{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T03:47:56Z","timestamp":1793072876023,"version":"4.5.0"},"reference-count":45,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:sec id=\"ab-yoi230079-4\"><jats:title>Importance<\/jats:title><jats:p>Conventional epidemiological analyses have suggested that lower birth weight is associated with later neurodevelopmental difficulties; however, it is unclear whether this association is causal.<\/jats:p><\/jats:sec><jats:sec id=\"ab-yoi230079-5\"><jats:title>Objective<\/jats:title><jats:p>To investigate the relationship between intrauterine growth and offspring neurodevelopmental difficulties.<\/jats:p><\/jats:sec><jats:sec id=\"ab-yoi230079-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>MoBa is a population-based pregnancy cohort that recruited pregnant women from June 1999 to December 2008 included approximately 114\u202f500 children, 95\u202f200 mothers, and 75\u202f200 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.<\/jats:p><\/jats:sec><jats:sec id=\"ab-yoi230079-7\"><jats:title>Exposures<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec id=\"ab-yoi230079-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec id=\"ab-yoi230079-9\"><jats:title>Results<\/jats:title><jats:p>The conventional epidemiological sample included up to 46\u202f970 offspring, whereas the mendelian randomization sample included up to 44\u202f134 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]\u2013full at 3 years, \u03b2\u2009=\u2009\u22120.046 [95% CI, \u22120.057 to \u22120.034]; SCQ\u2013Restricted and Repetitive Behaviors subscale at 3 years, \u03b2\u2009=\u2009\u22120.049 [95% CI, \u22120.060 to \u22120.038]; attention-deficit\/hyperactivity disorder [ADHD] trait scores: Child Behavior Checklist [CBCL]\u2013ADHD subscale at 18 months, \u03b2\u2009=\u2009\u22120.035 [95% CI, \u22120.045 to \u22120.024]; CBCL-ADHD at 3 years, \u03b2\u2009=\u2009\u22120.032 [95% CI, \u22120.043 to \u22120.021]; CBCL-ADHD at 5 years, \u03b2\u2009=\u2009\u22120.050 [95% CI, \u22120.064 to \u22120.037]; Rating Scale for Disruptive Behavior Disorders [RS-DBD]\u2013ADHD at 8 years, \u03b2\u2009=\u2009\u22120.036 [95% CI, \u22120.049 to \u22120.023]; RS-DBD\u2013Inattention at 8 years, \u03b2\u2009=\u2009\u22120.037 [95% CI, \u22120.050 to \u22120.024]; RS-DBD\u2013Hyperactive-Impulsive Behavior at 8 years, \u03b2\u2009=\u2009\u22120.027 [95% CI, \u22120.040 to \u22120.014]; Conners Parent Rating Scale\u2013Revised [Short Form] at 5 years, \u03b2\u2009=\u2009\u22120.041 [95% CI, \u22120.054 to \u22120.028]; motor scores: Ages and Stages Questionnaire\u2013Motor Difficulty [ASQ-MOTOR] at 18 months, \u03b2\u2009=\u2009\u22120.025 [95% CI, \u22120.035 to \u22120.015]; ASQ-MOTOR at 3 years, \u03b2\u2009=\u2009\u22120.029 [95% CI, \u22120.040 to \u22120.018]; and Child Development Inventory\u2013Gross and Fine Motor Skills at 5 years, \u03b2\u2009=\u2009\u22120.028 [95% CI, \u22120.042 to \u22120.015]). Mendelian randomization analyses did not find any evidence for an association between maternal allele scores for birth weight and offspring neurodevelopmental difficulties.<\/jats:p><\/jats:sec><jats:sec id=\"ab-yoi230079-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2023.3872","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T15:33:23Z","timestamp":1698248003000},"page":"144","source":"Crossref","is-referenced-by-count":19,"title":["Intrauterine Growth and Offspring Neurodevelopmental Traits"],"prefix":"10.1001","volume":"81","author":[{"given":"Shannon","family":"D\u2019Urso","sequence":"first","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunn-Helen","family":"Moen","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia"},{"name":"Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway"},{"name":"K. 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