Maternal Serum Vitamin B12 during Pregnancy and Offspring Autism Spectrum Disorder.
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ABSTRACT:
SUBMITTER: Sourander A
PROVIDER: S-EPMC10146734 | biostudies-literature | 2023 Apr
REPOSITORIES: biostudies-literature
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Maternal Serum Vitamin B12 during Pregnancy and Offspring Autism Spectrum Disorder.
Sourander Andre A Silwal Sanju S Silwal Sanju S Surcel Heljä-Marja HM Hinkka-Yli-Salomäki Susanna S Upadhyaya Subina S McKeague Ian W IW Cheslack-Postava Keely K Brown Alan S AS
Nutrients 20230421 8
This study examined the association between maternal serum vitamin B12 levels during early pregnancy and offspring autism spectrum disorders (ASD) and subtypes. Based on a Finnish national birth cohort, case offspring <i>(n</i> = 1558) born in 1987-2007 and diagnosed with ASD by 2015 were matched with one control on date of birth, sex and place of birth. Maternal vitamin B12 levels were measured during first and early second trimesters of pregnancy. High maternal vitamin B12 levels (≥81th percen ...[more]
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Project description:BackgroundFindings from previous studies on maternal 25-hydroxyvitamin D [25(OH)D] levels during pregnancy and autism spectrum disorder (ASD) in offspring are inconsistent.MethodsThe association between maternal 25(OH)D levels during pregnancy and offspring ASD was examined using data from a nationwide population-based register with a nested case-control study design. The ASD cases (n = 1558) were born between 1987 and 2004 and received a diagnosis of ASD by 2015; cases were matched with an equal number of controls. Maternal 25(OH)D levels during pregnancy were measured using quantitative immunoassay from maternal sera collected during the first and early second trimesters and archived in the national biobank of the Finnish Maternity Cohort. Conditional logistic regression examined the association between maternal 25(OH)D levels and offspring ASD.ResultsIn the adjusted model, there was a significant association between increasing log-transformed maternal 25(OH)D levels and decreasing risk of offspring ASD (adjusted odds ratio [aOR] 0.75, 95% confidence interval [CI] 0.62-0.92, p = .005). Analyses by quintiles of maternal 25(OH)D levels revealed increased odds for ASD in the 2 lowest quintiles, <20 (aOR 1.36, 95% CI 1.03-1.79, p = .02) and 20-39 (aOR 1.31, 95% CI 1.01-1.70, p = .04), compared with the highest quintile. The increased risk of ASD was observed in association with deficient (<30 nmol/L) (aOR 1.44, 95% CI 1.15-1.81, p = .001) and insufficient (30-49.9 nmol/L) maternal 25(OH)D levels (aOR 1.26, 95% CI 1.04-1.52, p = .01) compared with sufficient levels.ConclusionsThis finding has implications for understanding the role of maternal vitamin D during fetal brain development and increased risk of ASD.
| S-EPMC8752030 | biostudies-literature
Project description:BackgroundPreviously, numerous epidemiologic studies reported an association between autism spectrum disorder (ASD) and exposure to air pollution during pregnancy. However, there have been no metabolomics studies investigating the impact of pregnancy pollution exposure to ASD risk in offspring.ObjectivesTo identify differences in maternal metabolism that may reflect a biological response to exposure to high air pollution in pregnancies of offspring who later did or did not develop ASD.MethodsWe obtained stored mid-pregnancy serum from 214 mothers who lived in California's Central Valley and experienced the highest levels of air pollution during early pregnancy. We estimated each woman's average traffic-related air pollution exposure (carbon monoxide, nitric oxides, and particulate matter <2.5 μm) during the first trimester using the California Line Source Dispersion Model, version 4 (CALINE4). By utilizing liquid chromatography-high resolution mass spectrometry, we identified the metabolic profiles of maternal serum for 116 mothers with offspring who later developed ASD and 98 control mothers. Partial least squares discriminant analysis (PLS-DA) was employed to select metabolic features associated with air pollution exposure or autism risk in offspring. We also conducted extensive pathway enrichment analysis to elucidate potential ASD-related changes in the metabolome of pregnant women.ResultsWe extracted 4022 and 4945 metabolic features from maternal serum samples in hydrophilic interaction (HILIC) chromatography (positive ion mode) and C18 (negative ion mode) columns, respectively. After controlling for potential confounders, we identified 167 and 222 discriminative features (HILIC and C18, respectively). Pathway enrichment analysis to discriminate metabolic features associated with ASD risk indicated various metabolic pathway perturbations linked to the tricarboxylic acid (TCA) cycle and mitochondrial function, including carnitine shuttle, amino acid metabolism, bile acid metabolism, and vitamin A metabolism.ConclusionUsing high resolution metabolomics, we identified several metabolic pathways disturbed in mothers with ASD offspring among women experiencing high exposure to traffic-related air pollution during pregnancy that were associated with mitochondrial dysfunction. These findings provide us with a better understanding of metabolic disturbances involved in the development of ASD under adverse environmental conditions.
