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      Growth of singletons born after frozen embryo transfer until early adulthood: a Finnish register study

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          Abstract

          STUDY QUESTION

          Are there growth differences between singleton children born after frozen embryo transfer (FET), fresh embryo transfer (ET), and natural conception (NC)?

          SUMMARY ANSWER

          Adolescent boys born after FET have a higher mean proportion and increased odds of overweight compared to those born after fresh ET.

          WHAT IS KNOWN ALREADY

          Children born after FET have higher mean birthweights and an increased risk of large-for-gestational-age compared to those born after fresh ET and even NC. This raises questions about possible growth differences later in childhood. Previous studies on child growth after FET report partly conflicting results and lack long-term data until adolescence.

          STUDY DESIGN, SIZE, DURATION

          This was a cohort study based on national population-based registers, the Finnish Medical Birth Register and the Register of Primary Health Care visits, including singletons born after FET (n = 1825), fresh ET (n = 2933), and NC (n = 31 136) in Finland between the years 1995 and 2006.

          PARTICIPANTS/MATERIALS, SETTING, METHODS

          The proportions of overweight (i.e. age- and sex-adjusted ISO-BMI for children 25) were compared between the groups. Odds ratios (ORs) and adjusted odds ratios (aORs) of overweight were calculated. Adjustments were made for birth year, preterm birth, maternal age, parity, and socioeconomic status. Mean heights, weights, and BMIs were compared between the groups each year between the ages of 7 and 18.

          MAIN RESULTS AND THE ROLE OF CHANCE

          FET boys had a higher mean proportion of overweight (28%) compared to fresh ET (22%, P < 0.001) and NC (26%, P = 0.014) boys. For all ages combined, the aOR of overweight was increased (1.14, 95% CI 1.02–1.27) for FET boys compared to fresh ET boys. For girls, the mean proportions of overweight were 18%, 19%, and 22% for those born after FET, fresh ET, and NC, respectively ( P = 0.169 for FET vs fresh ET, P < 0.001 for FET vs NC). For all ages combined, FET girls had a decreased aOR of overweight (0.89, 95% CI 0.80–0.99) compared to NC girls. Growth measurements were available for 6.9% to 30.6% of FET boys and for 4.7% to 29.4% of FET girls at different ages.

          LIMITATIONS, REASONS FOR CAUTION

          Unfortunately, we were not able to adjust for parental anthropometric characteristics. The growth data were not available for the whole cohort, and the proportion of children with available measurements was limited at the start and end of the follow-up. During the study period, mainly cleavage stage embryos were transferred, and slow freezing was used for ART.

          WIDER IMPLICATIONS OF THE FINDINGS

          The risk of overweight among FET boys warrants further research. Future studies should aim to investigate the mechanisms that explain this sex-specific finding and combine growth data with long-term health data to explore the possible risks of overweight and cardiometabolic disease in adulthood.

          STUDY FUNDING/COMPETING INTEREST(S)

          Funding was obtained from the Päivikki and Sakari Sohlberg Foundation, the Alma and K.A. Snellman Foundation (personal grants to A.M.T.), and the Finnish Government Research Funding. The funding sources were not involved in the planning or execution of the study. The authors declare no conflicts of interest.

          TRIAL REGISTRATION NUMBER

          N/A.

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          Most cited references31

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          Establishing a standard definition for child overweight and obesity worldwide: international survey.

          To develop an internationally acceptable definition of child overweight and obesity, specifying the measurement, the reference population, and the age and sex specific cut off points. International survey of six large nationally representative cross sectional growth studies. Brazil, Great Britain, Hong Kong, the Netherlands, Singapore, and the United States. 97 876 males and 94 851 females from birth to 25 years of age. Body mass index (weight/height(2)). For each of the surveys, centile curves were drawn that at age 18 years passed through the widely used cut off points of 25 and 30 kg/m(2) for adult overweight and obesity. The resulting curves were averaged to provide age and sex specific cut off points from 2-18 years. The proposed cut off points, which are less arbitrary and more internationally based than current alternatives, should help to provide internationally comparable prevalence rates of overweight and obesity in children.
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            Is frozen embryo transfer better for mothers and babies? Can cumulative meta-analysis provide a definitive answer?

