Association between maternal folate concentrations during pregnancy and insulin resistance in Indian children.
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ABSTRACT: Aims/hypothesis
In an Indian birth cohort, higher maternal homocysteine concentration in pregnancy was associated with lower birthweight of the offspring. Lower maternal vitamin B12 and higher folate concentrations were associated with higher offspring insulin resistance. Disordered one-carbon metabolism during early development may increase later metabolic risk. We explored these associations in another birth cohort in India at three age points.Methods
We measured plasma vitamin B12, folate and homocysteine concentrations at 30 ± 2 weeks' gestation in 654 women who delivered at one hospital. Neonatal anthropometry was recorded, and the children's glucose and insulin concentrations were measured at 5, 9.5 and 13.5 years of age. Insulin resistance was estimated using HOMA of insulin resistance (HOMA-IR).Results
Maternal homocysteine concentrations were inversely associated with all neonatal anthropometric measurements (p < 0.05), and positively associated with glucose concentrations in the children at 5 (30 min; p = 0.007) and 9.5 years of age (120 min; p = 0.02). Higher maternal folate concentrations were associated with higher HOMA-IR in the children at 9.5 (p = 0.03) and 13.5 years of age (p = 0.03). Maternal vitamin B12 concentrations were unrelated to offspring outcomes.Conclusions/interpretation
Maternal vitamin B12 status did not predict insulin resistance in our cohort. However, associations of maternal homocysteine and folate concentrations with birth size, and with childhood insulin resistance and glycaemia in the offspring, suggest a role for nutritionally driven disturbances in one-carbon metabolism in fetal programming of diabetes.
SUBMITTER: Krishnaveni GV
PROVIDER: S-EPMC3855580 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Aims/hypothesisRaised maternal plasma total homocysteine (tHcy) concentrations predict small size at birth, which is a risk factor for type 2 diabetes mellitus. We studied the association between maternal vitamin B12, folate and tHcy status during pregnancy, and offspring adiposity and insulin resistance at 6 years.MethodsIn the Pune Maternal Nutrition Study we studied 700 consecutive eligible pregnant women in six villages. We measured maternal nutritional intake and circulating concentrations of folate, vitamin B12, tHcy and methylmalonic acid (MMA) at 18 and 28 weeks of gestation. These were correlated with offspring anthropometry, body composition (dual-energy X-ray absorptiometry scan) and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-R]) at 6 years.ResultsTwo-thirds of mothers had low vitamin B12 (<150 pmol/l), 90% had high MMA (>0.26 micromol/l) and 30% had raised tHcy concentrations (>10 micromol/l); only one had a low erythrocyte folate concentration. Although short and thin (BMI), the 6-year-old children were relatively adipose compared with the UK standards (skinfold thicknesses). Higher maternal erythrocyte folate concentrations at 28 weeks predicted higher offspring adiposity and higher HOMA-R (both p < 0.01). Low maternal vitamin B12 (18 weeks; p = 0.03) predicted higher HOMA-R in the children. The offspring of mothers with a combination of high folate and low vitamin B12 concentrations were the most insulin resistant.Conclusions/interpretationLow maternal vitamin B12 and high folate status may contribute to the epidemic of adiposity and type 2 diabetes in India.
