Publications by authors named "M Daniele Fallin"

205 Publications

Maternal Psychiatric Conditions, Treatment With Selective Serotonin Reuptake Inhibitors, and Neurodevelopmental Disorders.

Biol Psychiatry 2021 Apr 14. Epub 2021 Apr 14.

Division of Research, Kaiser Permanente Northern California, Oakland, California.

Background: This study aims to clarify relationships of maternal psychiatric conditions and selective serotonin reuptake inhibitor (SSRI) use during preconception and pregnancy with risk of neurodevelopmental disorders in offspring.

Methods: We used data from the Study to Explore Early Development, a multisite case-control study conducted in the United States among children born between 2003 and 2011. Final study group classifications of autism spectrum disorder (ASD) (n = 1367), developmental delays or disorders (DDs) (n = 1750), and general population controls (n = 1671) were determined by an in-person standardized developmental assessment. Maternal psychiatric conditions and SSRI use during pregnancy were ascertained from both self-report and medical records. We used logistic regression to evaluate associations of ASD and DDs (vs. population controls) with maternal psychiatric conditions and SSRI treatment in pregnancy. To reduce confounding by indication, we also examined SSRI associations in analyses restricted to mothers with psychiatric conditions during pregnancy.

Results: Psychiatric conditions and SSRI use during pregnancy were significantly more common among mothers of children with either ASD or DDs than among population controls. Odds of ASD were similarly elevated among mothers with psychiatric conditions who did not use SSRIs during pregnancy (adjusted odds ratio 1.81, 95% confidence interval 1.44-2.27) as in mothers who did use SSRIs (adjusted odds ratio 2.05, 95% confidence interval 1.50-2.80). Among mothers with psychiatric conditions, SSRI use was not significantly associated with ASD in offspring (adjusted odds ratio 1.14, 95% confidence interval 0.80-1.62). Primary findings for DDs exhibited similar relationships to those observed with ASD.

Conclusions: Maternal psychiatric conditions but not use of SSRIs during pregnancy were associated with increased risk of neurodevelopmental disorders in offspring.
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http://dx.doi.org/10.1016/j.biopsych.2021.04.002DOI Listing
April 2021

The Association of Prenatal Vitamins and Folic Acid Supplement Intake with Odds of Autism Spectrum Disorder in a High-Risk Sibling Cohort, the Early Autism Risk Longitudinal Investigation (EARLI).

J Autism Dev Disord 2021 Jun 10. Epub 2021 Jun 10.

Department of Public Health Sciences and The MIND Institute, School of Medicine, University of California-Davis, UC Davis School of Medicine - Medical Sciences 1C, Suite 123, Davis, CA, 95616, USA.

We examined maternal prenatal vitamin use or supplemental folic acid intake during month one of pregnancy for association with autism spectrum disorder (ASD) in the Early Autism Risk Longitudinal Investigation, an enriched-risk pregnancy cohort. Total folic acid intake was calculated from monthly prenatal vitamins, multivitamins, and other supplement reports. Clinical assessments through age 3 years classified children as ASD (n = 38) or non-ASD (n = 153). In pregnancy month one, prenatal vitamin use (59.7%) was not significantly associated with odds of ASD (OR = 0.70, 95%CI 0.32, 1.53). Sample size was limited and residual confounding was possible. Given the estimated effect sizes in this and previous work, prenatal vitamin intake during early pregnancy could be a clinically useful preventative measure for ASD.
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http://dx.doi.org/10.1007/s10803-021-05110-9DOI Listing
June 2021

Health Status and Health Care Use Among Adolescents Identified With and Without Autism in Early Childhood - Four U.S. Sites, 2018-2020.

MMWR Morb Mortal Wkly Rep 2021 Apr 30;70(17):605-611. Epub 2021 Apr 30.

