Dataset Information

Association of Maternal Neurodevelopmental Risk Alleles With Early-Life Exposures.

ABSTRACT:

Importance

Early-life exposures, such as prenatal maternal lifestyle, illnesses, nutritional deficiencies, toxin levels, and adverse birth events, have long been considered potential risk factors for neurodevelopmental disorders in offspring. However, maternal genetic factors could be confounding the association between early-life exposures and neurodevelopmental outcomes in offspring, which makes inferring a causal relationship problematic.

Objective

To test whether maternal polygenic risk scores (PRSs) for neurodevelopmental disorders were associated with early-life exposures previously linked to the disorders.

Design, setting, and participants

In this UK population-based cohort study, 7921 mothers with genotype data from the Avon Longitudinal Study of Parents and Children (ALSPAC) underwent testing for association of maternal PRS for attention-deficit/hyperactivity disorder (ADHD PRS), autism spectrum disorder (ASD PRS), and schizophrenia (SCZ PRS) with 32 early-life exposures. ALSPAC data collection began September 6, 1990, and is ongoing. Data were analyzed for the current study from April 1 to September 1, 2018.

Exposures

Maternal ADHD PRS, ASD PRS, and SCZ PRS were calculated using discovery effect size estimates from the largest available genome-wide association study and a significance threshold of P?Main outcomes and measuresOutcomes measured included questionnaire data on maternal lifestyle and behavior (eg, smoking, alcohol consumption, body mass index, and maternal age), maternal use of nutritional supplements and medications in pregnancy (eg, acetaminophen, iron, zinc, folic acid, and vitamins), maternal illnesses (eg, diabetes, hypertension, rheumatism, psoriasis, and depression), and perinatal factors (eg, birth weight, preterm birth, and cesarean delivery).

Results

Maternal PRSs were available from 7921 mothers (mean [SD] age, 28.5?[4.8] years). The ADHD PRS was associated with multiple prenatal factors, including infections (odds ratio [OR], 1.11; 95% CI, 1.04-1.18), use of acetaminophen during late pregnancy (OR, 1.11; 95% CI, 1.04-1.18), lower blood levels of mercury (? coefficient, -0.06; 95% CI, -0.11 to -0.02), and higher blood levels of cadmium (? coefficient, 0.07; 95% CI, 0.05-0.09). Little evidence of associations between ASD PRS or SCZ PRS and prenatal factors or of association between any of the PRSs and adverse birth events was found. Sensitivity analyses revealed consistent results.

Conclusions and relevance

These findings suggest that maternal risk alleles for neurodevelopmental disorders, primarily ADHD, are associated with some pregnancy-related exposures. These findings highlight the need to carefully account for potential genetic confounding and triangulate evidence from different approaches when assessing the effects of prenatal exposures on neurodevelopmental disorders in offspring.

SUBMITTER: Leppert B

PROVIDER: S-EPMC6495368 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Maternal Neurodevelopmental Risk Alleles With Early-Life Exposures.

Leppert Beate B Havdahl Alexandra A Riglin Lucy L Jones Hannah J HJ Zheng Jie J Davey Smith George G Tilling Kate K Thapar Anita A Reichborn-Kjennerud Ted T Stergiakouli Evie E

JAMA psychiatry 20190801 8

<h4>Importance</h4>Early-life exposures, such as prenatal maternal lifestyle, illnesses, nutritional deficiencies, toxin levels, and adverse birth events, have long been considered potential risk factors for neurodevelopmental disorders in offspring. However, maternal genetic factors could be confounding the association between early-life exposures and neurodevelopmental outcomes in offspring, which makes inferring a causal relationship problematic.<h4>Objective</h4>To test whether maternal poly ...[more]

PMID: 31042271

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Project description:ImportanceAdverse childhood experiences (ACEs) have been associated with poor mental and physical health outcomes. However, the mechanism of this effect, critical to enhancing public health, remains poorly understood.ObjectiveTo investigate the neurodevelopmental trajectory of the association between early ACEs and adolescent general and emotional health outcomes.Design, setting, and participantsA prospective longitudinal study that began when patients were aged 3 to 6 years who underwent neuroimaging later at ages 7 to 12 years and whose mental and physical health outcomes were observed at ages 9 to 15 years. Sequential mediation models were used to investigate associations between early ACEs and brain structure, emotion development, and health outcomes longitudinally. Children were recruited from an academic medical center research unit.ExposureEarly life adversity.Main outcomes and measuresEarly ACEs in children aged 3 to 7 years; volume of a subregion of the prefrontal cortex, the inferior frontal gyrus, in children aged 6 to 12 years; and emotional awareness, depression severity, and general health outcomes in children and adolescents aged 9 to 15 years.ResultsThe mean (SD) age of 119 patients was 9.65 (1.31) years at the time of scan. The mean (SD) ACE score was 5.44 (3.46). The mean (SD) depression severity scores were 2.61 (1.78) at preschool, 1.77 (1.58) at time 2, and 2.16 (1.64) at time 3. The mean (SD) global physical health scores at time 2 and time 3 were 0.30 (0.38) and 0.33 (0.42), respectively. Sequential mediation in the association between high early ACEs and emotional and physical health outcomes were found. Smaller inferior frontal gyrus volumes and poor emotional awareness sequentially mediated the association between early ACEs and poor general health (model parameter estimate = 0.002; 95% CI, 0.0002-0.056) and higher depression severity (model parameter estimate = 0.007; 95% CI, 0.001-0.021) in adolescence. An increase from 0 to 3 early ACEs was associated with 15% and 25% increases in depression severity and physical health problems, respectively.Conclusions and relevanceStudy findings highlight 1 putative neurodevelopmental mechanism by which the association between early ACEs and later poor mental and physical health outcomes may operate. This identified risk trajectory may be useful to target preventive interventions.

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Dataset Information

Association of Maternal Neurodevelopmental Risk Alleles With Early-Life Exposures.

Importance

Objective

Design, setting, and participants

Exposures

Results

Conclusions and relevance

Publications

Association of Maternal Neurodevelopmental Risk Alleles With Early-Life Exposures.

Similar Datasets

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