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      Gestational age at birth and cognitive outcomes in adolescence: population based full sibling cohort study

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      1 , 2 , , 2 , 3 , 4 , 5 , 6
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          Abstract

          Objective

          To investigate the association between gestational age at birth and cognitive outcomes in adolescence.

          Design

          Nationwide population based full sibling cohort study.

          Setting

          Denmark.

          Participants

          1.2 million children born between 1 January 1986 and 31 December 2003, of whom 792 724 had one or more full siblings born in the same period.

          Main outcome measures

          Scores in written language (Danish) and mathematics examinations as graded by masked assessors at the end of compulsory schooling (ninth grade, ages 15-16 years), in addition to intelligence test score at military conscription (predominantly at age 18 years) for a nested sub-cohort of male adolescents. School grades were standardised as z scores according to year of examination, and intelligence test scores were standardised as z scores according to year of birth.

          Results

          Among 792 724 full siblings in the cohort, 44 322 (5.6%) were born before 37+0 weeks of gestation. After adjusting for multiple confounders (sex, birth weight, malformations, parental age at birth, parental educational level, and number of older siblings) and shared family factors between siblings, only children born at <34 gestational weeks showed reduced mean grades in written language (z score difference −0.10 (95% confidence interval −0.20 to −0.01) for ≤27 gestational weeks) and mathematics (−0.05 (−0.08 to −0.01) for 32-33 gestational weeks, −0.13 (−0.17 to −0.09) for 28-31 gestational weeks, and −0.23 (−0.32 to −0.15) for ≤27 gestational weeks), compared with children born at 40 gestational weeks. In a nested sub-cohort of full brothers with intelligence test scores, those born at 32-33, 28-31, and ≤27 gestational weeks showed a reduction in IQ points of 2.4 (95% confidence interval 1.1 to 3.6), 3.8 (2.3 to 5.3), and 4.2 (0.8 to 7.5), respectively, whereas children born at 34-39 gestational weeks showed a reduction in intelligence of <1 IQ point, compared with children born at 40 gestational weeks.

          Conclusions

          Cognitive outcomes in adolescence did not differ between those born at 34-39 gestational weeks and those born at 40 gestational weeks, whereas those with a gestational age of <34 weeks showed substantial deficits in multiple cognitive domains.

          Related collections

          Most cited references32

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          The Danish Civil Registration System as a tool in epidemiology.

          The methodological advances in epidemiology have facilitated the use of the Danish Civil Registration System (CRS) in ways not previously described systematically. We reviewed the CRS and its use as a research tool in epidemiology. We obtained information from the Danish Law on Civil Registration and the Central Office of Civil Registration, and used existing literature to provide illustrative examples of its use. The CRS is an administrative register established on April 2, 1968. It contains individual-level information on all persons residing in Denmark (and Greenland as of May 1, 1972). By January 2014, the CRS had cumulatively registered 9.5 million individuals and more than 400 million person-years of follow-up. A unique ten-digit Civil Personal Register number assigned to all persons in the CRS allows for technically easy, cost-effective, and unambiguous individual-level record linkage of Danish registers. Daily updated information on migration and vital status allows for nationwide cohort studies with virtually complete long-term follow-up on emigration and death. The CRS facilitates sampling of general population comparison cohorts, controls in case-control studies, family cohorts, and target groups in population surveys. The data in the CRS are virtually complete, have high accuracy, and can be retrieved for research purposes while protecting the anonymity of Danish residents. In conclusion, the CRS is a key tool for epidemiological research in Denmark.
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            The nature of nurture: Effects of parental genotypes

            Sequence variants in the parental genomes that are not transmitted to a child (the proband) are often ignored in genetic studies. Here we show that nontransmitted alleles can affect a child through their impacts on the parents and other relatives, a phenomenon we call "genetic nurture." Using results from a meta-analysis of educational attainment, we find that the polygenic score computed for the nontransmitted alleles of 21,637 probands with at least one parent genotyped has an estimated effect on the educational attainment of the proband that is 29.9% (P = 1.6 × 10-14) of that of the transmitted polygenic score. Genetic nurturing effects of this polygenic score extend to other traits. Paternal and maternal polygenic scores have similar effects on educational attainment, but mothers contribute more than fathers to nutrition- and heath-related traits.
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              Danish Education Registers.

              Collection of systematic information on education is a long-established practice in Denmark. We describe the education registers available through Statistics Denmark. In particular, we describe the most widely used register: the Population Education Register (PER). In 2008, 96% of the Danish population aged 15-69 have non-missing education information in PER. For the immigrant population born in the same cohorts the coverage is 85-90%, which is a high coverage in an international context. The validity and coverage of the Danish education registers are very high.
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                Author and article information

                Contributors
                Role: physician
                Role: chief statistician
                Role: research director
                Journal
                BMJ
                BMJ
                BMJ-UK
                bmj
                The BMJ
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2023
                18 January 2023
                : 380
                : e072779
                Affiliations
                [1 ]Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, UK
                [2 ]Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
                [3 ]Center for Fertility and Health, Norwegian Institute of Public Health, Norway
                [4 ]K.G. Jebsen Center for Genetic Epidemiology, Norwegian University for Science and Technology, Norway
                [5 ]Department of Genetics, Stanford University School of Medicine, CA, USA
                [6 ]Danish Cancer Society Research Center, Copenhagen, Denmark
                Author notes
                Correspondence to: A Husby Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark andh@ 123456ssi.dk
                Author information
                https://orcid.org/0000-0002-7634-8455
                https://orcid.org/0000-0002-0019-2247
                https://orcid.org/0000-0001-8264-6785
                Article
                bmj-2022-072779.R1 husa072779
                10.1136/bmj-2022-072779
                9846680
                36653028
                98023558-911f-461b-a405-d6d43c8754a6
                © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 21 December 2022
                Categories
                Research

                Medicine
                Medicine

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