| S-EPMC2100429 | biostudies-literature
Project description:Previous reports have linked maternal prepregnancy obesity with low folate concentrations and child overweight or obesity (OWO) in separate studies. To our knowledge, the role of maternal folate concentrations, alone or in combination with maternal OWO, in child metabolic health has not been examined in a prospective birth cohort.To test the hypotheses that maternal folate concentrations can significantly affect child metabolic health and that sufficient maternal folate concentrations can mitigate prepregnancy obesity-induced child metabolic risk.This prospective birth cohort study was conducted at the Boston Medical Center, Boston, Massachusetts. It included 1517 mother-child dyads recruited at birth from 1998 to 2012 and followed up prospectively up to 9 years from 2003 to 2014.Child body mass index z score calculated according to US reference data, OWO defined as a body mass index in the 85th percentile or greater for age and sex, and metabolic biomarkers (leptin, insulin, and adiponectin).The mean (SD) age was 28.6 (6.5) years for mothers and 6.2 (2.4) years for the children. An L-shaped association between maternal folate concentrations and child OWO was observed: the risk for OWO was higher among those in the lowest quartile (Q1) as compared with those in Q2 through Q4, with an odds ratio of 1.45 (95% CI, 1.13-1.87). The highest risk for child OWO was found among children of obese mothers with low folate concentrations (odds ratio, 3.05; 95% CI, 1.91-4.86) compared with children of normal-weight mothers with folate concentrations in Q2 through Q4 after accounting for multiple covariables. Among children of obese mothers, their risk for OWO was associated with a 43% reduction (odds ratio, 0.57; 95% CI, 0.34-0.95) if their mothers had folate concentrations in Q2 through Q4 compared with Q1. Similar patterns were observed for child metabolic biomarkers.In this urban low-income prospective birth cohort, we demonstrated an L-shaped association between maternal plasma folate concentrations and child OWO and the benefit of sufficient folate concentrations, especially among obese mothers. The threshold concentration identified in this study exceeded the clinical definition of folate deficiency, which was primarily based on the hematological effect of folate. Our findings underscore the need to establish optimal rather than minimal folate concentrations for preventing adverse metabolic outcomes in the offspring.
| S-EPMC5147730 | biostudies-literature
Project description:Several studies assessed the association of maternal folate intake with infant asthma risk, but the findings are controversial. We performed a meta-analysis to clarify the association between maternal folate intake and infant asthma risk. PubMed and SCOPUS databases were searched for related studies published until August 2018. Fixed-effects models were applied to pool relative risks (RRs) and their corresponding 95% confidence intervals (CIs) due to the low heterogeneity. We also adopted generalized least-squares trend (GLST) estimation for the dose-response analysis. In our study, a total of 10 studies with maternal folate intake and 5 studies with blood folate concentration were included. We found that maternal folate intake during pregnancy was significantly related to the risk of infant asthma (RR?=?1.11; 95% CI?=?1.06-1.17). Similar results were found for geographic region from Europe (RR?=?1.08; 95% CI?=?1.01-1.16) and North America (RR?=?1.20; 95% CI?=?1.11-1.30) in subgroup analyses. Meanwhile, the dose-response analysis showed a linear relationship between maternal folic acid intake during pregnancy and infant asthma risk. This meta-analysis indicates that maternal folate intake during pregnancy could increase infant asthma risk. Therefore, the adverse effect of folic acid on infant asthma should not be ignored when it is supplemented during pregnancy to prevent birth defects.
| S-EPMC6554315 | biostudies-literature
Project description:Studies on the association between maternal folate status and gestational diabetes mellitus (GDM) have yielded inconsistent results. This meta-analysis was performed to determine whether there may exist some association between maternal folate status and GDM. Unrestricted searches of PubMed, Web of Science, Cochrane, and Embase were conducted. All relevant studies on the association between maternal folat status and GDM risk were screened. The standardized mean difference (SMD) with 95% CIs was used to determine the association between maternal folate and GDM. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models to assess the impact of maternal folate status on GDM risk. 12 studies were included. The overall data revealed that compared with the non-GDM group, women with GDM had higher level of folate (SMD 0.41, 95% CI 0.07 to 0.21, I2 = 17.2%) in second or third trimester. We also found that maternal high folate status may be associated with increased risk of GDM (OR 2.16, 95% CI 1.70 to 2.74, I2 = 0.0%). Compared with non-GDM group, women with GDM are prone to higher folate level. Moreover, high maternal folate status may predict a higher risk of GDM. As the number of included studies was limited, further large population studies are needed in the future.