Persons identified in early childhood as having autism spectrum disorder (autism) often have co-occurring health problems that extend into adolescence (1-3). Although only limited data exist on their health and use of health care services as they transition to adolescence, emerging data suggest that a minority of these persons receive recommended guidance* from their primary care providers (PCPs) starting at age 12 years to ensure a planned transition from pediatric to adult health care (4,5). To address this gap in data, researchers analyzed preliminary data from a follow-up survey of parents and guardians of adolescents aged 12-16 years who previously participated in the Study to Explore Early Development (https://www.cdc.gov/ncbddd/autism/seed.html). The adolescents were originally studied at ages 2-5 years and identified at that age as having autism (autism group) or as general population controls (control group). Adjusted prevalence ratios (aPRs) that accounted for differences in demographic characteristics were used to compare outcomes between groups. Adolescents in the autism group were more likely than were those in the control group to have physical difficulties (21.2% versus 1.6%; aPR = 11.6; 95% confidence interval [CI] = 4.2-31.9), and to have additional mental health or other conditions (one or more condition: 63.0% versus 28.9%; aPR = 1.9; 95% CI = 1.5-2.5). Adolescents in the autism group were more likely to receive mental health services (41.8% versus 22.1%; aPR = 1.8, 95% CI = 1.3-2.6) but were also more likely to have an unmet medical or mental health service need (11.0% versus 3.2%; aPR = 3.1; 95% CI = 1.1-8.8). In both groups, a small percentage of adolescents (autism, 7.5%; control, 14.1%) received recommended health care transition (transition) guidance. These findings are consistent with previous research (4,5) indicating that few adolescents receive the recommended transition guidance and suggest that adolescents identified with autism in early childhood are more likely than adolescents in the general population to have unmet health care service needs. Improved provider training on the heath care needs of adolescents with autism and coordination of comprehensive programs to meet their needs can improve delivery of services and adherence to recommended guidance for transitioning from pediatric to adult health care.
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http://dx.doi.org/10.15585/mmwr.mm7017a1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084123PMC
April 2021

Maternal blood metal concentrations and whole blood DNA methylation during pregnancy in the Early Autism Risk Longitudinal Investigation (EARLI).

Epigenetics 2021 Apr 2:1-16. Epub 2021 Apr 2.

Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins University, Baltimore, USA.

The maternal epigenome may be responsive to prenatal metals exposures. We tested whether metals are associated with concurrent differential maternal whole blood DNA methylation. In the Early Autism Risk Longitudinal Investigation cohort, we measured first or second trimester maternal blood metals concentrations (cadmium, lead, mercury, manganese, and selenium) using inductively coupled plasma mass spectrometry. DNA methylation in maternal whole blood was measured on the Illumina 450 K array. A subset sample of 97 women had both measures available for analysis, all of whom did not report smoking during pregnancy. Linear regression was used to test for site-specific associations between individual metals and DNA methylation, adjusting for cell type composition and confounding variables. Discovery gene ontology analysis was conducted on the top 1,000 sites associated with each metal. We observed hypermethylation at 11 DNA methylation sites associated with lead (FDR False Discovery Rate -value <0.1), near the genes , and . Lead-associated sites were enriched (FDR -value <0.1) for the pathways cell adhesion, nervous system development, and calcium ion binding. Manganese was associated with hypermethylation at four DNA methylation sites (FDR -value <0.1), one of which was near the gene . Manganese-associated sites were enriched for cellular metabolism pathways (FDR -value<0.1). Effect estimates for DNA methylation sites associated ( < 0.05) with cadmium, lead, and manganese were highly correlated (Pearson ρ > 0.86). DNA methylation sites associated with lead and manganese may be potential biomarkers of exposure or implicate downstream gene pathways.
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http://dx.doi.org/10.1080/15592294.2021.1897059DOI Listing
April 2021

DNA methylation and cancer incidence: lymphatic-hematopoietic versus solid cancers in the Strong Heart Study.

Clin Epigenetics 2021 Feb 25;13(1):43. Epub 2021 Feb 25.

Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA.

Background: Epigenetic alterations may contribute to early detection of cancer. We evaluated the association of blood DNA methylation with lymphatic-hematopoietic cancers and, for comparison, with solid cancers. We also evaluated the predictive ability of DNA methylation for lymphatic-hematopoietic cancers.

Methods: Blood DNA methylation was measured using the Illumina Infinium methylationEPIC array in 2324 Strong Heart Study participants (41.4% men, mean age 56 years). 788,368 CpG sites were available for differential DNA methylation analysis for lymphatic-hematopoietic, solid and overall cancers using elastic-net and Cox regression models. We conducted replication in an independent population: the Framingham Heart Study. We also analyzed differential variability and conducted bioinformatic analyses to assess for potential biological mechanisms.

Results: Over a follow-up of up to 28 years (mean 15), we identified 41 lymphatic-hematopoietic and 394 solid cancer cases. A total of 126 CpGs for lymphatic-hematopoietic cancers, 396 for solid cancers, and 414 for overall cancers were selected as predictors by the elastic-net model. For lymphatic-hematopoietic cancers, the predictive ability (C index) increased from 0.58 to 0.87 when adding these 126 CpGs to the risk factor model in the discovery set. The association was replicated with hazard ratios in the same direction in 28 CpGs in the Framingham Heart Study. When considering the association of variability, rather than mean differences, we found 432 differentially variable regions for lymphatic-hematopoietic cancers.

Conclusions: This study suggests that differential methylation and differential variability in blood DNA methylation are associated with lymphatic-hematopoietic cancer risk. DNA methylation data may contribute to early detection of lymphatic-hematopoietic cancers.
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http://dx.doi.org/10.1186/s13148-021-01030-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908806PMC
February 2021