Association of Prenatal Maternal Anemia With Neurodevelopmental Disorders

Wiegersma, Aline Marileen; Dalman, Christina; Lee, Brian K.; Karlsson, Håkan; Gardner, Renee M.

doi:10.1001/jamapsychiatry.2019.2309

Cited by 160 publications

(143 citation statements)

References 40 publications

(82 reference statements)

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“…Neonatal iron deficiency has been linked to numerous neurobehavioral effects (4). Most recently, an association was reported between maternal anemia diagnosed earlier in pregnancy (≤30 weeks) and increased offspring risk of autism spectrum disorder, attention-deficit/hyperactivity disorder, and intellectual disability (6). Therefore, it is important that neonatal iron deficiency be accurately quantitated.…”

Section: Discussionmentioning

confidence: 99%

“…Iron is essential for a healthy pregnancy, with approximately 1 gram of iron needed for the expansion of maternal red cell mass and placental and fetal development (1). Severe iron deficiency and iron deficiency anemia during pregnancy have been associated with increased maternal mortality, perinatal death, preterm birth, low birth weight, impaired immune function, and long-term cognitive defects in newborns and infants (2)(3)(4)(5)(6). To prevent these adverse outcomes, the WHO currently recommends daily iron supplementation for all pregnant adolescent and adult women (7).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of maternal iron status on placental and fetal iron homeostasis

Sangkhae¹,

Fisher

Wong³

et al. 2019

Journal of Clinical Investigation

131

195

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of maternal iron status on placental and fetal iron homeostasis

Sangkhae¹,

Fisher

Wong³

et al. 2019

Journal of Clinical Investigation

131

195

View full text Add to dashboard Cite

“…As mentioned previously, timing, dose, and duration of the insufficiency determine the sequelae. In an analysis of over half a million of children in Sweden, it was shown that children of mothers who were diagnosed with anemia in the first 30 weeks of pregnancy had a higher incidence of autism spectrum disorder, ADHD, and intellectual disability relative to children of mothers who were diagnosed later in pregnancy or not diagnosed [26]. Thus, the earlier timing and longer duration of the insufficiency led to more severe and diagnosable issues.…”

Section: Ironmentioning

confidence: 99%

Nutritional Factors in Fetal and Infant Brain Development

Cheatham¹

2019

Ann Nutr Metab

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“…Maternal nutrition is a factor associated with ASD that might plausibly correlate with the presence of AGA. For example, maternal iron deficiency during the early stages of pregnancy has been associated with an increased risk of ASD in offspring (28). Cereals, including wheat, constitute an important source of iron in Sweden (29) and the reduced ASD risk associated with AGA may reflect wheat consumption and adequate iron supplies in a subgroup of women.…”

Section: Potential Mechanism and Implications For Asd Pathogenesismentioning

confidence: 99%

Maternal antibodies to gliadin and autism spectrum disorders in offspring - A population-based case-control study in Sweden

Gardner

Samuelsson

Severance

et al. 2020

Preprint

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ObjectiveIndividuals diagnosed with autism spectrum disorders (ASD) are reported to have higher levels of antibodies directed towards gliadin, a component of wheat gluten. However, no study has examined such antibodies in etiologically-relevant periods before diagnosis. The objective of this study is to investigate if maternal levels of immunoglobulin G antibodies directed at gliadin, during pregnancy and at the time of birth, are associated with ASD in offspring. MethodsIn this population-based study set in Sweden with 921 ASD cases and 1090 controls, we analyzed levels of anti-gliadin antibodies (AGA) in archived neonatal dried blood spots (NDBS, as maternal IgG is transferred to the fetus) and in paired maternal sera collected earlier in pregnancy for a subset of 547 cases and 428 controls. We examined associations to any ASD diagnosis and considering common comorbidities (i.e. intellectual disability [ID] and attentiondeficit/hyperactivity disorder [ADHD]). We compared 206 ASD cases to their unaffected siblings to examine the potential for confounding by shared familial factors. ResultsHigh levels (³90 th percentile) of maternal AGA were associated with decreased odds of ASD, particularly ASD with comorbid ID, when measured in NDBS (OR 0.51, 95% CI 0.30-0.87) with a similar trend in maternal sera (0.55, 0.24-1.29). High levels of maternal AGA were similarly associated with lower odds of ASD with ID in the sibling comparison. ConclusionsThis first study of exposure to AGA in the pre-and perinatal periods suggests that high levels of maternal AGA are associated with lower odds of ASD with ID. SF2. Maternal IgG AGA levels during pregnancy and offspring odds of ASDThe figure displays crude and adjusted OR's and 95 % CI for high levels of maternal AGA (i.e. levels in the 80-90 and > 90 th percentile categories, based on the distribution among controls) when measured in NDBS and in MS, for ASD in offspring as well as for ASD subtyped by comorbidities. The adjusted models for AGA in NDBS were adjusted for sex, maternal age, maternal BMI, maternal psychiatric history, maternal immigrant status, income, birth order, gestational age at birth and mode of delivery. The adjusted models for AGA in MS were adjusted for sex, maternal age, maternal BMI, maternal psychiatric history, maternal immigrant status, income, maternal total IgG and birth order.Abbreviations; ADHD = Attention-deficit hyperactive disorder, AGA = Antigliadin antibodies, ASD = Autism spectrum disorders, CI = Confidence interval, ID =Intellectual disability, MS = Maternal, NDBS = Neonatal dried blood spots, OR = Odds ratio

show abstract

Association of Prenatal Maternal Anemia With Neurodevelopmental Disorders

Cited by 160 publications

References 40 publications

Effects of maternal iron status on placental and fetal iron homeostasis

Effects of maternal iron status on placental and fetal iron homeostasis

Nutritional Factors in Fetal and Infant Brain Development

Maternal antibodies to gliadin and autism spectrum disorders in offspring - A population-based case-control study in Sweden

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