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Infertility treatment and children's longitudinal growth between birth and 3 years of age.

ABSTRACT: Does early childhood growth from birth through to 3 years of age differ by mode of conception?Findings suggest early childhood growth was comparable for children irrespective of infertility treatment, but twins conceived with ovulation induction with or without intrauterine insemination (OI/IUI) were slightly smaller than twins conceived without treatment.Although studies have found that babies conceived with infertility treatment are born lighter and earlier than infants conceived without treatment, little research especially for non-assisted reproductive technology (ART) treatments has focused on their continued growth during early childhood.Upstate KIDS recruited infants born (2008-2010) to resident upstate New York mothers. Infants were sampled based on birth certificate indication of infertility treatment; specifically, for every singleton conceived by infertility treatment, three singletons without infertility treatment were recruited and matched on region of birth. All multiple births irrespective of treatment were also recruited. Children were prospectively followed, returning questionnaires every 4-6 months until 3 years of age. In total, 3905 singletons, 1129 sets of multiples (96% of whom were twins) enrolled into the study. Analyses included 3440 (88%) singletons (969 conceived with treatment; specifically, 433 with ART and 535 with OI/IUI) and 991 (88%) sets of multiples (439 conceived with treatment; specifically 233 with ART and 206 with OI/IUI) with growth data available.Mothers reported infertility treatment use at baseline and children's height and weight from pediatric visits. Self-reported use of ART was previously verified by linkage with the US Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database. Mixed linear models with cubic splines accounting for age and age-gender interactions were used to estimate mean differences in growth from birth to 3 years by infertility treatment status and adjusting for maternal age, race, education, private insurance, smoking status during pregnancy, maternal pre-pregnancy and paternal body mass indices (BMI).Compared with singletons conceived without treatment (n = 2471), singletons conceived by infertility treatment (433 by assisted reproductive technologies (ART), 535 by OI/IUI and 1 unknown specific type) did not differ in growth. Compared with twins not conceived with treatment (n = 1076), twins conceived with OI/IUI (n = 368) weighed slightly less over follow-up (122 g). They were also proportionally smaller for their length (-0.17 weight-for-length z-score units). No differences in mean size over the 3 years were observed for twins conceived by ART, though some evidence of rapid weight gain from birth to 4 months (adjusted OR 1.08; 95% CI: 1.00-1.16) suggestive of catch up growth was observed.Participants from upstate New York may not be representative of US infants. Although accounted for in statistical analysis, attrition during follow-up may have limited power to detect small differences.This study is the first to prospectively track the growth of children conceived with and without infertility treatment in the USA, including a substantial number of twins. Our findings are similar to what was previously observed in the ART literature outside of the states.Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; contracts #HHSN275201200005C, #HHSN267200700019C). Authors have no competing interests to declare.Not applicable.

SUBMITTER: Yeung EH

PROVIDER: S-EPMC4901884 | biostudies-other | 2016 Jul

REPOSITORIES: biostudies-other

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Infertility treatment and children's longitudinal growth between birth and 3 years of age.

Yeung E H EH Sundaram R R Bell E M EM Druschel C C Kus C C Xie Y Y Buck Louis G M GM

Human reproduction (Oxford, England) 20160510 7

<h4>Study question</h4>Does early childhood growth from birth through to 3 years of age differ by mode of conception?<h4>Summary answer</h4>Findings suggest early childhood growth was comparable for children irrespective of infertility treatment, but twins conceived with ovulation induction with or without intrauterine insemination (OI/IUI) were slightly smaller than twins conceived without treatment.<h4>What is known already</h4>Although studies have found that babies conceived with infertility ...[more]

