Vitamin D levels of pregnant immigrant women and developmental disorders of language, learning and coordination in offspring.

BACKGROUND: Prenatal vitamin D deficiency is a common health concern among immigrants. No previous studies have examined the associations between prenatal vitamin D levels and developmental disorders of language, scholastic skills, and coordination in an immigrant sample. METHODS: The sample included 542 immigrant mothers of cases with language, scholastic, coordination or mixed developmental disorders, 443 immigrant mothers of controls without these disorders and 542 Finnish mothers of controls. Maternal vitamin D was measured in serum samples collected during early pregnancy and stored in a national biobank. RESULTS: The mean vitamin D levels during pregnancy were 25.0 (SD 14.4) nmol/L for immigrant mothers of cases, 25.4 (SD 15.5) for immigrant mothers of controls and 42.3 (SD 19.1) for Finnish mothers of controls. Low maternal vitamin D levels during pregnancy were not associated with the selected developmental disorders in offspring when immigrant mothers of cases were compared to immigrant mothers of controls (adjusted OR for continuous log-transformed vitamin D: 1.01, 95% CI 0.75-1.36, p = 0.96). When immigrant mothers of cases were compared to Finnish mothers of controls, the adjusted OR for continuous vitamin D was 18.94 (95% CI 11.47-31.25), p <0.001). The results were similar when vitamin D was examined as a categorical variable or divided into quintiles. CONCLUSIONS: Prenatal vitamin D levels were low, and similar, among immigrant mothers of cases with selected developmental disorders and unaffected controls. This indicates that vitamin D unlikely mediates previously observed associations between maternal immigrant status and the selected developmental disorders in offspring. The proportion of immigrant mothers with severe vitamin D deficiency was very high, which underlines the importance of prenatal counselling and overall public health efforts to improve immigrant health.

Maternal Vitamin D Levels during Pregnancy and Offspring Psychiatric Outcomes: A Systematic Review.

Prenatal exposure to vitamin D may play a significant role in human brain development and function. Previous epidemiological studies investigating the associations between maternal vitamin D status and offspring developmental and psychiatric outcomes in humans have been inconclusive. We aimed to systematically assess the results of previously published studies that examined the associations between maternal vitamin D levels, measured as circulating 25(OH)D levels in pregnancy or at birth, and offspring neuropsychiatric and psychiatric outcomes. Systematic searches were conducted using MEDLINE, Embase, PsychINFO and Web of Science for studies published by 10 August 2022. We included human observational studies that examined associations between prenatal or perinatal vitamin D levels and offspring neuropsychiatric and psychiatric outcomes and were published in English in peer-reviewed journals. Of the 3729 studies identified, 66 studies were screened for full texts and 29 studies published between 2003 and 2022 were included in the final review. There was a small amount of evidence for the association between prenatal vitamin D deficiency and autism spectrum disorder. When studies with larger sample sizes and stricter definitions of vitamin D deficiency were considered, positive associations were also found for attention-deficit/hyperactivity disorder and schizophrenia. Future studies with larger sample sizes, longer follow-up periods and prenatal vitamin D assessed at multiple time points are needed.

Prenatal Vitamin D Levels in Maternal Sera and Offspring Specific Learning Disorders.

Recent evidence has suggested potential harmful effects of vitamin D deficiency during pregnancy on offspring brain development, for example, elevated risks for neuropsychiatric disorders. Findings on general cognition and academic achievement are mixed, and no studies have examined the effect of prenatal 25-hydroxyvitamin D (25(OH)D) levels on diagnosed specific learning disorders, which was the aim of this study. We examined a nested case-control sample from the source cohort of all singleton-born children in Finland between 1996 and 1997 (n = 115,730). A total of 1607 cases with specific learning disorders (mean age at diagnosis: 9.9 years) and 1607 matched controls were identified from Finnish nationwide registers. Maternal 25(OH)D levels were analyzed from serum samples collected during the first trimester of pregnancy and stored in a national biobank. Conditional logistic regression was used to test the association between maternal 25(OH)D and offspring specific learning disorders. There were no significant associations between maternal 25(OH)D levels and specific learning disorders when vitamin D was examined as a log-transformed continuous variable (adjusted OR 0.98, 95% CI 0.82-1.18, p = 0.84) or as a categorical variable (25(OH)D < 30 nmol/L: adjusted OR 1.03, 95% CI 0.83-1.28, p = 0.77 compared to levels of >50 nmol/L), nor when it was divided into quintiles (adjusted OR for the lowest quintile 1.00, 95% CI 0.78-1.28, p = 0.99 compared to the highest quintile). This study found no association between low maternal 25(OH)D in early pregnancy and offspring specific learning disorders.

Familial confounding affected the associations between maternal smoking during pregnancy and offspring speech and language, scholastic and coordination disorders.

