Reproductive stoppage in autism spectrum disorder in a population of 2.5 million individuals.


Journal

Molecular autism
ISSN: 2040-2392
Titre abrégé: Mol Autism
Pays: England
ID NLM: 101534222

Informations de publication

Date de publication:
2019
Historique:
received: 15 05 2018
accepted: 25 11 2019
entrez: 21 12 2019
pubmed: 21 12 2019
medline: 18 6 2020
Statut: epublish

Résumé

It has been suggested that parents of children with autism spectrum disorder (ASD) curtail their reproduction, a phenomenon known as reproductive stoppage. To investigate the presence of reproductive stoppage, we followed the reproduction in mothers of children with or without an ASD diagnosis using Swedish population-based registries. We followed all families with first child born in 1987 or later. In total 2,521,103 children, nested within 1,270,017 mothers, were included. Exposure was presence of ASD diagnosis in earlier born siblings, and outcome was considered as (1) inter-pregnancy interval and (2) number of subsequent children. Analyses of inter-pregnancy intervals showed that the association differed across birth orders, with a lower rate of second children when first child had ASD diagnosis, but an increased rate of third and higher birth orders in families where a previous child had an ASD diagnosis. When all birth orders were simultaneously considered, families with a child with an ASD diagnosis were less likely to have another child (hazard ratio (HR), 0.79; 95% confidence interval [95% CI], 0.78-0.80). However, when adjusted for birth order, the association was close to null (HR, 0.97; 95% CI, 0.96-0.99), and after additional adjustments (maternal age, birth period, sex, paternal age, and maternal education), the association disappeared (HR, 1.00; 95% CI, 0.99-1.02). In analyses of subsequent children, after adjustment for covariates, families with an ASD diagnosis had 4% more subsequent children (rate ratio, 1.04; 95% CI, 1.03-1.05). The study was undertaken in a country with largely tax-funded healthcare; results may not generalize to other societies. Following the current dominating umbrella concept of ASD, we did not differentiate between the ASD sub-diagnoses; it is possible that reproductive patterns can be dependent on ASD subtypes and the severity and composition of ASD phenotypes and comorbidities. This study does not support a universal reproductive stoppage effect in ASD families, when birth order and other factors are considered. Therefore, proper attention to birth order and other factors may alleviate potential bias in familial aggregation studies of ASD.

Sections du résumé

Background
It has been suggested that parents of children with autism spectrum disorder (ASD) curtail their reproduction, a phenomenon known as reproductive stoppage. To investigate the presence of reproductive stoppage, we followed the reproduction in mothers of children with or without an ASD diagnosis using Swedish population-based registries.
Methods
We followed all families with first child born in 1987 or later. In total 2,521,103 children, nested within 1,270,017 mothers, were included. Exposure was presence of ASD diagnosis in earlier born siblings, and outcome was considered as (1) inter-pregnancy interval and (2) number of subsequent children.
Results
Analyses of inter-pregnancy intervals showed that the association differed across birth orders, with a lower rate of second children when first child had ASD diagnosis, but an increased rate of third and higher birth orders in families where a previous child had an ASD diagnosis. When all birth orders were simultaneously considered, families with a child with an ASD diagnosis were less likely to have another child (hazard ratio (HR), 0.79; 95% confidence interval [95% CI], 0.78-0.80). However, when adjusted for birth order, the association was close to null (HR, 0.97; 95% CI, 0.96-0.99), and after additional adjustments (maternal age, birth period, sex, paternal age, and maternal education), the association disappeared (HR, 1.00; 95% CI, 0.99-1.02). In analyses of subsequent children, after adjustment for covariates, families with an ASD diagnosis had 4% more subsequent children (rate ratio, 1.04; 95% CI, 1.03-1.05).
Limitations
The study was undertaken in a country with largely tax-funded healthcare; results may not generalize to other societies. Following the current dominating umbrella concept of ASD, we did not differentiate between the ASD sub-diagnoses; it is possible that reproductive patterns can be dependent on ASD subtypes and the severity and composition of ASD phenotypes and comorbidities.
Conclusions
This study does not support a universal reproductive stoppage effect in ASD families, when birth order and other factors are considered. Therefore, proper attention to birth order and other factors may alleviate potential bias in familial aggregation studies of ASD.

Identifiants

pubmed: 31857873
doi: 10.1186/s13229-019-0300-6
pii: 300
pmc: PMC6907273
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

45

Informations de copyright

© The Author(s). 2019.

Déclaration de conflit d'intérêts

Competing interestsHL has served as a speaker for Evolan and Shire and has received a research grant from Shire, all outside the submitted work. SB has in the last 5 years acted as an author, consultant, or lecturer for Shire, Medice, Roche, Eli Lilly, Prima Psychiatry, GLGroup, System Analytic, Kompetento, Expo Medica, and Prophase. He receives royalties for text books and diagnostic tools from Huber/Hogrefe, Kohlhammer and UTB, all outside the submitted work. PL has served as a speaker for Medicine, all outside of submitted work. No other disclosures are reported.

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Auteurs

Ralf Kuja-Halkola (R)

1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-171 77 Stockholm, Sweden.

Henrik Larsson (H)

1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-171 77 Stockholm, Sweden.
2School of Medical Sciences, Örebro University, Örebro, Sweden.

Sebastian Lundström (S)

3Gillberg Neuropsychiatry Centre; Centre for Ethics, Law and Mental Health, University of Gothenburg, Gothenburg, Sweden.

Sven Sandin (S)

1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-171 77 Stockholm, Sweden.
4Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.
5Seaver Autism Center for Research and Treatment at Mount Sinai, New York, USA.

Azadeh Chizarifard (A)

6Department of Statistics, Stockholm University, Stockholm, Sweden.

Sven Bölte (S)

7Center of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research; Department of Women's and Children's Health, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
9Curtin Autism Research Group, School of Occupational Therapy, Social Work and Speech Pathology, Curtin University, Perth, WA Australia.

Paul Lichtenstein (P)

1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-171 77 Stockholm, Sweden.

Emma Frans (E)

1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-171 77 Stockholm, Sweden.

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