Folate Status of Mothers During Pregnancy and Mental and Psychomotor Development of Their Children at Five Years of Age

Tamura, Tsunenobu; Goldenberg, Robert L.; Chapman, Victoria; Johnston, Kelley E.; Ramey, Sharon L.; Nelson, Kathleen G.

doi:10.1542/peds.2004-2189

Cited by 80 publications

(88 citation statements)

References 26 publications

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“…In contrast to these findings, another longitudinal study assessing folic acid status late in pregnancy found no significant associations with children's neurodevelopment at 5 years of age (15) . This discrepancy may be explained by the time of measuring exposure and the follow-up of a non-population-based Table 2 Association between folic acid intake from supplements in early pregnancy and child neurodevelopment at 18 months of age (n 553), the mother-child cohort 'Rhea' study, Crete Bayely-III, Bayley Scales of Infant and Toddler Development, 3rd edition.…”

Section: Discussionmentioning

confidence: 66%

Effect of high doses of folic acid supplementation in early pregnancy on child neurodevelopment at 18 months of age: the mother–child cohort ‘Rhea’ study in Crete, Greece

Chatzi

Papadopoulou

Koutra

et al. 2012

Public Health Nutr.

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Objective: To investigate whether high doses of folic acid supplementation in early pregnancy are associated with child neurodevelopment at 18 months of age. Design: The study uses data from the prospective mother-child cohort 'Rhea' study. Pregnant women completed an interviewer-administered questionnaire on folic acid supplementation at 14-18 weeks of gestation. Neurodevelopment at 18 months was assessed with the use of the Bayley Scales of Infant and Toddler Development (3rd edition). Red-blood-cell folate concentrations in cord blood were measured in a sub-sample of the study population (n 58). Setting: Heraklion, Crete, Greece, 2007Greece, -2010. Subjects: Five hundred and fifty-three mother-child pairs participating in the 'Rhea' cohort. Results: Sixty-eight per cent of the study participants reported high doses of supplemental folic acid use (5 mg/d), while 24 % reported excessive doses of folic acid (.5 mg/d) in early pregnancy. Compared with non-users, daily intake of 5 mg supplemental folic acid was associated with a 5-unit increase on the scale of receptive communication and a 3?5-unit increase on the scale of expressive communication. Doses of folic acid supplementation higher than 5 mg/d were not associated with additional increase in the neurodevelopmental scales. Conclusions: This is the first prospective study showing that high doses of supplementary folic acid in early pregnancy may be associated with enhanced vocabulary development, communicational skills and verbal comprehension at 18 months of age. Additional longitudinal studies and trials are needed to confirm these results.

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Section: Discussionmentioning

confidence: 66%

Effect of high doses of folic acid supplementation in early pregnancy on child neurodevelopment at 18 months of age: the mother–child cohort ‘Rhea’ study in Crete, Greece

Chatzi

Papadopoulou

Koutra

et al. 2012

Public Health Nutr.

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“…The association between maternal blood folate status and cognitive development has been investigated in several studies (Tamura et al, 2005;Veena et al, 2010). Tamura et al (2005) did not find any relationship between maternal blood folate status ("low" vs. "normal") during the second half of the pregnancy and cognitive development of their children at the age of 5-6 years on different cognitive tests including Differential Ability Scales, Visual and Auditory Sequential Memory, Knox Cube, the Gross Motor Scale and the Grooved Pegboard.…”

Section: Omega-3 Fatty Acidsmentioning

confidence: 99%

The Role of Nutrition in Children's Neurocognitive Development, From Pregnancy Through Childhood