| S-EPMC9059845 | biostudies-literature
Project description:BackgroundAutism spectrum disorder (ASD) evolves from an interplay between genetic and environmental factors during prenatal development. Since identifying maternal biomarkers associated with ASD risk in offspring during early pregnancy might result in new strategies for intervention, we investigated maternal metabolic biomarkers in relation to occurrence of ASD in offspring using both univariate logistic regression and multivariate network analysis.MethodsSerum samples from 100 women with an offspring diagnosed with ASD and 100 matched control women with typically developing offspring were collected at week 14 of pregnancy. Concentrations of 62 metabolic biomarkers were determined, including amino acids, vitamins (A, B, D, E, and K), and biomarkers related to folate (vitamin B9) metabolism, lifestyle factors, as well as C-reactive protein (CRP), the kynurenine-tryptophan ratio (KTR), and neopterin as markers of inflammation and immune activation.ResultsWe found weak evidence for a positive association between higher maternal serum concentrations of folate and increased occurrence of ASD (OR per 1 SD increase: 1.70, 95% CI 1.22-2.37, FDR adjusted P = 0.07). Multivariate network analysis confirmed expected internal biochemical relations between the biomarkers. Neither inflammation markers nor vitamin D3 levels, all hypothesized to be involved in ASD etiology, displayed associations with ASD occurrence in the offspring.ConclusionsOur findings suggest that high maternal serum folate status during early pregnancy may be associated with the occurrence of ASD in offspring. No inference about physiological mechanisms behind this observation can be made at the present time because blood folate levels may have complex relations with nutritional intake, the cellular folate status and status of other B-vitamins. Therefore, further investigations, which may clarify the potential role and mechanisms of maternal blood folate status in ASD risk and the interplay with other potential risk factors, in larger materials are warranted.
| S-EPMC6964211 | biostudies-literature
Project description:BackgroundThere has been a growing interest in the association between maternal levels of vitamin D during pregnancy and offspring autism. However, whether any associations reflect causal effects is still inconclusive.MethodsWe used data from a UK-based pregnancy cohort study (Avon Longitudinal Study of Parents and Children) comprising 7689 births between 1991 and 1992 with maternal blood vitamin D levels recorded during pregnancy and at least one recorded outcome measure, including autism diagnosis and autism-associated traits. The association between each outcome with seasonal and gestational age-adjusted maternal serum 25-hydroxyvitamin D during pregnancy was estimated using confounder-adjusted regression models. Multiple imputation was used to account for missing data, and restricted cubic splines were used to investigate nonlinear associations. Mendelian randomization was used to strengthen causal inference.ResultsNo strong evidence of an association between maternal serum 25-hydroxyvitamin D during pregnancy and any offspring autism-associated outcome was found using multivariable regression analysis (autism diagnosis: adjusted OR = 0.98, 95% CI = 0.90-1.06), including with multiple imputation (autism diagnosis: adjusted OR = 0.99, 95% CI = 0.93-1.06), and no evidence of a causal effect was suggested by Mendelian randomization (autism diagnosis: causal OR = 1.08, 95% CI = 0.46-2.55). Some evidence of increased odds of autism-associated traits at lower levels of maternal serum 25-hydroxyvitamin D was found using spline analysis.LimitationsOur study was potentially limited by low power, particularly for diagnosed autism cases as an outcome. The cohort may not have captured the extreme lows of the distribution of serum 25-hydroxyvitamin D, and our analyses may have been biased by residual confounding and missing data.ConclusionsThe present study found no strong evidence of a causal link between maternal vitamin D levels in pregnancy and offspring diagnosis or traits of autism.
