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Objective: To evaluate whether children conceived using assisted reproductive technology (ART) or ovulation induction (OI) have greater cardiometabolic risk than children conceived without treatment.Design: Clinical assessments in 2018-2019 in the Upstate KIDS cohort.Setting: Clinical sites in New York.Patient(s): Three hundred thirty-three singletons and 226 twins from 448 families.Intervention(s): Mothers reported their use of fertility treatment and its specific type at baseline and approximately 4 months after delivery. High validity of the self-reported use of ART was previously confirmed. The children were followed up from infancy through 8-10 years of age. A subgroup was invited to participate in clinic visits.Main Outcome Measure(s): The measurements of blood pressure (BP), arterial stiffness using pulse wave velocity, anthropometric measures, and body fat using bioelectrical impedance analysis were performed (n = 559). The levels of plasma lipids, C-reactive protein, and hemoglobin A1c were measured using blood samples obtained from 263 children.Result(s): The average age of the children was 9.4 years at the time of the clinic visits Approximately 39% were conceived using fertility treatment (18% using ART and 21% using OI). Singletons conceived using fertility treatment (any type or using ART or OI specifically) did not statistically differ in systolic or diastolic BP, heart rate, or pulse wave velocity. Singletons conceived using OI were smaller than singletons conceived without treatment, but the average body mass index of the latter was higher (z-score: 0.41 [SD, 1.24]) than the national norms. Twins conceived using either treatment had lower BP than twins conceived without treatment. However, twins conceived using OI had significantly higher arterial stiffness (0.59; 95% CI, 0.03-1.15 m/s), which was attenuated after accounting for maternal BP (0.29; 95% CI, -0.03 to 0.46 m/s). Twins did not significantly differ in size or fat measures across the groups. The mode of conception was not associated with the levels of lipids, C-reactive protein, or glycosylated hemoglobin.Conclusion(s): Clinical measures at the age of 9 years did not indicate greater cardiometabolic risk in children conceived using ART or OI compared with that in children conceived without treatment.Clinical Trial Registration Number: ClinicalTrials.gov #NCT03106493. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether deoxyribonucleic acid (DNA) methylation at birth and in childhood differ by conception using assisted reproductive technologies (ART) or ovulation induction compared with those in children conceived without fertility treatment.Design: Upstate KIDS is a matched exposure cohort which oversampled on newborns conceived by treatment.Setting: New York State (excluding New York City).Patient(s): This analysis included 855 newborns and 152 children at approximately 9 years of age.Intervention(s): None.Main Outcome Measure(s): DNA methylation levels were measured using the Illumina EPIC platform. Single CpG and regional analyses at imprinting genes were conducted.Result(s): Compared to no fertility treatment, ART was associated with lower mean DNA methylation levels at birth in 11 CpGs (located in/near SYCE1, SPRN, KIAA2013, MYO1D, GET1/WRB-SH4BGR, IGF1R, SORD, NECAB3/ACTL10, and GET1) and higher mean methylation level in 1 CpG (KLK4; all false discovery rate P<.05). The strongest association (cg17676129) was located at SYCE1, which codes for a synaptonemal complex that plays a role in meiosis and therefore infertility. This CpG remained associated with newborn hypomethylation when the analysis was limited to those conceived with ICSI, but this may be because of underlying male infertility. In addition, nine regions in maternally imprinted genes (IGF1R, PPIEL, SVOPL GNAS, L3MBTL, BLCAP, HYMAI/PLAGL1, SNU13, and MEST) were observed to have decreased mean DNA methylation levels among newborns conceived by ART. In childhood, hypomethylation of the maternally imprinted gene, GNAS, persisted. No CpGs or regions were associated with ovulation induction.Conclusion(s): ART but not ovulation induction was associated with hypomethylation at birth, but only one difference at an imprinting region appeared to persist in childhood. [ABSTRACT FROM AUTHOR]

The cardiometabolic health of children conceived by assisted reproductive technologies (ART) compared with children conceived without medical assistance is unclear. Although the majority of published studies evaluating height, weight, and body mass index have not found differences by method of conception, some studies have indicated differences in adiposity by more direct measures such as skinfolds and dual X-ray absorptiometry. Far fewer studies have investigated other cardiometabolic characteristics, such as blood pressure and measures of lipid and glucose metabolism. Of these studies, some indications of increased blood pressure and recent findings of vascular dysfunction among children conceived by ART compared with children conceived without ART warrant further investigation. Epigenetic differences may be the global mechanism at work, resulting from different aspects of ART treatment, such as ovarian stimulation, in vitro culture, and manipulation of sperm, among other considerations. Fetal growth and placental development may serve as mediators of these effects. Future studies should consider recruiting sufficient numbers of ART and non-ART conceived multiples and collect information on indicators of cardiometabolic health in the parents. Despite some advantages of sibling cohorts in developmental origins research, its feasibility and utility for investigating health of children conceived by ART remains debatable. [ABSTRACT FROM AUTHOR]

