Prenatal vitamin A supplementation associated with adverse child behavior at 3 years in a prospective birth cohort in <scp>Japan</scp>

Ishikawa, Yohei; Tanaka, Haruka; Akutsu, Taisuke; Koide, Kentaro; Sakuma, Mio; Okazaki, Masanori; Ida, Hiroyuki; Urashima, Mitsuyoshi

doi:10.1111/ped.12925

Cited by 6 publications

(5 citation statements)

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“…The VAS group also had poorer weight gain and smaller lower arm circumference. A prospective birth cohort study in Japan showed that supplemental vitamin A intake prior to and/or during pregnancy was significantly associated with disturbed behavior at three years of age, after adjustment for numerous factors (age, number of deliveries, infertility treatment, consumption of fast food, smoking status, maternal and paternal education and income, gestational age at birth, infant’s weight, height, head circumference and body circumference, and the State-Trait Anxiety Inventory at age three) [177].…”

Section: Could Other Risk Factors Be Involved?mentioning

confidence: 99%

Rubella Virus Infection, the Congenital Rubella Syndrome, and the Link to Autism

Mawson

Croft

2019

IJERPH

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Rubella is a systemic virus infection that is usually mild. It can, however, cause severe birth defects known as the congenital rubella syndrome (CRS) when infection occurs early in pregnancy. As many as 8%–13% of children with CRS developed autism during the rubella epidemic of the 1960s compared to the background rate of about 1 new case per 5000 children. Rubella infection and CRS are now rare in the U.S. and in Europe due to widespread vaccination. However, autism rates have risen dramatically in recent decades to about 3% of children today, with many cases appearing after a period of normal development (‘regressive autism’). Evidence is reviewed here suggesting that the signs and symptoms of rubella may be due to alterations in the hepatic metabolism of vitamin A (retinoids), precipitated by the acute phase of the infection. The infection causes mild liver dysfunction and the spillage of stored vitamin A compounds into the circulation, resulting in an endogenous form of hypervitaminosis A. Given that vitamin A is a known teratogen, it is suggested that rubella infection occurring in the early weeks of pregnancy causes CRS through maternal liver dysfunction and exposure of the developing fetus to excessive vitamin A. On this view, the multiple manifestations of CRS and associated autism represent endogenous forms of hypervitaminosis A. It is further proposed that regressive autism results primarily from post-natal influences of a liver-damaging nature and exposure to excess vitamin A, inducing CRS-like features as a function of vitamin A toxicity, but without the associated dysmorphogenesis. A number of environmental factors are discussed that may plausibly be candidates for this role, and suggestions are offered for testing the model. The model also suggests a number of measures that may be effective both in reducing the risk of fetal CRS in women who acquire rubella in their first trimester and in reversing or minimizing regressive autism among children in whom the diagnosis is suspected or confirmed.

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Section: Could Other Risk Factors Be Involved?mentioning

confidence: 99%

Rubella Virus Infection, the Congenital Rubella Syndrome, and the Link to Autism

Mawson

Croft

2019

IJERPH

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“…Numerous studies suggest that there may be beneficial effects of maternal diet in pregnancy on child neurodevelopment, albeit, again with mixed results ( Borge et al, 2017 ). Intakes of antioxidants, n-3 fatty acids, and foods rich in these nutrients have been associated with child developmental outcomes with inconsistent findings ( Guxens et al, 2012 ; Brew et al, 2015 ; Delgado-Noguera et al, 2015 ; Emmett et al, 2015 ; Bolduc et al, 2016 ; Catena et al, 2016 ; Ishikawa et al, 2016 ; Julvez et al, 2016 ; Bruce-Keller et al, 2017 ; Lipton et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Periconceptional Maternal Mediterranean Diet Is Associated With Favorable Offspring Behaviors and Altered CpG Methylation of Imprinted Genes

House

Mendez

Maguire

et al. 2018

Front. Cell Dev. Biol.