| S-EPMC8020922 | biostudies-literature
Project description:The aim of our study was to determine whether the use of iron supplements during pregnancy affects the risk for celiac disease in children.We assessed data from the prospective Norwegian Mother and Child cohort study, in which individuals with celiac disease were identified by answers on questionnaires and linkage to the Norwegian Patient Register. Complete data were available for 78,846 children (mean age 5.9 years, range 2-12 years); 314 children were identified with celiac disease. Questionnaires were given to pregnant women to collect information on use of iron-containing supplements, diet, anemia, and levels of hemoglobin.Celiac disease was diagnosed in 4.65 of 1000 children whose mothers took iron supplements while they were pregnant, compared with 3.15 of 1000 children whose mothers did not. After adjusting for children's age, sex, and age of gluten introduction, and the presence of celiac disease in mothers, iron supplementation during pregnancy remained significantly associated with celiac disease in children (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.05-1.68; P = .019). However, celiac disease was not associated with the mothers' intake of iron from foods (adjusted OR, 1.00; 95% CI, 0.97-1.03). Anemia before or during the early stages of pregnancy was not significantly associated with the risk of celiac disease in children (adjusted OR, 1.24; 95% CI, 0.84-2.00; P = .24). The use of iron supplements during pregnancy remained significantly associated with celiac disease in children after adjusting for children who were given iron supplements before 18 months of age, which itself was associated with celiac disease.In a prospective Norwegian Mother and Child cohort study, we found an increased risk of celiac disease in children whose mothers used iron supplements during pregnancy; this association does not appear to arise from maternal anemia.
| S-EPMC3984974 | biostudies-literature
Project description:Objectives Viral bronchiolitis is the most common cause of infant hospitalization. Folic acid supplementation is important during the periconceptional period to prevent neural tube defects. An area of investigation is whether higher prenatal folate is a risk factor for childhood respiratory illnesses. We investigated the association between maternal 2nd trimester plasma folate levels and infant bronchiolitis. Methods We conducted a retrospective cohort analysis in a subset of mother-infant dyads (n?=?676) enrolled in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study and Tennessee Medicaid. Maternal folate status was determined using 2nd trimester (16-28 weeks) plasma samples. Bronchiolitis diagnosis in the first year of life was ascertained using International Classification of Diagnosis-9 codes from Medicaid administrative data. We used multivariable logistic regression to assess the adjusted association of prenatal folate levels and infant bronchiolitis outcome. Results Half of the women in this lower-income and predominately African-American (84%) study population had high levels of folate (median 2nd trimester level 19.2 ng/mL) and 21% of infants had at least one bronchiolitis healthcare visit. A relationship initially positive then reversing between maternal plasma folate and infant bronchiolitis was observed that did not reach statistical significance (poverall?=?.112, pnonlinear effect?=?.088). Additional adjustment for dietary methyl donor intake did not significantly alter the association. Conclusions for Practice Results did not confirm a statistically significant association between maternal 2nd trimester plasma folate levels and infant bronchiolitis. Further work is needed to investigate the role of folate, particularly higher levels, in association with early childhood respiratory illnesses.
| S-EPMC6339607 | biostudies-literature
Project description:Prenatal tobacco smoke exposure may be associated with low maternal folate levels that increase the risk of adverse infant and child health outcomes by reducing folate availability during fetal development.Using data from the Health Outcomes and Measures of the Environment Study, we examined the relationship between secondhand or active tobacco smoke exposure and whole blood folate concentrations in pregnant women from Cincinnati, Ohio (n = 362) at approximately 16-week gestation. We used multivariable linear regression to examine the association between continuous or categorical serum cotinine levels and whole blood folate levels, adjusting for sociodemographic, dietary, and perinatal variables.After adjustment for potential confounders, an interquartile range increases in serum cotinine concentration (0.012-0.224 ng/mL) was suggestively associated with decreased whole blood folate levels (?, -23 nmol/L; 95% confidence interval (CI), -49, 3; P value = .08). Compared with unexposed women, reductions in mean whole blood folate were observed among active smokers (?, -94, 95% CI, 195, 6 nmol/L; P value = .40); smaller reductions were observed among women with secondhand exposure (?, 26; CI, 84, 32 nmol/L; P value = .07).Consistent with prior studies, active smoking was associated with reduced whole blood folate levels among these pregnant women. Secondhand tobacco smoke exposures were associated with small and imprecise reductions in whole blood folate levels.
