hb concentrations were measured at 6 and 12 months of age, and anaemia was defined as an Hb concentration <110 g/l. Of the 13 765 infants, 949 (6·9 %) were anaemic at 6 months and 728 (5·3 %) at 12 months. The GWG rate was inversely and linearly associated with the infant Hb concentrations at both 6 and 12 months (P < 0·001 for linearity). Compared with the middle quintile of GWG rate, the highest quintile was associated with an increased risk of anaemia at 6 months (adjusted OR 1·30, 95 % CI 1·07, 1·59) and 12 months (adjusted OR 1·74, 95 % CI 1·40, 2·17). The associations were consistently mediated by maternal anaemia during pregnancy (P < 0·001). In conclusion, excessive GWG rate appears to be associated with an increased risk of infant anaemia, partly independent of maternal anaemia during pregnancy that mediates the association.

Rate of gestational weight gain and adverse pregnancy outcomes in rural nulliparous women: a prospective cohort analysis from China.

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.

Folate of pregnant women after a nationwide folic acid supplementation in China.

Folate insufficiency during the periconceptional period increases the risk of neural tube defects (NTDs) in offspring, and folic acid supplementation substantially reduces the risk. Widespread large-scale folic acid supplementation (0.4-mg folic acid tablet) has been adopted as a main strategy to prevent NTDs in China since 2009. We examined folate concentrations in plasma and red blood cells (RBCs) of pregnant women and the factors associated with blood folate concentrations in a population with a high prevalence of NTDs in northern China. A cross-sectional survey was conducted in 2014, and 1,107 pregnant women were recruited from 11 county or city maternal and child health centres across Shanxi province. Microbiological assays were used to determine folate concentrations. Factors associated with blood folate insufficiency were identified. The median (25th and 75th percentiles) folate concentrations were 28.4 (17.6, 45.2) nmol L-1 and 1,001.2 (658.7, 1,402.5) nmol L-1 in plasma and RBCs, respectively. According to the proposed RBC (906 nmol L-1 ) concentrations for optimal NTD prevention, 42.4% participants had RBC folate insufficiency. Rural women had a higher proportion of folate insufficiency than urban women. Folic acid supplementation was the only factor associated with RBC folate insufficiency. A large proportion of women had RBC folate concentrations that are not optimal for the prevention of NTDs despite free access to folic acid supplements. Actions that aim to improve folic acid supplementation compliance are needed to reach the full potential of the nationwide folic acid supplementation programme in terms of NTD prevention.

Secondhand smoke during the periconceptional period increases the risk for orofacial clefts in offspring.

BACKGROUND: To examine whether exposure to secondhand smoke (SHS) during the periconceptional period among nonsmoking women is associated with an increased risk for orofacial clefts (OFCs) in offspring in a population with low rates of maternal active smoking but high rates of SHS exposure. METHODS: We recruited 240 women with OFC-affected pregnancies and 1420 women who delivered healthy infants from a population-based case-control study in northern China during 2002 and 2016. Data including self-reported SHS exposure were collected by trained health care workers through face-to-face interviews. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to estimate the association between SHS exposure and OFC risk. RESULTS: The unadjusted ORs for OFCs and cleft lip with or without cleft palate (CL±P) in association with SHS exposure were both 1.6 (95% CI 1.2, 2.1). After adjusting for maternal fever or flu, farming occupation, infant sex, and history of pregnancy affected by birth defects, the adjusted ORs were both 1.6 (95% CI 1.2, 2.2). Frequent SHS exposure (>6 times/week) was associated with an even higher risk for OFCs (adjusted OR 2.6, 95% CI 1.8, 3.8) and for CL±P (adjusted OR 2.5, 95% CI 1.7, 3.7). CONCLUSIONS: Maternal SHS exposure during the periconceptional period increases the risk for OFCs in offspring among nonsmoking mothers.

Umbilical Cord Concentrations of Selected Heavy Metals and Risk for Orofacial Clefts.

Although arsenic (As), cadmium (Cd), lead (Pb), and nickel (Ni) have the ability to induce orofacial clefts (OFCs) in rodents, evidence is absent from human epidemiological investigations with markers of in utero exposure. We investigated the associations between concentrations of As, Cd, Pb, and Ni in umbilical cord tissues and risk of OFCs, and the interactions between each pair of metals on OFC risk in a case-control study. Umbilical cord concentrations of metals were determined by inductively coupled plasma mass spectrometry in 92 OFC cases and 200 nonmalformed controls. Concentrations above the median of all subjects was associated with an elevated OFC risk of 8.36-fold for As, 7.22-fold for Cd, 15.32-fold for Pb, and 6.79-fold for Ni. Concentrations of As, Cd, Pb, and Ni were also associated with risks for OFC subtypes. When metal concentrations were divided into tertiles by levels of metal concentrations of all subjects, dose-response relationships of risks for total OFCs and subtypes with As, Cd, Pb, and Ni concentrations were demonstrated. Significant synergistic interaction between As and Ni on the risk of OFCs was also observed. Therefore, elevated in utero exposure to As, Cd, Pb, and Ni may increase the risks of OFCs in newborns.

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.