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Background: Maternal diet during pregnancy has been shown to influence the child neuro-developmental outcomes. Studies examining effects of dietary patterns on offspring behavior are sparse.Objective: Determine if maternal adherence to a Mediterranean diet is associated with child behavioral outcomes assessed early in life, and to evaluate the role of differentially methylated regions (DMRs) regulating genomically imprinted genes in these associations.Methods: Among 325 mother/infant pairs, we used regression models to evaluate the association between tertiles of maternal periconceptional Mediterranean diet adherence (MDA) scores derived from a Food Frequency Questionnaire, and social and emotional scores derived from the Infant Toddler Social and Emotional Assessment (ITSEA) questionnaire in the second year of life. Methylation of nine genomically imprinted genes was measured to determine if MDA was associated with CpG methylation.Results: Child depression was inversely associated with maternal MDA (Bonferroni-corrected p = 0.041). While controlling for false-discovery, compared to offspring of women with the lowest MDA tertile, those with MDA scores in middle and high MDA tertiles had decreased odds for atypical behaviors [OR (95% CI) = 0.40 (0.20, 0.78) for middle and 0.40 (0.17, 0.92) for highest tertile], for maladaptive behaviors [0.37 (0.18, 0.72) for middle tertile and 0.42 (0.18, 0.95) for highest tertile] and for an index of autism spectrum disorder behaviors [0.46 (0.23, 0.90) for middle and 0.35 (0.15, 0.80) for highest tertile]. Offspring of women with the highest MDA tertile were less likely to exhibit depressive [OR = 0.28 (0.12, 0.64)] and anxiety [0.42 (0.18, 0.97)] behaviors and increased odds of social relatedness [2.31 (1.04, 5.19)] behaviors when compared to low MDA mothers. Some associations varied by sex. Perinatal MDA score was associated with methylation differences for imprinted control regions of PEG10/SGCE [females: Beta (95% CI) = 1.66 (0.52, 2.80) – Bonferroni-corrected p = 0.048; males: -0.56 (-1.13, -0.00)], as well as both MEG3 and IGF2 in males [0.97 (0.00, 1.94)] and -0.92 (-1.65, -0.19) respectively.Conclusion: In this ethnically diverse cohort, maternal adherence to a Mediterranean diet in early pregnancy was associated with favorable neurobehavioral outcomes in early childhood and with sex-dependent methylation differences of MEG3, IGF2, and SGCE/PEG10 DMRs.

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“…In humans, excess VA intake in pregnancy has also been associated with increased risk of birth defects ( 160 ). A birth cohort study in Japan found an association between prepregnancy or antenatal VA and β-carotene supplementation and worsened child behavior at 3 y of age ( 161 ).…”

Section: Resultsmentioning

confidence: 99%

Vitamin A Requirements in Pregnancy and Lactation

Gannon

Jones

Mehta

2020

Current Developments in Nutrition

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Pregnancy and lactation are critical life stages with unique nutritional requirements, including for vitamin A (VA). Current Dietary Reference Intakes (DRIs) for VA were published in 2001. The objective of this review was to identify and categorize evidence related to VA requirements in pregnancy and lactation since these DRIs were formulated. We searched MEDLINE and included articles according to an analytic framework of maternal VA exposure on status and health outcomes in the mother-child dyad. Intermediate and indirect evidence supports that maternal VA intakes can impact the mother's VA status, breastmilk, and health outcomes, as well as the child's VA status and select health outcomes. Food-based approaches may lead to more sustained, sufficient VA status in mothers and children. Research needs include further study linking maternal VA intakes on maternal and child VA status, and further associations with outcomes to determine intake requirements to optimize health.

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Prenatal vitamin A supplementation associated with adverse child behavior at 3 years in a prospective birth cohort in Japan

Abstract: Intake of supplemental vitamin A prior to and/or during pregnancy may worsen child behavior at 3 years of age.

Cited by 6 publications

References 28 publications

Rubella Virus Infection, the Congenital Rubella Syndrome, and the Link to Autism

Rubella Virus Infection, the Congenital Rubella Syndrome, and the Link to Autism

Periconceptional Maternal Mediterranean Diet Is Associated With Favorable Offspring Behaviors and Altered CpG Methylation of Imprinted Genes

Vitamin A Requirements in Pregnancy and Lactation

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