| S-EPMC9652971 | biostudies-literature
Project description:Lay abstractAutism spectrum disorder is heterogeneous and often accompanied by co-occurring conditions. Previous studies have shown that maternal health conditions during pregnancy including obesity, diabetes, preeclampsia, and asthma were associated with increased likelihood of autism. However, little has been done examining the likelihood associated with autism with co-occurring conditions. This study assessed these maternal health conditions in relationship to autism and gastrointestinal disturbances, a common co-occurring condition in children diagnosed with autism. Data included 308,536 mother-child pairs from one integrated health care system with comprehensive electronic medical records. Among the study cohort, 5,131 (1.7%) children had a diagnosis of autism by age 5. Gastrointestinal disturbances were present in 35.4% of children diagnosed with autism and 25.1% of children without autism diagnoses. Our results showed that each of the four maternal health conditions during pregnancy was associated with increased likelihood of gastrointestinal disturbances, autism without gastrointestinal disturbances, and autism with gastrointestinal disturbances. For all four maternal health conditions, the association was greatest for likelihood of autism with gastrointestinal disturbances. Given that children diagnosed with autism are more likely to have gastrointestinal disturbances and over 80% of gastrointestinal disturbances in this cohort were diagnosed prior to autism diagnosis, this study suggests that there may be common biological pathways between autism and gastrointestinal disturbances impacted by these maternal exposures. Future studies are warranted to assess associations between different exposures and autism with other co-occurring conditions to increase our understanding of autism heterogeneity.
| S-EPMC9984567 | biostudies-literature
Project description:Evidence supports no link between maternal smoking in pregnancy and autism spectrum disorder (autism) overall. To address remaining questions about the unexplained heterogeneity between study results and the possibility of risk for specific autism sub-phenotypes, we conducted a whole-population cohort study in Denmark. We followed births 1991-2011 (1,294,906 persons, including 993,301 siblings in 728,271 families), from 1 year of age until an autism diagnosis (13,547), death, emigration, or December 31, 2012. Autism, with and without attention deficit hyperactivity disorder (ADHD) and with and without intellectual disability (ID) were based on ICD-8 and ICD-10 codes from Danish national health registers, including 3,319 autism + ADHD, 10,228 autism - no ADHD, 2,205 autism + ID, and 11,342 autism - no ID. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) between any maternal smoking (from birth records) and autism (or sub-phenotypes) using survival models with robust standard errors, stratifying by birth year and adjusting for child sex, parity, and parental age, education, income, and psychiatric history. To additionally address confounding using family designs, we constructed a maternal cluster model (adjusting for the smoking proportion within the family), and a stratified sibling model. Associations with maternal smoking and autism were elevated in conventional adjusted analyses (HR of 1.17 [1.13-1.22]) but attenuated in the maternal cluster (0.98 [0.88-1.09]) and sibling (0.86 [0.64-1.15]) models. Similarly, risks of autism sub-phenotypes with maternal smoking were attenuated in the family-based models. Together these results support that smoking in pregnancy is not linked with autism or select autism comorbid sub-phenotypes after accounting for familial confounding. Autism Res 2020, 13: 134-144. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Smoking during pregnancy has many harmful impacts, which may include harming the baby's developing brain. However, in a study of thousands of families in Denmark, it does not appear that smoking in pregnancy leads to autism or autism in combination with intellectual problems or attention deficits, once you account for the way smoking patterns and developmental disabilities run in families.
