Hemoglobin A<sub>1c</sub> Levels During Pregnancy and Risk of Autism Spectrum Disorders in Offspring

Xiang, Anny H.; Chow, Ting; Martinez, Mayra P.; Getahun, Darios; Page, Kathleen A.; Buchanan, Thomas A.; R, Feldman

doi:10.1001/jama.2019.8584

Cited by 9 publications

(8 citation statements)

References 3 publications

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“…Potential outliers and data errors were rectified by cross-checking against historical data in the EMR. Validation of the data was established in previous reports …”

Section: Methodsmentioning

confidence: 95%

“…A clinical diagnosis of ASD is based on pediatric developmental specialist evaluations. Methods to obtain the demographic characteristics, covariates, and ASD diagnoses in children have been described in previously published studies on the association between maternal diabetes during pregnancy and risk of ASD in children, which broadly represent the Southern California population . The KPSC Institutional Review Board approved this study and waived individual participant consent; as it was a data-only study, institutional safeguards to maintain risk were well detailed, including deidentification of patient information, the research involved minimal risk to participants, and the waiver would not adversely affect the rights and welfare of participants.…”

Section: Methodsmentioning

confidence: 99%

“…Data were derived from a large birth cohort from an integrated health care system with standard clinical practices and comprehensive electronic medical records. Part of the cohort has been used in previous studies of the association between maternal diabetes and risk of ASD in offspring …”

Section: Introductionmentioning

confidence: 99%

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Association Between Epidural Analgesia During Labor and Risk of Autism Spectrum Disorders in Offspring

et al. 2020

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IMPORTANCEAlthough the safety of labor epidural analgesia (LEA) for neonates has been well documented, the long-term health effects of LEA on offspring remain to be investigated. OBJECTIVE To assess the association between maternal LEA exposure and risk of autism spectrum disorders (ASDs) in offspring.DESIGN, SETTING, AND PARTICIPANTS Data for this retrospective longitudinal birth cohort study were derived from electronic medical records from a population-based clinical birth cohort. A total of 147 895 singleton children delivered vaginally between January 1, 2008, and December 31, 2015, in a single integrated health care system were included. Children were followed up from the age of 1 year until the first date of the following occurrences: clinical diagnosis of ASD, last date of health plan enrollment, death, or the study end date of December 31, 2018.EXPOSURES Use and duration of LEA. MAIN OUTCOMES AND MEASURESThe main outcome was clinical diagnosis of ASD. Cox proportional hazards regression analysis was used to estimate the hazard ratio (HR) of ASD associated with LEA exposure. RESULTS Among the cohort of 147 895 singleton children (74 425 boys [50.3%]; mean [SD] gestational age at delivery, 38.9 [1.5] weeks), 109 719 (74.2%) were exposed to maternal LEA. Fever during labor was observed in 13 055 mothers (11.9%) in the LEA group and 510 of 38 176 mothers (1.3%) in the non-LEA group. Autism spectrum disorders were diagnosed in 2039 children (1.9%) in the LEA group and 485 children (1.3%) in the non-LEA group. After adjusting for potential confounders, including birth year, medical center, maternal age at delivery, parity, race/ethnicity, educational level, household income, history of comorbidity, diabetes during pregnancy, smoking during pregnancy, preeclampsia or eclampsia, prepregnancy body mass index, gestational weight gain, gestational age at delivery, and birth weight, the HR associated with LEA vs non-LEA exposure was 1.37 (95% CI, 1.23-1.53). Relative to the unexposed group, the adjusted HR associated with LEA exposure of less than 4 hours was 1.33 (95% CI, 1.17-1.53), with LEA exposure of 4 to 8 hours was 1.35 (95% CI, 1.20-1.53), and with LEA exposure of more than 8 hours was 1.46 (95% CI, 1.27-1.69). Within the LEA group, there was a significant trend of ASD risk associated with increasing duration of LEA exposure after adjusting for covariates (HR for linear trend, 1.05 [95% CI, 1.01-1.09] per 4 hours). Adding fever to the model did not change the HR estimate associated with LEA exposure (adjusted HR for LEA vs non-LEA, 1.37 [95% CI, 1.22-1.53]).CONCLUSIONS AND RELEVANCE This study suggests that maternal LEA may be associated with increased ASD risk in children. The risk appears to not be directly associated with epidural-related maternal fever.

