Dataset Information

Fetal and Infancy Growth Pattern, Cord and Early Childhood Plasma Leptin, and Development of Autism Spectrum Disorder in the Boston Birth Cohort.

ABSTRACT: Leptin is a proinflammatory cytokine that plays an important role in energy homeostasis. Emerging evidence suggests that leptin levels are altered in children with autism spectrum disorder (ASD); however, this has not been studied prospectively. Rapid growth during infancy and early childhood has been implicated in ASD, but the evidence is inconsistent. As leptin is involved in growth and is a potential risk factor for ASD, we explored the associations between (a) cord, early childhood leptin and ASD; and (b) birth weight for gestational age, early childhood weight gain, and ASD. We also assessed the mediating role of leptin in the relationship between weight gain during infancy and ASD. This study was conducted in a sample of 822 subjects from the Boston Birth Cohort. ASD was defined from diagnostic codes in electronic medical records. Extremely rapid weight gain during infancy was associated with a greater ASD risk and this persisted after adjusting for potential confounders (aOR: 3.11; 95% CI: 1.37, 7.07). Similarly, children that had higher plasma leptin levels, prior to ASD diagnosis, had an increased ASD risk in both unadjusted and adjusted models (aOR: 7.87; 95% CI: 2.06, 30.04). Further, early childhood leptin indirectly mediated the relationship between rapid weight gain and ASD. No associations were found between birth weight for gestational age, cord leptin and risk of ASD. Our findings provide a basis to further explore whether the combination of early life growth pattern and a biomarker such as leptin can predict ASD earlier. Autism Res 2018, 11: 1416-1431. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Is early life growth and a biomarker leptin related to ASD risk? To answer this question, we followed 822 children from birth and found that those who gained weight very quickly in infancy, had higher leptin levels in early childhood, had a greater chance of later ASD diagnosis. More research is needed to see if infant's weight gain pattern along with a biomarker (such as leptin) can be used to identify children with ASD sooner.

SUBMITTER: Raghavan R

PROVIDER: S-EPMC6320256 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Fetal and Infancy Growth Pattern, Cord and Early Childhood Plasma Leptin, and Development of Autism Spectrum Disorder in the Boston Birth Cohort.

Raghavan Ramkripa R Zuckerman Barry B Hong Xiumei X Wang Guoying G Ji Yuelong Y Paige David D DiBari Jessica J Zhang Cuilin C Fallin M Daniele MD Wang Xiaobin X

Autism research : official journal of the International Society for Autism Research 20180924 10

Leptin is a proinflammatory cytokine that plays an important role in energy homeostasis. Emerging evidence suggests that leptin levels are altered in children with autism spectrum disorder (ASD); however, this has not been studied prospectively. Rapid growth during infancy and early childhood has been implicated in ASD, but the evidence is inconsistent. As leptin is involved in growth and is a potential risk factor for ASD, we explored the associations between (a) cord, early childhood leptin an ...[more]

PMID: 30248249

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Project description:Autism spectrum disorder (ASD) is phenotypically and etiologically heterogeneous, with evidence for genetic and environmental contributions to disease risk. Research has focused on the prenatal period as a time where environmental exposures are likely to influence risk for ASD. Epidemiological studies have shown significant associations between prenatal exposure to maternal immune activation (MIA), caused by infections and fever, and ASD. However, due to differences in study design and exposure measurements no consistent patterns have emerged revealing specific times or type of MIA exposure that are most important to ASD risk. No prior studies have examined prenatal MIA exposure and ASD risk in an under-represented minority population of African ancestry. To overcome these limitations, we estimated the association between prenatal exposure to fever and maternal infections and ASD in a prospective birth cohort of an understudied minority population in a city in the United States. No association was found between prenatal exposure to genitourinary infections or flu and the risk of ASD in a nested sample of 116 ASD cases and 988 typically developing controls in crude or adjusted analyses. Prenatal exposure to fever was associated with increased ASD risk (aOR 2.02 [1.04-3.92]) after adjustment for educational attainment, marital status, race, child sex, maternal age, birth year, gestational age, and maternal smoking. This effect may be specific to fever during the third trimester (aOR 2.70 [1.00-7.29]). Our findings provide a focus for future research efforts and ASD prevention strategies across diverse populations. Autism Res 2017, 10: 1878-1890. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.Lay summaryWe looked at whether activation of the immune system during pregnancy increases the chance a child will develop ASD. We examined 116 children with ASD and 988 children without ASD that came from a predominantly low income, urban, minority population. We found that having the flu or genitourinary tract infections during pregnancy is not related to the child being diagnosed with ASD. However, we did find children were at increased risk for ASD when their mothers had a fever during pregnancy.

Project description:BackgroundWe previously reported that extremely high concentrations of maternal plasma folate were associated with increased risk of autism spectrum disorder (ASD) in children. This study explored whether specific types of folate in cord blood have differential association with ASD.ObjectivesIn the Boston Birth Cohort (BBC), we assessed the association between cord blood unmetabolized folic acid (UMFA), 5-methyl tetrahydrofolate (THF), and total folate and a child's ASD risk. In a subset, we explored whether the association between UMFA and ASD risk can be affected by the dihydrofolate reductase (DHFR) genotype and cord plasma creatinine. We also examined prenatal correlates of cord UMFA concentrations.MethodsThis report included 567 BBC children (92 ASD, 475 neurotypical), who were recruited at birth and prospectively followed at the Boston Medical Center. ASD was defined from International Classification of Diseases (ICD)-9 and ICD-10 codes documented in electronic medical records.ResultsChildren with cord UMFA in the highest, versus lowest quartile, had a greater ASD risk (adjusted OR, aORquartile4: 2.26; 95% CI: 1.08, 4.75). When stratified by race/ethnicity, the association was limited to 311 (45 ASD) Black children (aORquartile4: 9.85; 95% CI: 2.53, 38.31); a test of interaction between race/ethnicity and cord UMFA concentrations was significant (P = 0.007). The UMFA-ASD association in Black children slightly attenuated after adjusting for cord plasma creatinine (P = 0.05). There was no significant association between cord 5-methyl THF, total folate, DHFR genotype, and ASD risk. Cord total folate and maternal supplement intake during second trimester were associated with higher cord UMFA.ConclusionsHigher concentrations of cord UMFA, but not 5-methyl THF or total folate, were associated with a greater risk of ASD in Black children. This study in a preterm-birth-enriched cohort raises more questions than it could answer and underscores the need for additional investigations on the sources and role of cord UMFA in children's neurodevelopmental outcomes and underlying mechanisms.

Dataset Information

Fetal and Infancy Growth Pattern, Cord and Early Childhood Plasma Leptin, and Development of Autism Spectrum Disorder in the Boston Birth Cohort.

Publications

Fetal and Infancy Growth Pattern, Cord and Early Childhood Plasma Leptin, and Development of Autism Spectrum Disorder in the Boston Birth Cohort.

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