PMID- 38113196 OWN - NLM STAT- MEDLINE DCOM- 20231221 LR - 20240210 IS - 1549-1676 (Electronic) IS - 1549-1277 (Print) IS - 1549-1277 (Linking) VI - 20 IP - 12 DP - 2023 Dec TI - Overweight or obesity in children born after assisted reproductive technologies in Denmark: A population-based cohort study. PG - e1004324 LID - 10.1371/journal.pmed.1004324 [doi] LID - e1004324 AB - BACKGROUND: The association between assisted reproductive technologies (ARTs) and the body mass index (BMI) of children remains controversial. Confounding by morbidity and other factors associated with parental infertility may have biased studies comparing children born after ART with children born after no treatment. We investigated the associations between different fertility treatments and BMI in children at age 5 to 8 years, adjusting for and stratifying by causes of parental infertility. METHODS AND FINDINGS: This Danish cohort study included 327,301 children born between 2007 and 2012 (51% males, median age at follow-up 7 years). Of these, 13,675 were born after ART, 7,728 were born after ovulation induction with or without intrauterine insemination [OI/IUI], and 305,898 were born after no fertility treatments. Using the International Obesity Task Force (IOTF) standards, we defined overweight (BMI >/= IOTF-25) and obesity (BMI >/= IOTF-30). We compared children born after ART versus OI/IUI; intracytoplasmic sperm injection (ICSI) versus conventional in vitro fertilization (IVF); and frozen-thawed versus fresh embryo transfer and estimated crude and adjusted prevalences of children with overweight or obesity at age 5 to 8 years, prevalence odds ratios (PORs), and differences in mean BMI z-scores. Adjustment was performed using stabilized inverse probability of treatment weights, including parity, year of conception, parental causes of infertility, age, educational level, comorbidities, maternal country of origin, BMI, and smoking as covariates. The crude prevalence of obesity was 1.9% in children born after ART, 2.0% in those born after OI/IUI, and 2.7% in those born after no fertility treatment. After adjustment, children born after ART and OI/IUI had the same prevalence of being overweight (11%; POR 1.00, 95% confidence interval [CI] 0.91 to 1.11; p = 0.95) or obese (1.9%; POR 1.01, 95% CI 0.79 to 1.29; p = 0.94). Comparison of ICSI with conventional IVF yielded similar pattern (POR 0.95, 95% CI 0.83 to 1.07; p = 0.39 for overweight and POR 1.16, 95% CI 0.84 to 1.61; p = 0.36 for obesity). Obesity was more prevalent after frozen-thawed (2.7%) than fresh embryo transfer (1.8%) (POR 1.54, 95% CI 1.09 to 2.17; p = 0.01). The associations between fertility treatments and BMI were only modestly different in subgroups defined by the cause of infertility. Study limitations include potential residual confounding, restriction to live births, and lack of detailed technical information about the IVF procedures. CONCLUSIONS: We found no association with BMI at age 5 to 8 years when comparing ART versus OI/IUI or when comparing ICSI versus conventional IVF. However, use of frozen-thawed embryo transfer was associated with a 1.5-fold increased risk of obesity compared to fresh embryo transfer. Despite an elevated relative risk, the absolute risk difference was low. CI - Copyright: (c) 2023 Laugesen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FAU - Laugesen, Kristina AU - Laugesen K AUID- ORCID: 0000-0001-7971-8223 AD - Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus, Denmark. FAU - Veres, Katalin AU - Veres K AUID- ORCID: 0000-0001-8549-8781 AD - Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus, Denmark. FAU - Hernandez-Diaz, Sonia AU - Hernandez-Diaz S AD - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America. FAU - Chiu, Yu-Han AU - Chiu YH AUID- ORCID: 0000-0002-0904-7855 AD - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America. AD - Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pennsylvania, United States of America. FAU - Oberg, Anna Sara AU - Oberg AS AD - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America. AD - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. FAU - Hsu, John AU - Hsu J AD - Mongan Institute, Massachusetts General Hospital, Boston, Massachusetts, United States of America. AD - Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America. AD - Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts, United States of America. FAU - Rinaudo, Paolo AU - Rinaudo P AUID- ORCID: 0000-0002-6528-6009 AD - Department of Obstetrics Gynecology and Reproductive Sciences, University of California, San Francisco, California, United States of America. FAU - Spaan, Mandy AU - Spaan M AUID- ORCID: 0000-0002-3872-005X AD - Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands. FAU - van Leeuwen, Flora AU - van Leeuwen F AD - Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands. FAU - Sorensen, Henrik Toft AU - Sorensen HT AUID- ORCID: 0000-0003-4299-7040 AD - Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus, Denmark. LA - eng GR - R01 HD088393/HD/NICHD NIH HHS/United States PT - Journal Article DEP - 20231219 PL - United States TA - PLoS Med JT - PLoS medicine JID - 101231360 SB - IM MH - Pregnancy MH - Female MH - Child MH - Male MH - Humans MH - Child, Preschool MH - Cohort Studies MH - *Pediatric Obesity/epidemiology/etiology/therapy MH - Overweight/epidemiology/etiology MH - Semen MH - Reproductive Techniques, Assisted/adverse effects MH - *Infertility/epidemiology/therapy MH - Denmark/epidemiology PMC - PMC10729995 COIS- The authors have declared that no competing interests exist. EDAT- 2023/12/19 19:53 MHDA- 2023/12/21 06:42 PMCR- 2023/12/19 CRDT- 2023/12/19 13:32 PHST- 2023/04/24 00:00 [received] PHST- 2023/11/16 00:00 [accepted] PHST- 2023/12/21 06:42 [medline] PHST- 2023/12/19 19:53 [pubmed] PHST- 2023/12/19 13:32 [entrez] PHST- 2023/12/19 00:00 [pmc-release] AID - PMEDICINE-D-23-01124 [pii] AID - 10.1371/journal.pmed.1004324 [doi] PST - epublish SO - PLoS Med. 2023 Dec 19;20(12):e1004324. doi: 10.1371/journal.pmed.1004324. eCollection 2023 Dec.