| S-EPMC7919848 | biostudies-literature
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:BackgroundFindings from previous studies on maternal 25(OH)D levels during pregnancy and offspring schizophrenia are limited and inconsistent.MethodsWe used nationwide population-based register data with a nested case-control design to examine the association between maternal 25(OH)D levels during pregnancy and offspring schizophrenia. The cases of schizophrenia (n = 1145) were born from 1987 to 1997, and received a diagnosis of schizophrenia by 2017, and were matched with equal number of controls. A quantitative immunoassay was used to measure maternal 25(OH)D in archived maternal serum in the national biobank of the Finnish Maternity Cohort, collected during the first and early second trimesters. Conditional logistic regression models examined the association between maternal 25(OH)D levels and offspring schizophrenia.ResultsNo significant association was found between log-transformed maternal 25(OH)D levels and schizophrenia in unadjusted (OR 0.96, 95 % CI 0.78-1.17, p = 0.69) or adjusted analyses (aOR 0.98, 95 % CI 0.79-1.22, p = 0.89). Analyses by quintiles also revealed no association between the lowest quintile of maternal 25(OH)D levels and schizophrenia (OR 1.09, 95 % CI 0.81-1.45, p = 0.55; aOR 1.06, 95 % CI 0.78-1.45, p = 0.71). Maternal 25(OH)D levels, measured in categories, either in deficient category (OR 1.07 (0.85-1.35), p = 0.52; aOR 1.05 (0.81-1.34), p = 0.88) or insufficient category (OR 1.13, 95 % CI 0.92-1.40, p = 0.23; aOR 1.13, 95 % CI 0.90-1.41, p = 0.27) were also not associated with offspring schizophrenia.ConclusionsMaternal vitamin D levels in early pregnancy were not associated with offspring schizophrenia. Future studies measuring vitamin D during different stages of gestation are needed to draw firm conclusions.
| S-EPMC11412259 | biostudies-literature
Project description:BackgroundPrevious studies have attributed high maternal weight gain during pregnancy and pre-pregnancy obesity to a higher risk for autism spectrum disorder (ASD). Maternal underweight was not previously explored with respect to ASD risk.MethodsWe evaluated the association between maternal pre-pregnancy body mass index (BMI) and ASD occurrence among singletons born into the General Practice Research Database from 1993 to 2008. Case subjects were children with a diagnosis of ASD from birth to 2010. Up to four control subjects were matched to each case subject on birth year, sex, and general practice. Restricted cubic splines were used to assess the non-linearity of the association between maternal BMI and ASD. All study subjects were classified as underweight, normal weight, overweight, or obese based on maternal pre-pregnancy BMI using the WHO Classification Standard. Conditional logistic regression was used to calculate unadjusted and multivariable adjusted odds ratios for the association between categorical BMI (reference=normal weight) and the occurrence of ASD.ResultsThe association between maternal BMI and ASD occurrence was non-linear and J-shaped. The adjusted ORs for maternal underweight and obesity were 1.43 (95% CI 1.01, 2.04) and 1.54 (95% CI 1.26, 1.89) respectively.ConclusionsResults suggest that extremes in maternal BMI may be associated with modest increases in the risk for ASD among offspring.
| S-EPMC5849232 | biostudies-literature
Project description:BackgroundTo examine the prospective association between multivitamin supplementation during pregnancy and biomarker measures of maternal plasma folate and vitamin B12 levels at birth and child's Autism Spectrum Disorder (ASD) risk.MethodsThis report included 1257 mother-child pairs, who were recruited at birth and prospectively followed through childhood at the Boston Medical Center. ASD was defined from diagnostic codes in electronic medical records. Maternal multivitamin supplementation was assessed via questionnaire interview; maternal plasma folate and B12 were measured from samples taken 2-3 days after birth.ResultsModerate (3-5 times/week) self-reported supplementation during pregnancy was associated with decreased risk of ASD, consistent with previous findings. Using this as the reference group, low (≤2 times/week) and high (>5 times/week) supplementation was associated with increased risk of ASD. Very high levels of maternal plasma folate at birth (≥60.3 nmol/L) had 2.5 times increased risk of ASD [95% confidence interval (CI) 1.3, 4.6] compared to folate levels in the middle 80th percentile, after adjusting for covariates including MTHFR genotype. Similarly, very high B12 (≥536.8 pmol/L) showed 2.5 times increased risk (95% CI 1.4, 4.5).ConclusionThere was a 'U shaped' relationship between maternal multivitamin supplementation frequency and ASD risk. Extremely high maternal plasma folate and B12 levels at birth were associated with ASD risk. This hypothesis-generating study does not question the importance of consuming adequate folic acid and vitamin B12 during pregnancy; rather, raises new questions about the impact of extremely elevated levels of plasma folate and B12 exposure in-utero on early brain development.
| S-EPMC5796848 | biostudies-literature