| S-EPMC4071615 | biostudies-literature
Project description:Maternal smoking during pregnancy has been consistently related to low birthweight. However, older mothers, who are already at risk of giving birth to low birthweight infants, might be even more susceptible to the effects of maternal smoking. Therefore, this study aimed to examine the modified association between maternal smoking and low birthweight by maternal age.Data were obtained from a questionnaire survey of all mothers of children born between 2004 and 2010 in Okinawa, Japan who underwent medical check-ups at age 3 months. Variables assessed were maternal smoking during pregnancy, maternal age, gestational age, parity, birth year, and complications during pregnancy. Stratified analyses were performed using a logistic regression model.In total, 92641 participants provided complete information on all variables. Over the 7 years studied, the proportion of mothers smoking during pregnancy decreased from 10.6% to 5.0%, while the prevalence of low birthweight did not change remarkably (around 10%). Maternal smoking was significantly associated with low birthweight in all age groups. The strength of the association increased with maternal age, both in crude and adjusted models.Consistent with previous studies conducted in Western countries, this study demonstrates that maternal age has a modifying effect on the association between maternal smoking and birthweight. This finding suggests that specific education and health care programs for older smoking mothers are important to improve their foetal growth.
| S-EPMC4721610 | biostudies-other
Project description:Single nucleotide polymorphisms and pre- and peri-conception folic acid (FA) supplementation and dietary data were used to identify one-carbon metabolic factors associated with pregnancy outcomes in 3196 nulliparous women. In 325 participants, we also measured circulating folate, vitamin B12 and homocysteine. Pregnancy outcomes included preeclampsia (PE), gestational hypertension (GHT), small for gestational age (SGA), spontaneous preterm birth (sPTB) and gestational diabetes mellitus (GDM). Study findings show that maternal genotype MTHFR A1298C(CC) was associated with increased risk for PE, whereas TCN2 C766G(GG) had a reduced risk for sPTB. Paternal MTHFR A1298C(CC) and MTHFD1 G1958A(AA) genotypes were associated with reduced risk for sPTB, whereas MTHFR C677T(CT) genotype had an increased risk for GHT. FA supplementation was associated with higher serum folate and vitamin B12 concentrations, reduced uterine artery resistance index and increased birth weight. Women who supplemented with <800 ?g daily FA at 15-week gestation had a higher incidence of PE (10.3%) compared with women who did not supplement (6.1%) or who supplemented with ?800 ?g (5.4%) (P < .0001). Higher serum folate levels were found in women who later developed GDM compared with women with uncomplicated pregnancies (Mean ± SD: 37.6 ± 8 nmol L-1 vs. 31.9 ± 11.2, P = .007). Fast food consumption was associated with increased risk for developing GDM, whereas low consumption of green leafy vegetables and fruit were independent risk factors for SGA and GDM and sPTB and SGA, respectively. In conclusion, maternal and paternal genotypes, together with maternal circulating folate and homocysteine concentrations, and pre- and early-pregnancy dietary factors, are independent risk factors for pregnancy complications.
| S-EPMC7729528 | biostudies-literature
Project description:ObjectiveTo examine the effect of maternal folic acid supplementation and maternal plasma folate and antiepileptic drug (AED) concentrations on language delay in AED-exposed children of mothers with epilepsy.MethodsChildren of mothers with and without epilepsy enrolled from 1999 to 2008 in the Norwegian Mother and Child Cohort study were included. Information on medical history, AED use, and folic acid supplementation during pregnancy was collected from parent-completed questionnaires. Maternal plasma folate and maternal plasma and umbilical cord AED concentrations were measured in blood samples from gestational weeks 17 to 19 and immediately after birth, respectively. Language development at 18 and 36 months was evaluated by the Ages and Stages Questionnaires.ResultsA total of 335 AED-exposed children of mothers with epilepsy and 104,222 children of mothers without epilepsy were surveyed. For those with no maternal periconceptional folic acid supplementation, the fully adjusted odds ratio (OR) for language delay in AED-exposed children compared to the controls at 18 months was 3.9 (95% confidence interval [CI] 1.9-7.8, p < 0.001) and at 36 months was 4.7 (95% CI 2.0-10.6, p < 0.001). When folic supplementation was used, the corresponding ORs for language delay were 1.7 (95% CI 1.2-2.6, p = 0.01) and 1.7 (95% CI 0.9-3.2, p = 0.13), respectively. The positive effect of folic acid supplement use on language delay in AED-exposed children was significant only when supplement was used in the period from 4 weeks before the pregnancy and until the end of the first trimester.ConclusionFolic acid use early in pregnancy may have a preventive effect on language delay associated with in utero AED exposure.
| S-EPMC6133626 | biostudies-literature