Vitamin D status in pregnancy and cord blood is associated with symptoms of attention-deficit hyperactivity disorder at age 5 years: Results from Odense Child Cohort.

BACKGROUND: Vitamin D status in pregnancy may affect offspring neurodevelopment. OBJECTIVE: The objective was to investigate the association between serum 25-hydroxyvitamin D in cord blood and pregnancy and symptoms of attention-deficit hyperactivity disorder in 5-year-old offspring. METHOD: In Odense Child Cohort, Denmark, 944 mother-child pairs had data on pregnancy or cord serum 25-hydroxyvitamin D and parent-rated attention-deficit hyperactivity disorder symptom score by Child Behavior Checklist for ages 1.5-5 years. Adjusted multiple linear regression and two-stage exposure analyses were performed for serum 25-hydroxyvitamin D associations to the attention-deficit hyperactivity disorder symptom score. RESULTS: The mean (standard deviation) serum 25-hydroxyvitamin D in cord blood was 48.0 (21.8) nmol/L; early pregnancy was 65.5 (20.2) nmol/L and late pregnancy was 79.3 (25.7) nmol/L. The median (interquartile range) age of child at examination was 5.2 (5.1-5.4) years and median (interquartile range) attention-deficit hyperactivity disorder symptom score was 2 (0-3) points. In adjusted analyses, serum 25-hydroxyvitamin D of <25 nmol/L and <32 nmol/L in cord blood and <25 nmol/L in early pregnancy was associated with 0.9 [95% confidence interval: 0.4, 1.3], 0.5 [0.1, 0.9] and 2.1 [0.8, 3.4] points higher attention-deficit hyperactivity disorder symptom score vs reference. In the two-stage exposure analysis, attention-deficit hyperactivity disorder symptom score decreased by 0.4 points per 25 nmol/L increase in serum 25-hydroxyvitamin D. Moreover, serum 25-hydroxyvitamin D of <25 nmol/L in early pregnancy and cord was associated with a five-fold and a two-fold risk of attention-deficit hyperactivity disorder symptom score ⩾90th percentile, adjusted odds ratio [95% confidence interval] = 4.9 [1.3, 19.0] and 2.2 [1.2, 3.9]. CONCLUSION: In this cohort, serum 25-hydroxyvitamin D <25 nmol/L in cord blood and early pregnancy were risk factors for higher attention-deficit hyperactivity disorder symptom score in 5-year-old children, suggesting a protective effect of vitamin D on attention-deficit hyperactivity disorder traits at preschool age.

Prenatal and early postnatal exposure to perfluoroalkyl substances and bone mineral content and density in the Odense Child Cohort.

INTRODUCTION: Exposure to perfluoroalkyl substances (PFAS) has been associated with lower bone mineral density (BMD) in animal and human studies, but prospective data from children are limited. OBJECTIVES: To determine associations between prenatal and early postnatal PFAS exposure and BMD at age 7 years. METHODS: In the Odense Child Cohort, Denmark, pregnant women were recruited in 2010-2012, and their children were invited for subsequent health examinations. At 12 weeks of gestation the pregnant women delivered a serum sample, and at age 18 months serum was obtained from the child to measure perfluorooctane sulfonic acid(PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) by LC-MS/MS. At age 7 years DXA scans were performed to measure bone mineral content (BMC) and BMD Z-score. PFAS in pregnancy (n = 881) and/or at age 18 months (n = 668) were regressed against DXA measurements, adjusted for maternal education, child height Z-score, sex (for BMC) and for postnatal exposure, additionally duration of total breastfeeding. We additionally performed structural equation models determining combined effects of pre-and postnatal PFAS exposures. RESULTS: Higher prenatal and early postnatal serum concentrations of all measured PFAS were associated with lower BMC and BMD Z-scores at age 7 years, all estimates were negative although not all significant. For each doubling of 18-month exposure to PFNA or PFOS, BMD Z-scores were lowered by -0.10 (95 % CI -0.19;-0.00) and -0.08 (-0.17;-0.00), respectively after adjustment. Pre- and postnatal PFAS were correlated, but structural equation models suggested that associations with BMD were stronger for 18-month than prenatal PFAS exposure. DISCUSSION: Bone density is established in childhood, and a reduction in BMD during early childhood may have long-term implication for peak bone mass and lifelong bone health. Future studies of the impact of PFAS exposure on fracture incidence will help elucidate the clinical relevance.

Vitamin D status in pregnancy and childhood associates with intelligence quotient at age 7 years: An Odense child cohort study.

OBJECTIVES: Animal studies indicate a key role for vitamin D in brain development and function, but observational studies in humans only suggests a borderline positive association between prenatal vitamin D exposure and cognitive development in the offspring. Knowledge gaps include insights in exposure time window and differences by sex for the association. We aimed to investigate the association between blood concentrations of serum 25-hydroxyvitamin D measured at four different time points and intelligence quotient score at the age of 7 years, including analyses spilt by child sex. METHODS: In Odense child cohort, we included 1404 mother-child pairs with serum 25-hydroxyvitamin D data from early pregnancy to age 7 years. Full-scale intelligence quotient was assessed with Wechsler Intelligence Scale for Children - fifth edition. Associations were adjusted for maternal education, pre-pregnancy body mass index, gestational age, sex and head circumference. Subanalyses stratified by sex were performed. RESULTS: The median (interquartile range) serum 25-hydroxyvitamin D in cord was 45.88 (31.15-61.08) nmol/L; early pregnancy, 66.45 (51.29-78.74); late pregnancy, 79.13 (59.69-97.31); 7 years, 66.29 (53.45-80.23) nmol/L. The mean (standard deviation) full-scale intelligence quotient was 99.44 (11.98). In adjusted analyses, cord serum 25-hydroxyvitamin D < 50 nmol/L was associated with 2.2 points lower full-scale intelligence quotient compared to the reference (50-75 nmol/L) in boys, ß = -2.2; 95% confidence interval = [-4.3, -0.1], p = 0.039. The same association with full-scale intelligence quotient was found for early pregnancy serum 25-hydroxyvitamin D, ß = -2.5 [-4.6, -0.3], p = 0.025, primarily driven by an association in boys, ß = -4.0 [-7.2, -0.8], p = 0.015; and for serum 25-hydroxyvitamin D at 7 years in girls, ß = -3.0 [-6.0, -0.1], p = 0.042. CONCLUSION: In this cohort, serum 25-hydroxyvitamin D < 50 nmol/L in both early gestation and cord blood in boys and current serum 25-hydroxyvitamin D < 50 nmol/L in girls were independent risk factors for two to four points lower full-scale intelligence quotient at the age of 7 years. Vulnerability to hypovitaminosis D, especially in pregnancy, may relate to child sex.