Dataset Information

School performance in Danish children exposed to maternal type 1 diabetes in utero: A nationwide retrospective cohort study.

ABSTRACT:

Background

Conflicting results have been reported concerning possible adverse effects on the cognitive function of offspring of mothers with type 1 diabetes (O-mT1D). Previous studies have included offspring of parents from the background population (O-BP), but not offspring of fathers with type 1 diabetes (O-fT1D) as the unexposed reference group.

Methods and findings

This is a population-based retrospective cohort study from 2010 to 2016. Nationally standardized school test scores (range, 1 to 100) were obtained for public school grades 2, 3, 4, 6, and 8 in O-mT1D and compared with those in O-fT1D and O-BP. Of the 622,073 included children, 2,144 were O-mT1D, and 3,474 were O-fT1D. Multiple linear regression models were used to compare outcomes, including the covariates offspring with type 1 diabetes, parity, number of siblings, offspring sex, smoking during pregnancy, parental age, and socioeconomic factors. Mean test scores were 54.2 (standard deviation, SD 24.8) in O-mT1D, 54.4 (SD 24.8) in O-fT1D, and 56.4 (SD 24.7) in O-BP. In adjusted analyses, the mean differences in test scores were -1.59 (95% CI -2.48 to -0.71, p < 0.001) between O-mT1D and O-BP and -0.78 (95% CI -1.48 to -0.08, p = 0.03) between O-fT1D and O-BP. No significant difference in the adjusted mean test scores was found between O-mT1D and O-fT1D (p = 0.16). The study's limitation was no access to measures of glycemic control during pregnancy.

Conclusions

O-mT1D achieved lower test scores than O-BP but similar test scores compared with O-fT1D. Glycemic control during pregnancy is essential to prevent various adverse pregnancy outcomes in women with type 1 diabetes. However, the present study reduces previous concerns regarding adverse effects of in utero hyperglycemia on offspring cognitive function.

SUBMITTER: Spangmose AL

PROVIDER: S-EPMC9041831 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

School performance in Danish children exposed to maternal type 1 diabetes in utero: A nationwide retrospective cohort study.

Spangmose Anne Lærke AL Skipper Niels N Knorr Sine S Wullum Gundersen Tina T Beck Jensen Rikke R Damm Peter P Lykke Mortensen Erik E Pinborg Anja A Svensson Jannet J Clausen Tine T

PLoS medicine 20220426 4

<h4>Background</h4>Conflicting results have been reported concerning possible adverse effects on the cognitive function of offspring of mothers with type 1 diabetes (O-mT1D). Previous studies have included offspring of parents from the background population (O-BP), but not offspring of fathers with type 1 diabetes (O-fT1D) as the unexposed reference group.<h4>Methods and findings</h4>This is a population-based retrospective cohort study from 2010 to 2016. Nationally standardized school test scor ...[more]

PMID: 35472047

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Project description:Aims/hypothesisIndividuals exposed to maternal diabetes in utero are more likely to develop metabolic and cardiovascular diseases later in life. This may be partially attributable to epigenetic regulation of gene expression. We performed an epigenome-wide association study to examine whether differential DNA methylation, a major source of epigenetic regulation, can be observed in offspring of mothers with type 2 diabetes during the pregnancy (OMD) compared with offspring of mothers with no diabetes during the pregnancy (OMND).MethodsDNA methylation was measured in peripheral blood using the Illumina HumanMethylation450K BeadChip. A total of 423,311 CpG sites were analysed in 388 Pima Indian individuals, mean age at examination was 13.0 years, 187 of whom were OMD and 201 were OMND. Differences in methylation between OMD and OMND were assessed.ResultsForty-eight differentially methylated CpG sites (with an empirical false discovery rate ≤0.05), mapping to 29 genes and ten intergenic regions, were identified. The gene with the strongest evidence was LHX3, in which six CpG sites were hypermethylated in OMD compared with OMND (p ≤ 1.1 × 10-5). Similarly, a CpG near PRDM16 was hypermethylated in OMD (1.1% higher, p = 5.6 × 10-7), where hypermethylation also predicted future diabetes risk (HR 2.12 per SD methylation increase, p = 9.7 × 10-5). Hypermethylation near AK3 and hypomethylation at PCDHGA4 and STC1 were associated with exposure to diabetes in utero (AK3: 2.5% higher, p = 7.8 × 10-6; PCDHGA4: 2.8% lower, p = 3.0 × 10-5; STC1: 2.9% lower, p = 1.6 × 10-5) and decreased insulin secretory function among offspring with normal glucose tolerance (AK3: 0.088 SD lower per SD of methylation increase, p = 0.02; PCDHGA4: 0.08 lower SD per SD of methylation decrease, p = 0.03; STC1: 0.072 SD lower per SD of methylation decrease, p = 0.05). Seventeen CpG sites were also associated with BMI (p ≤ 0.05). Pathway analysis of the genes with at least one differentially methylated CpG (p < 0.005) showed enrichment for three relevant biological pathways.Conclusions/interpretationIntrauterine exposure to diabetes can affect methylation at multiple genomic sites. Methylation status at some of these sites can impair insulin secretion, increase body weight and increase risk of type 2 diabetes.