AIM: This study examined the associations between prenatal smoking and speech and language, scholastic, coordination and mixed developmental disorders in offspring, using sibling and population controls. METHODS: National Finnish registers were used to identify all 690 654 singletons born between 1996 and 2007 and any cases diagnosed with speech and language, scholastic, coordination and mixed developmental disorders by the end of 2012. Cases were compared to population controls, biological full-siblings and maternal half-siblings born during the same period. Conditional logistic regression was used to assess any associations between smoking during pregnancy and the selected developmental disorders. RESULTS: Prenatal smoking was higher in the mothers of the 27 297 cases (21.7%) than the 99 876 population controls (14.5%). The adjusted odds ratio for smoking throughout pregnancy, and any diagnosis of speech and language, scholastic, coordination or mixed developmental disorders, was 1.29 (95% confidence interval 1.24-1.34). However, when we compared a subsample of 15 406 cases and their 20 657 siblings, the association was no longer statistically significant (odds ratio 1.09, 95% confidence interval 0.98-1.21). CONCLUSION: The sibling comparisons suggested that the associations between prenatal smoking and speech and language, scholastic, coordination and mixed developmental disorders were confounded by familial factors shared by differentially exposed siblings.

Relative age and specific learning disorder diagnoses: A Finnish population-based cohort study.

Background: Being among the youngest in class has previously been associated with attention-deficit/hyperactivity disorder (ADHD) and academic disadvantage, but the relative age effect on learning disorders is less well understood. This study examined whether relatively young children are more likely to be diagnosed with specific learning disorders than their older peers. Methods: The setting included all 388,650 children born singleton in Finland from 1996 to 2002. Cases diagnosed with specific learning disorders in specialized health care by the age of 10 were identified from national registers. Cumulative incidences of specific learning disorders and the corresponding incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for each birth month compared to January. Results: During follow-up, 3162 (0.8% of 388,650) children were diagnosed with a specific learning disorder. Children born in December displayed higher cumulative incidences for specific learning disorders than children born in January (IRR: 1.77, 95% CI: 1.50-2.11). The findings were similar for girls (IRR: 2.01, 1.44-2.83) and boys (IRR: 1.70, 1.39-2.08). ADHD did not explain the association, as the IRR for the youngest children with specific learning disorders and ADHD was 1.59 (1.13-2.26) compared to those without ADHD (IRR: 1.84, 1.51-2.24). Conclusions: Relatively younger children in Finnish schools were more likely to be diagnosed with a specific learning disorder by the age of 10. Increased awareness of how relative age differences affect the likelihood for children to be diagnosed with specific learning disorders is needed among parents, clinicians, and teachers.

Social risk factors for speech, scholastic and coordination disorders: a nationwide register-based study.

BACKGROUND: Broadly defined learning and coordination disorders (LCDs) are common in the population and have previously been associated with familial social risk factors and male sex. However, comprehensive nationwide studies of these risk factors in LCD subgroups are lacking. Our objective was to assess different LCDs in relation to sex and maternal education, marital status and socioeconomic status based on occupation. METHODS: We conducted a nationwide register-based study. The following diagnoses were identified from the Finnish Hospital Discharge Register (FHDR) according to the ICD-10 (n = 28,192): speech disorders (F80), scholastic disorders (F81), motor and coordination disorders (F82) and mixed developmental disorder (F83). To study cumulative incidence and male: female ratios of service use of LCDs, we used a cohort design among all Finnish children born singleton 1996-2007 (n = 690,654); to study social risk factors, we used a nested case-control design with extensive register data on both cases and matched controls (n = 106,616). RESULTS: The cumulative incidence was 4.7% for any LCD by age 15 and the changes in cumulative incidence over time were minor. The male: female ratios were 2.2-3.0 across LCD subgroups. Learning and coordination disorders were more common in households with lower maternal education, socioeconomic status based on occupation and among children with single mothers at the time of birth; the odds ratios (OR) for any LCD were 1.2-1.9 across risk factors. The odds for LCD diagnosis increased linearly with the number of social risk factors, except for coordination disorder. The effect size of three risk factors was highest in the group with mixed or multiple LCDs; OR 3.76 (95% CI 3.31-4.28). CONCLUSIONS: Multiple social risk factors increase the odds for multiple, more comprehensive learning difficulties. The findings have implications for service planning, as early identification and interventions of learning and coordination disorders might reduce related long-term social adversities.

Intravenous epinephrine infusion test in diagnosis of catecholaminergic polymorphic ventricular tachycardia.

INTRODUCTION: A test involving intravenous infusion of epinephrine has been proposed as a method alternative to exercise stress test in diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT). We aimed at estimating the predictive value of intravenous epinephrine administration in CPVT patients with frequent exercise-induced ventricular ectopy. METHODS AND RESULTS: We recruited 81 subjects, including 25 CPVT-linked ryanodine receptor 2 (RYR2) mutation carriers, 11 genetically undefined CPVT patients, and 45 unaffected family members. All subjects underwent a maximal exercise stress test and an intravenous epinephrine infusion test. Exercise stress test was positive in 25 (31%) patients including 14 of 25 (56%) established RYR2-mutation carriers and all 11 (100%) genetically undefined CPVT patients. Epinephrine infusion induced arrhythmias in 3 (12%) RYR2-mutation carriers, 4 (36%) genetically undefined CPVT patients, and 1 (2%) unaffected family member. A total of 18 exercise stress test positive patients did not respond to intravenous epinephrine administration, whereas only 1 epinephrine test responder had a normal exercise stress test. Thus, if exercise stress test is used as a standard, the sensitivity of the epinephrine infusion test is 28% and specificity is 98%. CONCLUSIONS: Intravenous epinephrine infusion has low sensitivity and may not be considered as an alternative method for a maximal exercise stress test in diagnosis of CPVT.