PMID: 27165624

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Project description:ImportanceDespite the increased perinatal risks associated with pregnancies conceived with infertility treatment, there are no recommendations for timing of delivery among this at-risk population.ObjectiveTo identify the gestational age at which the ongoing risks of stillbirth are optimally balanced with the risks of neonatal comorbidities and infant deaths in term singleton pregnancies conceived with infertility treatment.Design, setting, and participantsThis cohort study used birth and death data from January 1, 2014, to December 31, 2018, in the US obtained from the National Center for Health Statistics. Singleton pregnancies conceived with infertility treatment delivered at term (37-42 weeks' gestation) were eligible for inclusion. The exclusion criteria were deliveries at less than 37 weeks' or at least 43 weeks' gestation and pregnancies with unknown history of infertility treatment, congenital anomalies, pregestational diabetes, pregestational hypertension, gestational hypertension, and preeclampsia. Data were analyzed from July 22, 2022, to June 24, 2023.ExposureGestational age at delivery between 37 and 42 weeks.Main outcomes and measuresThe primary outcome was optimal timing of delivery. To ascertain this timing, the risk of delivery (rate of neonatal morbidity and infant death) at a given gestational week was compared with the risk of delivery in the subsequent week of gestation for an additional week (rate of stillbirth during the given week per 10 000 ongoing pregnancies plus rate of neonatal morbidity and infant death in the subsequent week of gestation per 10 000 deliveries). The rates of stillbirth, neonatal morbidity, and infant death (within 1 year of life) were compared at each week. Neonatal morbidity included an Apgar score of 3 or lower at 5 minutes, requirement of ventilation for 6 hours or more, neonatal intensive care unit admission, and seizures.ResultsOf the 178 448 singleton term pregnancies conceived with infertility treatment (maternal mean [SD] age, 34.2 [5.2] years; mean [SD] gestational age, 39.2 [1.2] weeks; 130 786 [73.5%] were non-Hispanic White patients). The risk of delivery in the subsequent week of gestation was lower than the risk of delivery at both 37 weeks (628 [95% CI, 601-656] vs 1005 [95% CI, 961-1050] per 10 000 live births) and 38 weeks (483 [95% CI, 467-500 vs 625 [95% CI, 598-652] per 10 000 live births). The risks of delivery in subsequent week of gestation significantly exceeded the risk of delivery at 39 weeks (599 [95% CI, 576-622] vs 479 [95% CI, 463-495] per 10 000 live births) and were not significant at 40 weeks (639 [95% CI, 605-675] vs 594 [95% CI, 572-617] per 10 000 live births) and 41 weeks (701 [95% CI, 628-781] vs 633 [95% CI, 599-669] per 10 000 live births).Conclusions and relevanceResults of this study suggest that, in pregnancies conceived with infertility treatment, delivery at 39 weeks provided the lowest perinatal risk when comparing risk of delivery at this week of gestation vs the subsequent week of gestation.

Project description:Study questionIs the use of ART, a proxy for infertility, associated with epigenetic age acceleration?Summary answerThe epigenetic age acceleration measured by Dunedin Pace of Aging methylation (DunedinPoAm) differed significantly between non-ART and ART mothers.What is known alreadyAmong mothers who used ART, epigenetic age acceleration may be associated with low oocyte yield and poor ovarian response. However, the difference in epigenetic age acceleration between non-ART and ART mothers (or even fathers) has not been examined.Study design, size, durationThe Norwegian Mother, Father and Child Cohort Study (MoBa) recruited pregnant women and their partners across Norway at around 18 gestational weeks between 1999 and 2008. Approximately 95 000 mothers, 75 000 fathers and 114 000 children were included. Peripheral blood samples were taken from mothers and fathers at ultrasound appointments or from mothers at childbirth, and umbilical cord blood samples were collected from the newborns at birth.Participants/materials, setting, methodsAmong the MoBa participants, we selected 1000 couples who conceived by coitus and 894 couples who conceived by IVF (n = 525) or ICSI (n = 369). We measured their DNA methylation (DNAm) levels using the Illumina MethylationEPIC array and calculated epigenetic age acceleration. A linear mixed model was used to examine the differences in five different epigenetic age accelerations between non-ART and ART parents.Main results and the role of chanceWe found a significant difference in the epigenetic age acceleration calculated by DunedinPoAm between IVF and non-ART mothers (0.021 years, P-value = 2.89E-06) after adjustment for potential confounders. Further, we detected elevated DunedinPoAm in mothers with tubal factor infertility (0.030 years, P-value = 1.34E-05), ovulation factor (0.023 years, P-value = 0.0018) and unexplained infertility (0.023 years, P-value = 1.39E-04) compared with non-ART mothers. No differences in epigenetic age accelerations between non-ART and ICSI fathers were found. DunedinPoAm also showed stronger associations with smoking, education and parity than the other four epigenetic age accelerations.Limitations, reasons for cautionWe were not able to determine the directionality of the causal pathway between the epigenetic age accelerations and infertility. Since parents' peripheral blood samples were collected after conception, we cannot rule out the possibility that the epigenetic profile of ART mothers was influenced by the ART treatment. Hence, the results should be interpreted with caution, and our results might not be generalizable to non-pregnant women.Wider implications of the findingsA plausible biological mechanism behind the reported association is that IVF mothers could be closer to menopause than non-ART mothers. The pace of decline of the ovarian reserve that eventually leads to menopause varies between females yet, in general, accelerates after the age of 30, and some studies show an increased risk of infertility in females with low ovarian reserve.Study funding/competing interest(s)This study was partly funded by the Research Council of Norway (Women's fertility, project no. 320656) and through its Centres of Excellence Funding Scheme (project no. 262700). M.C.M. has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement number 947684). The authors declare no conflict of interest.Trial registration numberN/A.

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Infertility treatment and children's longitudinal growth between birth and 3 years of age.

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Infertility treatment and children's longitudinal growth between birth and 3 years of age.

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