Association of Exposure to Diethylstilbestrol During Pregnancy With Multigenerational Neurodevelopmental Deficits
- PMID: 29799929
- PMCID: PMC6137513
- DOI: 10.1001/jamapediatrics.2018.0727
Association of Exposure to Diethylstilbestrol During Pregnancy With Multigenerational Neurodevelopmental Deficits
Abstract
Importance: Animal evidence suggests that endocrine disruptors affect germline cells and neurodevelopment. However, to date, the third-generation neurodevelopmental outcomes in humans have not been examined.
Objective: To explore the potential consequences of exposure to diethylstilbestrol or DES across generations-specifically, third-generation neurodevelopment.
Design, setting, and participants: This cohort study uses self-reported health information, such as exposure to diethylstilbestrol during pregnancy and attention-deficit/hyperactivity disorder (ADHD) diagnosis, from 47 540 participants enrolled in the ongoing Nurses' Health Study II. The 3 generations analyzed in this study were the participants (F1 generation), their mothers (F0 generation), and their live-born children (F2 generation).
Main outcomes and measures: Participant- and mother-reported exposure to diethylstilbestrol during pregnancy and physician-diagnosed child ADHD.
Results: The total number of women included in this study was 47 540. Of the 47 540 F0 mothers, 861 (1.8%) used diethylstilbestrol and 46 679 (98.2%) did not while pregnant with the F1 participants. Use of diethylstylbestrol by F0 mothers was associated with an increased risk of ADHD among the F2 generation: 7.7% vs 5.2%, adjusted odds ratio (OR), 1.36 (95% CI, 1.10-1.67) and an OR of 1.63 (95% CI, 1.18-2.25) if diethylstilbestrol was taken during the first trimester of pregnancy. No effect modification was observed by the F2 children's sex.
Conclusions and relevance: This study provides evidence that diethylstilbestrol exposure is associated with multigenerational neurodevelopmental deficits. The doses and potency level of environmental endocrine disruptors to which humans are exposed are lower than those of diethylstilbestrol, but the prevalence of such exposure and the possibility of cumulative action are potentially high and thus warrant consideration.
Conflict of interest statement
Comment in
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Toward an Emerging Paradigm for Understanding Attention-Deficit/Hyperactivity Disorder and Other Neurodevelopmental, Mental, and Behavioral Disorders: Environmental Risks and Epigenetic Associations.JAMA Pediatr. 2018 Jul 1;172(7):619-621. doi: 10.1001/jamapediatrics.2018.0920. JAMA Pediatr. 2018. PMID: 29799950 Free PMC article. No abstract available.
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Pre-conception susceptibility to endocrine disruptors.Nat Rev Endocrinol. 2018 Sep;14(9):505-506. doi: 10.1038/s41574-018-0057-6. Nat Rev Endocrinol. 2018. PMID: 29970916 No abstract available.
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Diethylstilbestrol Exposure in Pregnancy Linked to Multigenerational Neurodevelopmental Deficits.Am J Nurs. 2018 Sep;118(9):65. doi: 10.1097/01.NAJ.0000544982.79172.49. Am J Nurs. 2018. PMID: 30138208 No abstract available.
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Grandmaternal Diethylstilbesterol and Attention-Deficit/Hyperactivity Disorder in Children.JAMA Pediatr. 2018 Dec 1;172(12):1203-1204. doi: 10.1001/jamapediatrics.2018.3740. JAMA Pediatr. 2018. PMID: 30383087 No abstract available.
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Grandmaternal Diethylstilbesterol and Attention-Deficit/Hyperactivity Disorder in Children.JAMA Pediatr. 2018 Dec 1;172(12):1203. doi: 10.1001/jamapediatrics.2018.3737. JAMA Pediatr. 2018. PMID: 30383102 No abstract available.
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Grandmaternal Diethylstilbestrol and Attention-Deficit/Hyperactivity Disorder in Children-Reply.JAMA Pediatr. 2018 Dec 1;172(12):1204-1205. doi: 10.1001/jamapediatrics.2018.3743. JAMA Pediatr. 2018. PMID: 30383104 No abstract available.
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