            Initial observational studies and a systematic review published 5 years ago have suggested that obstetric and perinatal outcomes are better in offspring conceived following frozen rather than fresh embryo transfers, with reduced risks of preterm birth, small for gestational age, low birth weight and pre-eclampsia. More recent primary studies are beginning to challenge some of these findings. We therefore conducted an updated systematic review and cumulative meta-analysis to examine if these results have remained consistent over time.
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              New Finnish growth references for children and adolescents aged 0 to 20 years: Length/height-for-age, weight-for-length/height, and body mass index-for-age.

              Growth curves require regular updates due to secular trends in linear growth. We constructed contemporary growth curves, assessed secular trends in height, and defined body mass index (BMI) cut-off points for thinness, overweight, and obesity in Finnish children. Mixed cross-sectional/longitudinal data of 73,659 healthy subjects aged 0-20 years (born 1983-2008) were collected from providers in the primary health care setting. Growth references for length/height-for-age, weight-for-length/height, and BMI-for-age were fitted using generalized additive models for location, scale, and shape (GAMLSS). BMI percentile curves passing through BMIs 30, 25, 18.5, 17, and 16 kg/m(2) at the age of 18 years were calculated to define limits for obesity, overweight, and various grades of thinness. Increased length/height-for-age was seen in virtually all age-groups when compared to previous Finnish growth data from 1959 to 1971. Adult height was increased by 1.9 cm in girls and 1.8 cm in boys. The largest increases were seen during the peripubertal years: up to 2.8 cm in girls and 5.6 cm in boys. Median weight-for-length/height had not increased. New Finnish references for length/height-for-age, weight-for-length/height, and BMI-for-age were constructed and should be implemented to monitor growth of children in Finland.
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                Author and article information

                Contributors
                Journal
                Hum Reprod
                Hum Reprod
                humrep
                Human Reproduction (Oxford, England)
                Oxford University Press
                0268-1161
                1460-2350
                March 2024
                04 January 2024
                04 January 2024
                : 39
                : 3
                : 604-611
                Affiliations
                Department of Obstetrics and Gynaecology, Research Unit of Clinical Medicine & Medical Research Center Oulu, Oulu University Hospital, University of Oulu , Oulu, Finland
                Department of Obstetrics and Gynaecology, Helsinki University Hospital and University of Helsinki , Helsinki, Finland
                Department of Children and Adolescents, Research Unit of Clinical Medicine & Medical Research Center Oulu, Oulu University Hospital, University of Oulu , Oulu, Finland
                Department of Obstetrics and Gynaecology, Research Unit of Clinical Medicine & Medical Research Center Oulu, Oulu University Hospital, University of Oulu , Oulu, Finland
                Department of Knowledge Brokers, Finnish Institute for Health and Welfare , Helsinki, Finland
                Department of Molecular Medicine and Surgery, Karolinska Institute , Stockholm, Sweden
                Academic Primary Health Care Centre, Region Stockholm , Stockholm, Sweden
                Department of Obstetrics and Gynaecology, Research Unit of Clinical Medicine & Medical Research Center Oulu, Oulu University Hospital, University of Oulu , Oulu, Finland
                Author notes
                Correspondence address. Department of Obstetrics and Gynaecology, Oulu University Hospital, PL 24, 90029 OYS Oulu, Finland. Tel: +358-405354467; E-mail: anna.terho@ 123456fimnet.fi https://orcid.org/0000-0003-3957-3466
                Author information
                https://orcid.org/0000-0003-3957-3466
                https://orcid.org/0000-0003-3088-5594
                https://orcid.org/0000-0001-8254-7525
                https://orcid.org/0000-0001-6272-7043
                Article
                dead264
                10.1093/humrep/dead264
                10905505
                38177081
                d0c273d8-4531-485d-8ff6-085381afd4dd
                © The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 14 July 2023
                : 26 November 2023
                : 14 December 2023
                Page count
                Pages: 8
                Funding
                Funded by: Päivikki and Sakari Sohlberg Foundation, DOI 10.13039/501100004212;
                Funded by: Alma and K.A. Snellman Foundation;
                Funded by: Finnish Government Research Funding;
                Categories
                Original Article
                Reproductive Epidemiology
                AcademicSubjects/MED00905

                Human biology
                art,fet,frozen embryo transfer,child growth,long-term outcome
                Human biology
                art, fet, frozen embryo transfer, child growth, long-term outcome

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