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Intrauterine Growth and Offspring Neurodevelopmental Traits: A Mendelian Randomization Analysis of the Norwegian Mother, Father and Child Cohort Study (MoBa)

IMPORTANCE: Conventional epidemiological analyses have suggested that lower birth weight is associated with later neurodevelopmental difficulties; however, it is unclear whether this association is causal. OBJECTIVE: To investigate the relationship between intrauterine growth and offspring neurodeve...

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Autores principales: D’Urso, Shannon, Moen, Gunn-Helen, Hwang, Liang-Dar, Hannigan, Laurie J., Corfield, Elizabeth C., Ask, Helga, Johannson, Stefan, Njølstad, Pål Rasmus, Beaumont, Robin N., Freathy, Rachel M., Evans, David M., Havdahl, Alexandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10600722/
https://www.ncbi.nlm.nih.gov/pubmed/37878341
http://dx.doi.org/10.1001/jamapsychiatry.2023.3872
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author D’Urso, Shannon
Moen, Gunn-Helen
Hwang, Liang-Dar
Hannigan, Laurie J.
Corfield, Elizabeth C.
Ask, Helga
Johannson, Stefan
Njølstad, Pål Rasmus
Beaumont, Robin N.
Freathy, Rachel M.
Evans, David M.
Havdahl, Alexandra
author_facet D’Urso, Shannon
Moen, Gunn-Helen
Hwang, Liang-Dar
Hannigan, Laurie J.
Corfield, Elizabeth C.
Ask, Helga
Johannson, Stefan
Njølstad, Pål Rasmus
Beaumont, Robin N.
Freathy, Rachel M.
Evans, David M.
Havdahl, Alexandra
author_sort D’Urso, Shannon
collection PubMed
description IMPORTANCE: Conventional epidemiological analyses have suggested that lower birth weight is associated with later neurodevelopmental difficulties; however, it is unclear whether this association is causal. OBJECTIVE: To investigate the relationship between intrauterine growth and offspring neurodevelopmental difficulties. DESIGN, SETTING, AND PARTICIPANTS: MoBa is a population-based pregnancy cohort that recruited pregnant women from June 1999 to December 2008 included approximately 114 500 children, 95 200 mothers, and 75 200 fathers. Observational associations between birth weight and neurodevelopmental difficulties were assessed with a conventional epidemiological approach. Mendelian randomization analyses were performed to investigate the potential causal association between maternal allele scores for birth weight and offspring neurodevelopmental difficulties conditional on offspring allele scores. EXPOSURES: Birth weight and maternal allele scores for birth weight (derived from genetic variants robustly associated with birth weight) were the exposures in the observational and mendelian randomization analyses, respectively. MAIN OUTCOMES AND MEASURES: Clinically relevant maternal ratings of offspring neurodevelopmental difficulties at 6 months, 18 months, 3 years, 5 years, and 8 years of age assessing language and motor difficulties, inattention and hyperactivity-impulsivity, social communication difficulties, and repetitive behaviors. RESULTS: The conventional epidemiological sample included up to 46 970 offspring, whereas the mendelian randomization sample included up to 44 134 offspring (median offspring birth year, 2005 [range, 1999-2009]; mean [SD] maternal age at birth, 30.1 [4.5] years; mean [SD] paternal age at birth, 32.5 [5.1] years). The conventional epidemiological analyses found evidence that birth weight was negatively associated with several domains at multiple offspring ages (outcome of autism-related trait scores: Social Communication Questionnaire [SCQ]–full at 3 years, β = −0.046 [95% CI, −0.057 to −0.034]; SCQ–Restricted and Repetitive Behaviors