Project description:ImportanceConcerns exist about long-term neurodevelopmental consequences of prenatal exposure to antidepressants.ObjectiveTo evaluate whether maternal prescription fill for antidepressants in pregnancy was associated with performance in standardized tests among Danish schoolchildren.Design, setting, and participantsPopulation-based retrospective cohort study of children born in Denmark between January 1, 1997, and December 31, 2009, attending public primary and lower secondary school. The children included had completed a language or mathematics test as part of the Danish National Test Program between January 1, 2010, and December 31, 2018. The age range of the eligible schoolchildren was 7 to 17 years.ExposuresMaternal prescription fill for antidepressants during pregnancy, obtained from the Danish Prescription Register.Main outcomes and measuresThe difference in standardized scores between children with and without maternal prescription fill for antidepressants in mathematics and language tests (scale, 1-100; higher scores indicate better test results) was estimated using linear regression models, adjusted for relevant confounders. Ten sensitivity analyses were performed, including a sibling-controlled analysis.ResultsAmong the 575 369 children included (51.1% males), 10 198 (1.8%) were born to mothers filling an antidepressant prescription during pregnancy. The mean (SD) age of children at the time of testing spanned from 8.9 (0.4) years in grade 2 to 14.9 (0.4) years in grade 8. Maternal prescription fill for antidepressants was significantly associated with a poorer performance in mathematics (mean test scores for the group exposed to maternal antidepressant fill: 52.1 [95% CI, 51.7-52.6] and for the group not exposed to maternal antidepressant fill: 57.4 [95% CI, 57.3-57.4]; adjusted difference, -2.2 [95% CI, -2.7 to -1.6]), but not in language (mean test scores for the exposed group: 53.4 [95% CI, 53.1-53.7] and for the not exposed group: 56.6 [95% CI, 56.5-56.6]; adjusted difference, -0.1 [95% CI, -0.6 to 0.3]). In the sibling-controlled analysis, the adjusted difference in mathematics (mean scores for the exposed group: 53.5 [95% CI, 52.7-54.3] and for the not exposed group: 59.0 [95% CI, 58.9-59.1]) was -2.8 (95% CI, -4.5 to -1.2) and in language (mean test scores for the exposed group: 53.9 [95% CI, 53.2-54.6] and for the not exposed group: 56.6 [95% CI, 56.5-56.7]) was -0.3 (95% CI, -1.9 to 1.2).Conclusions and relevanceIn this study of public schoolchildren in Denmark, children whose mothers had filled prescriptions for antidepressants during pregnancy, compared with children whose mothers did not fill prescriptions for antidepressants during pregnancy, had a 2-point lower standardized test score in mathematics, a difference that was statistically significant, but had no significant difference in language test scores. The magnitude of the difference in the mathematics test score was small and of uncertain clinical importance, and the findings must be weighed against the benefits of treating maternal depression during pregnancy.

Dataset Information

School performance in Danish children exposed to maternal type 1 diabetes in utero: A nationwide retrospective cohort study.

Background

Methods and findings

Conclusions

Publications

School performance in Danish children exposed to maternal type 1 diabetes in utero: A nationwide retrospective cohort study.

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