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Associations between antenatal corticosteroid exposure and neurodevelopment in infants

  • Shiyao Tao
    Affiliations
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
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  • Jiangbo Du
    Affiliations
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China

    State Key Laboratory of Reproductive Medicine (Suzhou Centre), Nanjing Medical University Affiliated Suzhou Hospital, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China
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  • Xia Chi
    Affiliations
    Department of Child Health Care, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, China
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  • Yeyi Zhu
    Affiliations
    Division of Research, Kaiser Permanente Northern California, Oakland, CA
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  • Xiaoyan Wang
    Affiliations
    Department of Obstetrics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China
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  • Qingxia Meng
    Affiliations
    State Key Laboratory of Reproductive Medicine (Suzhou Centre), Nanjing Medical University Affiliated Suzhou Hospital, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China

    Reproductive Genetic Center, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China
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  • Xiufeng Ling
    Affiliations
    Department of Reproduction, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, China
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  • Feiyang Diao
    Affiliations
    Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, Jiangsu, China
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  • Ci Song
    Affiliations
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
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  • Yangqian Jiang
    Affiliations
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
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  • Hong Lv
    Affiliations
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China

    State Key Laboratory of Reproductive Medicine (Suzhou Centre), Nanjing Medical University Affiliated Suzhou Hospital, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China
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  • Qun Lu
    Affiliations
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
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  • Rui Qin
    Affiliations
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
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  • Lei Huang
    Affiliations
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
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  • Xin Xu
    Affiliations
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
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  • Cong Liu
    Affiliations
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
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  • Yuqing Ding
    Affiliations
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
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  • Tao Jiang
    Affiliations
    Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
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  • Hongxia Ma
    Affiliations
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China

    State Key Laboratory of Reproductive Medicine (Suzhou Centre), Nanjing Medical University Affiliated Suzhou Hospital, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China
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  • Yankai Xia
    Affiliations
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China

    Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
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  • Jiayin Liu
    Affiliations
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China

    State Key Laboratory of Reproductive Medicine (Suzhou Centre), Nanjing Medical University Affiliated Suzhou Hospital, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China

    Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, Jiangsu, China
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  • Yuan Lin
    Affiliations
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China

    State Key Laboratory of Reproductive Medicine (Suzhou Centre), Nanjing Medical University Affiliated Suzhou Hospital, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China

    Department of Maternal, Child, and Adolescent Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
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  • Guangfu Jin
    Affiliations
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China

    State Key Laboratory of Reproductive Medicine (Suzhou Centre), Nanjing Medical University Affiliated Suzhou Hospital, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China
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  • Zhibin Hu
    Correspondence
    Corresponding authors: Zhibin Hu, PhD. ; Guangfu Jin, PhD. ; Yuan Lin, PhD
    Affiliations
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China

    State Key Laboratory of Reproductive Medicine (Suzhou Centre), Nanjing Medical University Affiliated Suzhou Hospital, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China
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  • On behalf of theChina National Birth Cohort (CNBC Study Group)

      Background

      It has been well recognized that antenatal administration of dexamethasone to pregnant women at risk of preterm delivery may markedly accelerate fetal maturation and reduce the risk of adverse perinatal outcomes in their preterm infants, particularly for births before 34 weeks of gestation. Since 2015, antenatal corticosteroid administration has been extended beyond 34 weeks of gestation by clinical guidelines, as it might have beneficial effects on fetal maturation and perinatal outcomes. However, concerns regarding the potential influence of antenatal corticosteroid treatment on offspring neurodevelopment have been raised.

      Objective

      This study aimed to investigate whether maternal antenatal corticosteroid administration was associated with neurodevelopment in infants at 1 year of age.

      Study Design

      In this prospective and longitudinal birth cohort study, women were followed up throughout gestation, and their infants underwent a Bayley Scales of Infant and Toddler Development, Third Edition, screening test at 1 year of age between December 2018 and September 2020. Finally, 1609 pregnant women and 1759 infants were included in the current study. Using a generalized linear mixed model, we examined the association between antenatal corticosteroid exposure and infant neurodevelopment in cognitive, receptive communication, expressive communication, fine motor, and gross motor functions.

      Results

      Of the 1759 infants eligible for this study, 1453 (82.6%) were singletons. A total of 710 infants were exposed to antenatal corticosteroids, among whom 415 were dexamethasone exposed and 483 were prednisone exposed. Dexamethasone was prescribed most often in late pregnancy, whereas prednisone was often used before 8 weeks of gestation among women who conceived through assisted reproductive technology. Compared with those who had no exposure, antenatal corticosteroid exposure was associated with an increased risk of infants being noncompetent in the cognitive development domain after adjusting for conventional risk factors (adjusted risk ratio, 1.53; 95% confidence interval, 1.08–2.18; P=.017). For medication-specific exposure, those exposed vs not exposed to antenatal dexamethasone were 1.62-fold (95% confidence interval, 1.10–2.38; P=.014) more likely to be noncompetent in the cognitive development domain at 1 year. The association did not vary markedly between preterm and term infants, singletons and twins, or assisted reproductive technology–conceived and spontaneously conceived infants (all P>.05 for heterogeneity). In contrast, a null association was observed for the risk of being noncompetent in any domain of neurodevelopment with antenatal prednisone exposure at early pregnancy.

      Conclusion

      Here, antenatal corticosteroid, particularly dexamethasone exposure, was markedly associated with an increased risk of infants being noncompetent in the cognitive development domain at 1 year of age. These findings may provide new information when weighing the benefits and potential risks of maternal antenatal corticosteroid administration.

      Key words

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