subscale at 3 years, β = −0.049 [95% CI, −0.060 to −0.038]; attention-deficit/hyperactivity disorder [ADHD] trait scores: Child Behavior Checklist [CBCL]–ADHD subscale at 18 months, β = −0.035 [95% CI, −0.045 to −0.024]; CBCL-ADHD at 3 years, β = −0.032 [95% CI, −0.043 to −0.021]; CBCL-ADHD at 5 years, β = −0.050 [95% CI, −0.064 to −0.037]; Rating Scale for Disruptive Behavior Disorders [RS-DBD]–ADHD at 8 years, β = −0.036 [95% CI, −0.049 to −0.023]; RS-DBD–Inattention at 8 years, β = −0.037 [95% CI, −0.050 to −0.024]; RS-DBD–Hyperactive-Impulsive Behavior at 8 years, β = −0.027 [95% CI, −0.040 to −0.014]; Conners Parent Rating Scale–Revised [Short Form] at 5 years, β = −0.041 [95% CI, −0.054 to −0.028]; motor scores: Ages and Stages Questionnaire–Motor Difficulty [ASQ-MOTOR] at 18 months, β = −0.025 [95% CI, −0.035 to −0.015]; ASQ-MOTOR at 3 years, β = −0.029 [95% CI, −0.040 to −0.018]; and Child Development Inventory–Gross and Fine Motor Skills at 5 years, β = −0.028 [95% CI, −0.042 to −0.015]). Mendelian randomization analyses did not find any evidence for an association between maternal allele scores for birth weight and offspring neurodevelopmental difficulties. CONCLUSIONS AND RELEVANCE: This study found that the maternal intrauterine environment, as proxied by maternal birth weight genetic variants, is unlikely to be a major determinant of offspring neurodevelopmental outcomes.
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spelling pubmed-106007222023-10-27 Intrauterine Growth and Offspring Neurodevelopmental Traits: A Mendelian Randomization Analysis of the Norwegian Mother, Father and Child Cohort Study (MoBa) D’Urso, Shannon Moen, Gunn-Helen Hwang, Liang-Dar Hannigan, Laurie J. Corfield, Elizabeth C. Ask, Helga Johannson, Stefan Njølstad, Pål Rasmus Beaumont, Robin N. Freathy, Rachel M. Evans, David M. Havdahl, Alexandra JAMA Psychiatry Original Investigation IMPORTANCE: Conventional epidemiological analyses have suggested that lower birth weight is associated with later neurodevelopmental difficulties; however, it is unclear whether this association is causal. OBJECTIVE: To investigate the relationship between intrauterine growth and offspring neurodevelopmental difficulties. DESIGN, SETTING, AND PARTICIPANTS: MoBa is a population-based pregnancy cohort that recruited pregnant women from June 1999 to December 2008 included approximately 114 500 children, 95 200 mothers, and 75 200 fathers. Observational associations between birth weight and neurodevelopmental difficulties were assessed with a conventional epidemiological approach. Mendelian randomization analyses were performed to investigate the potential causal association between maternal allele scores for birth weight and offspring neurodevelopmental difficulties conditional on offspring allele scores. EXPOSURES: Birth weight and maternal allele scores for birth weight (derived from genetic variants robustly associated with birth weight) were the exposures in the observational and mendelian randomization analyses, respectively. MAIN OUTCOMES AND MEASURES: Clinically relevant maternal ratings of offspring neurodevelopmental difficulties at 6 months, 18 months, 3 years, 5 years, and 8 years of age assessing language and motor difficulties, inattention and hyperactivity-impulsivity, social communication difficulties, and repetitive behaviors. RESULTS: The conventional epidemiological sample included up to 46 970 offspring, whereas the mendelian randomization sample included up to 44 134 offspring (median offspring birth year, 2005 [range, 1999-2009]; mean [SD] maternal age at birth, 30.1 [4.5] years; mean [SD] paternal age at birth, 32.5 [5.1] years). The conventional epidemiological analyses found evidence that birth weight was negatively associated with several domains at multiple offspring ages (outcome of autism-related trait scores: Social Communication Questionnaire [SCQ]–full at 3 years, β = −0.046 [95% CI, −0.057 to −0.034]; SCQ–Restricted and Repetitive Behaviors subscale at 3 years, β = −0.049 [95% CI, −0.060 to −0.038]; attention-deficit/hyperactivity disorder [ADHD] trait scores: Child Behavior Checklist [CBCL]–ADHD subscale at 18 months, β = −0.035 [95% CI, −0.045 to −0.024]; CBCL-ADHD at 3 years, β = −0.032 [95% CI, −0.043 to −0.021]; CBCL-ADHD at 5 years, β = −0.050 [95% CI, −0.064 to −0.037]; Rating Scale for Disruptive Behavior Disorders [RS-DBD]–ADHD at 8 years, β = −0.036 [95% CI, −0.049 to −0.023]; RS-DBD–Inattention at 8 years, β = −0.037 [95% CI, −0.050 to −0.024]; RS-DBD–Hyperactive-Impulsive Behavior at 8 years, β = −0.027 [95% CI, −0.040 to −0.014]; Conners Parent Rating Scale–Revised [Short Form] at 5 years, β = −0.041 [95% CI, −0.054 to −0.028]; motor scores: Ages and Stages Questionnaire–Motor Difficulty [ASQ-MOTOR] at 18 months, β = −0.025 [95% CI, −0.035 to −0.015]; ASQ-MOTOR at 3 years, β = −0.029 [95% CI, −0.040 to −0.018]; and Child Development Inventory–Gross and Fine Motor Skills at 5 years, β = −0.028 [95% CI, −0.042 to −0.015]). Mendelian randomization analyses did not find any evidence for an association between maternal allele scores for birth weight and offspring neurodevelopmental difficulties. CONCLUSIONS AND RELEVANCE: This study found that the maternal intrauterine environment, as proxied by maternal birth weight genetic variants, is unlikely to be a major determinant of offspring neurodevelopmental outcomes. American Medical Association 2023-10-25 /pmc/articles/PMC10600722/ /pubmed/37878341 http://dx.doi.org/10.1001/jamapsychiatry.2023.3872 Text en Copyright 2023 D’Urso S et al. JAMA Psychiatry. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
D’Urso, Shannon
Moen, Gunn-Helen
Hwang, Liang-Dar
Hannigan, Laurie J.
Corfield, Elizabeth C.
Ask, Helga
Johannson, Stefan
Njølstad, Pål Rasmus
Beaumont, Robin N.
Freathy, Rachel M.
Evans, David M.
Havdahl, Alexandra
Intrauterine Growth and Offspring Neurodevelopmental Traits: A Mendelian Randomization Analysis of the Norwegian Mother, Father and Child Cohort Study (MoBa)
title Intrauterine Growth and Offspring Neurodevelopmental Traits: A Mendelian Randomization Analysis of the Norwegian Mother, Father and Child Cohort Study (MoBa)
title_full Intrauterine Growth and Offspring Neurodevelopmental Traits: A Mendelian Randomization Analysis of the Norwegian Mother, Father and Child Cohort Study (MoBa)
title_fullStr Intrauterine Growth and Offspring Neurodevelopmental Traits: A Mendelian Randomization Analysis of the Norwegian Mother, Father and Child Cohort Study (MoBa)
title_full_unstemmed Intrauterine Growth and Offspring Neurodevelopmental Traits: A Mendelian Randomization Analysis of the Norwegian Mother, Father and Child Cohort Study (MoBa)
title_short Intrauterine Growth and Offspring Neurodevelopmental Traits: A Mendelian Randomization Analysis of the Norwegian Mother, Father and Child Cohort Study (MoBa)
title_sort intrauterine growth and offspring neurodevelopmental traits: a mendelian randomization analysis of the norwegian mother, father and child cohort study (moba)
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10600722/
https://www.ncbi.nlm.nih.gov/pubmed/37878341
http://dx.doi.org/10.1001/jamapsychiatry.2023.3872
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