The Association Between High Birth Weight and Long-Term Outcomes—Implications for Assisted Reproductive Technologies: A Systematic Review and Meta-Analysis

Abstract

Background: Studies have shown that the prevalence of children born with high birth weight or large for gestational age (LGA) is increasing. This is true for spontaneous pregnancies; however, children born after frozen embryo transfer (FET) as part of assisted reproductive technology (ART) also have an elevated risk. In recent years, the practice of FET has increased rapidly and while the perinatal and obstetric risks are well-studied, less is known about the long-term health consequences.Objective: The aim of this systematic review was to describe the association between high birth weight and LGA on long-term child outcomes.Data Sources: PubMed, Scopus, and Web of Science were searched up to January 2021. Exposure included high birth weight and LGA. Long-term outcome variables included malignancies, psychiatric disorders, cardiovascular disease, and diabetes.Study Selection: Original studies published in English or Scandinavian languages were included. Studies with a control group were included while studies published as abstracts and case reports were excluded.Data Extraction: The methodological quality, in terms of risk of bias, was assessed by pairs of reviewers. Robins-I (www.methods.cochrane.org) was used for risk of bias assessment in original articles. For systematic reviews, AMSTAR (www.amstar.ca) was used. For certainty of evidence, we used the GRADE system. The systematic review followed PRISMA guidelines. When possible, meta-analyses were performed.Results: The search included 11,767 articles out of which 173 met the inclusion criteria and were included in the qualitative analysis, while 63 were included in quantitative synthesis (meta-analyses). High birth weight and/or LGA was associated with low to moderately elevated risks for certain malignancies in childhood, breast cancer, several psychiatric disorders, hypertension in childhood, and type 1 and 2 diabetes.Conclusions: Although the increased risks for adverse outcome in offspring associated with high birth weight and LGA represent serious health effects in childhood and in adulthood, the size of these effects seems moderate. The identified risk association should, however, be taken into account in decisions concerning fresh and frozen ART cycles and is of general importance in view of the increasing prevalence in high birthweight babies.

Immunoendocrine Dysregulation during Gestational Diabetes Mellitus: The Central Role of the Placenta

“…Finally, fetal programming in GDM has been studied in the context of DOHaD hypothesis (developmental origins of health and disease) to understand the long-term consequences of growing in a hyperglycemic environment during life in utero. Hyperglycemia and maternal obesity generate epigenetic changes in fetal programming, increasing the risk for obesity, T2DM, impaired glucose tolerance, insulin resistance, coronary heart disease, chronic arterial hypertension, dyslipidemia, metabolic syndrome, and some cancers in the future life of the newborn [ 3 , 323 , 324 , 325 , 326 , 327 ]. Interestingly, it has been observed that GDM effects in childhood are manifested after two years of age, such as an increase in BMI and hyperglycemia [ 328 ].…”

Update on the Epigenomic Implication of Embryo Cryopreservation Methods Applied in Assisted Reproductive Technologies With Potential Long-Term Health Effects

“…A large epidemiological study performed by our group using the Swedish population-based registers, compared 43 506 children born after ART vs 2 847 108 naturally conceived children and found a significantly increased risk of infant mortality from birth up to 1 year of life in singletons after ART, specifically when FETs were applied ( Rodriguez-Wallberg et al, 2020 ). High birthweight and large children for gestational age have been associated exclusively with FET in previous European studies ( Magnusson et al, 2021 ; Westvik-Johari et al, 2021 ). All these findings have been identified early in life and the long-term consequences when the ART population becomes older are unknown.…”

Późne rodzicielstwo i rozród wspomagany: analiza ryzyka wystąpienia chorób przewlekłych u potomstwa

“…Dopiero później rozpoczęto dłuższą (6-7-dniową) hodowlę zarodków ludzkich do stadium blastocysty. Zaś, w zeszłym roku doczekaliśmy się szczegółowych opracowań wykazujących, że problem zwiększonej masy płodu i wynikających z tego powikłań pourodzeniowych, ma miejsce również w przypadku wydłużonej hodowli zarodków ludzkich [174,175]. Nasuwa się pytanie: czy można było uniknąć tych problemów u ludzi i nie stosować wydłużonej hodowli zarodków ludzkich w oparciu o wcześniejsze alarmujące wyniki prac na zwierzętach?…”