Nyaradi¹,

Li²,

Hickling³

et al. 2015

Prenatal and Childhood Nutrition

129

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This review examines the current evidence for a possible connection between nutritional intake (including micronutrients and whole diet) and neurocognitive development in childhood. Earlier studies which have investigated the association between nutrition and cognitive development have focused on individual micronutrients, including omega-3 fatty acids, vitamin B12, folic acid, choline, iron, iodine, and zinc, and single aspects of diet. The research evidence from observational studies suggests that micronutrients may play an important role in the cognitive development of children. However, the results of intervention trials utilizing single micronutrients are inconclusive. More generally, there is evidence that malnutrition can impair cognitive development, whilst breastfeeding appears to be beneficial for cognition. Eating breakfast is also beneficial for cognition. In contrast, there is currently inconclusive evidence regarding the association between obesity and cognition. Since individuals consume combinations of foods, more recently researchers have become interested in the cognitive impact of diet as a composite measure. Only a few studies to date have investigated the associations between dietary patterns and cognitive development. In future research, more well designed intervention trials are needed, with special consideration given to the interactive effects of nutrients.

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“…However, it is unclear if this mechanism contributes to AED-induced behavioral teratogenesis. Folate deficiency during pregnancy reduces neurogenesis and increases apoptosis [34], but folate nutritional status during pregnancy has not been shown to impact neurodevelopment [35]. As discussed below, there is mounting evidence that AED-induced apoptosis is the most likely candidate for the behavioral deficits.…”

Section: Proposed Mechanismsmentioning

confidence: 99%

Cognitive/behavioral teratogenetic effects of antiepileptic drugs

Meador

Baker

Cohen

et al. 2007

Epilepsy & Behavior

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The majority of children of mothers with epilepsy are normal, but they are at increased risk for developmental delay. Antiepileptic drugs (AEDs) appear to play a role. Our current knowledge is reviewed, including research design issues and recommendations for future research. In animals, exposure of the immature brain to some AEDs can produce widespread neuronal apoptosis and behavioral deficits. The risks of AEDs in humans are less clear, but recent studies raise concerns, especially for valproate. There is a critical need for well-designed systematic research to improve our understanding of AED effects on the fetal brain. KeywordsAntiepileptic drugs; Anticonvulsant drugs; Pregnancy; Teratogenesis; Development; Cognition; Behavior Animal studies on behavioral effects of in utero AED exposureAnimal studies have demonstrated that in utero antiepileptic drug (AED) exposure can produce behavioral as well as anatomical defects, which can occur at dosages lower than those required to produce somatic malformations [1,2]. Gestational or neonatal exposure to benzodiazepines can affect brain chemistry and behavior causing hyperactivity or learning deficits [3,4]. Despite the common use of carbamazepine in humans, very few neurobehavioral studies in animals have been conducted with this AED. In utero carbamazepine exposure did not produce hyperexcitability in primates [5]. Perinatal phenobarbital exposure in rats reduces brain weight [6]. Mice exposed prenatally to phenobarbital have neuronal deficits, reduced brain weight, and impaired development of reflexes, open-field activity, schedule-controlled behavior, spatial learning, and cate-cholamine brain levels [7][8][9][10][11][12]. Gestational or neonatal exposure to phenytoin reduces brain weight [13,14], alters neuronal membranes in the hippocampus [15], delays neurodevelopment [16], and impairs spatial learning and motor coordination [17][18][19][20][21][22][23][24][25]. Hyperactivity has been observed in rats and primates following prenatal exposure to phenytoin [5,23,25]. Gestational primidone in rats produces learning deficits and reduces open-field activity [26]. In utero valproate exposure can alter neuronal membranes [27], decrease brain weight in mice [28], and result in adverse neurobehavioral effects [29,30].

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Folate Status of Mothers During Pregnancy and Mental and Psychomotor Development of Their Children at Five Years of Age

Cited by 80 publications

References 26 publications

Effect of high doses of folic acid supplementation in early pregnancy on child neurodevelopment at 18 months of age: the mother–child cohort ‘Rhea’ study in Crete, Greece

Effect of high doses of folic acid supplementation in early pregnancy on child neurodevelopment at 18 months of age: the mother–child cohort ‘Rhea’ study in Crete, Greece

The Role of Nutrition in Children's Neurocognitive Development, From Pregnancy Through Childhood

Cognitive/behavioral teratogenetic effects of antiepileptic drugs

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