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“…Potential outliers and data errors were rectified by cross-checking against historical data in the EMR. Validation of the data was established in previous reports …”

Section: Methodsmentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

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Association Between Epidural Analgesia During Labor and Risk of Autism Spectrum Disorders in Offspring

et al. 2020

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“…Therefore, antioxidative pathways, such as Nrf2/HO-1 discovered in this study, with active involvement in dyslipidemia and diabetes, are extremely likely to possess similar properties in preventing and treating GDM. Metformin and insulin are the two major drugs prescribed to treat GDM; however, the clinical practice of insulin is hindered by the inconvenient administration route as well as the potential to become hypoglycaemic and to gain weight (1,5,3). Our data demonstrated that H/R treatment markedly alleviated GDM symptoms via the activation of anti-oxidant enzymes (SOD, GPx and CAT) and restoration of the Nrf2/HO-1 signaling pathway.…”

Section: Discussionmentioning

confidence: 69%

“…GDM causes higher risks of diabetes, obesity and premature cardiovascular system disease during pregnancy for the fetus as well as the mother (3,2). GDM may also lead to deficits in fetal development, with ~15-45% of babies born by diabetic women exhibiting macrosomia symptoms (4,5).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-reoxygenation treatment attenuates gestational diabetes mellitus

Hou

Zhang

et al. 2021

Endocrine Connections

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Background: Oxidative stress leads to insulin resistance and gestational diabetes mellitus (GDM). The nuclear factor erythroid 2-related factor 2 (Nrf2) / heme oxygenase-1 (HO-1) signaling is an important anti-oxidative stress pathway, which can be activated by hypoxia‑reoxygenation (H/R) treatment. We aimed to demonstrate the effects of H/R treatment on GDM symptoms as well as reproductive outcomes. Methods: Pregnant C57BL/KsJ db/+ mice were used as a genetic GDM model. Plasma insulin and other biochemical indexes of plasma, insulin sensitivity, glucose intolerance, blood glucose and liver biochemical indexes were evaluated. Protein abundance of HO-1 and Nrf2 were assessed with Western blot. Results: H/R treatment markedly ameliorated β-cell insufficiency and glucose intolerance, suppressed oxidative stress in vivo, stimulated the activities of anti-oxidant enzymes, and led to improved reproductive outcomes. The beneficial effects of H/R treatment were mechanistically mediated via the restoration of Nrf2/HO-1 anti-oxidant signaling pathway in the liver of GDM mice. Conclusion: Our study, for the first time, suggests that H/R treatment is a potentially novel therapeutic approach against GDM symptoms, by activating the Nrf2/HO-1 signaling pathway and inhibiting oxidative stress.

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Gestational diabetes mellitus and risk of neurodevelopmental disorders in young offspring: does the risk differ by race and ethnicity?

Liu,

Zhu,

Seamans

et al. 2024

American Journal of Obstetrics & Gynecology MFM

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Hemoglobin A_1c Levels During Pregnancy and Risk of Autism Spectrum Disorders in Offspring

Cited by 9 publications

References 3 publications

Association Between Epidural Analgesia During Labor and Risk of Autism Spectrum Disorders in Offspring

Association Between Epidural Analgesia During Labor and Risk of Autism Spectrum Disorders in Offspring

Hypoxia-reoxygenation treatment attenuates gestational diabetes mellitus

Gestational diabetes mellitus and risk of neurodevelopmental disorders in young offspring: does the risk differ by race and ethnicity?

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Hemoglobin A1c Levels During Pregnancy and Risk of Autism Spectrum Disorders in Offspring

Cited by 9 publications

References 3 publications

Association Between Epidural Analgesia During Labor and Risk of Autism Spectrum Disorders in Offspring

Association Between Epidural Analgesia During Labor and Risk of Autism Spectrum Disorders in Offspring

Hypoxia-reoxygenation treatment attenuates gestational diabetes mellitus

Gestational diabetes mellitus and risk of neurodevelopmental disorders in young offspring: does the risk differ by race and ethnicity?

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Hemoglobin A_1c Levels During Pregnancy and Risk of Autism Spectrum Disorders in Offspring