Objective: To study the associations between maternal polycystic ovary syndrome (PCOS) and hirsutism with offspring attention-deficit/hyperactivity disorder (ADHD), anxiety, conduct disorder, and behavioral problems.Design: Prospective birth cohort study.Setting: Not applicable.Patient(s): A total of 1,915 mother-child dyads.Intervention(s): None.Main Outcome Measure(s): Maternal report of offspring ADHD, anxiety, or conduct disorder diagnosis at 7 to 8 years; emotional symptoms, behavioral problems (including peer relationship, conduct, hyperactivity/inattention), and prosocial problems measured with the Strengths and Difficulties Questionnaire (SDQ) at 7 years.Result(s): Prevalence of PCOS and hirsutism were 12.0% and 3.9%; 84% of women with hirsutism had PCOS. After adjustment for sociodemographic covariates, prepregnancy body mass index, and parental history of affective disorders, children born to mothers with PCOS had higher risk of anxiety (adjusted risk ratio [aRR] 1.62; 95% confidence interval [CI], 1.02-2.57) and borderline emotional symptoms (aRR 1.66; 95% CI, 1.18-2.33) compared with children born to mothers without PCOS. The associations between maternal PCOS and offspring ADHD were positive but imprecise. Maternal hirsutism was related to a higher risk of children's ADHD (aRR 2.33; 95% CI, 1.28-4.24), conduct disorder (aRR 2.54; 95% CI 1.18-5.47), borderline emotional symptoms, peer relationship problems, and conduct problems (aRRs 2.61; 95% CI, 1.69-4.05; 1.92; 95% CI, 1.16-3.17; and 2.22; 95% CI, 1.30-3.79, respectively).Conclusion(s): Maternal PCOS was associated with offspring anxiety, and hirsutism was related to other offspring behavioral problems. These findings should be interpreted with caution as replication is needed in prospective cohort studies that assess PCOS and hirsutism diagnoses using medical records. [ABSTRACT FROM AUTHOR]

Objective: To assess the association of total isoflavone intake with ovulatory function, including sporadic anovulation in healthy premenopausal women. Design: Prospective cohort study. Setting: University. Patient(s): Participants included 259 healthy regularly menstruating women aged 18–44 years. Intervention(s): None. Main Outcome Measure(s): Serum concentrations of E2, free E2, P, LH, FSH, and SHBG and sporadic anovulation in healthy premenopausal women. Result(s): Isoflavone intake was not associated with E2, free E2, P, LH, and FSH concentrations. Consumption in the highest quartile (Q4: 1.6–78.8 mg/d) was significantly associated with greater SHBG concentrations (β = 0.09; 95% confidence interval [CI] 0.02–0.16), compared with the first quartile (Q1: 0.0–0.3 mg/d). Conclusion(s): Isoflavone intake was not associated with sporadic anovulation (Q4 vs. Q1: odds ratio 0.87, 95% CI 0.32–1.66). Dietary isoflavone intake among young premenopausal women was not related to sex hormone concentrations or anovulation, but was associated with minimally increased SHBG concentrations. These results suggest potential endocrine effects with no subsequent effects on ovulation, easing concerns regarding their impacts on fertility. [Copyright &y& Elsevier]

Objective: To identify associations between fertility treatment use (assisted reproductive technologies, ovulation induction, and artificial insemination) and subsequent infant feeding practices.Design: The Upstate KIDS population-based cohort enrolled mothers who delivered live births in New York (2008-2010), sampling on fertility treatment and plurality.Setting: Not applicable.Patient(s): Data regarding singletons and one randomly selected infant between twins were used.Intervention(s): Not applicable.Main Outcome Measure(s): Mothers reported breast feeding and formula feeding practices at 4, 8, and 12 months postpartum. Modified Poisson regression was used to compare risks for feeding practices by mode of conception. Marginal structural models were used to estimate the controlled direct effects of fertility treatment on feeding, independent of preterm birth.Result(s): Among 4,591 mothers, 1,361 (30%) conceived with the use of fertility treatments. Mothers who used fertility treatments were less likely to breast feed to 12 months after birth and were more likely to provide formula, solids, and juice by 4 months than mothers who did not conceive with treatments. Fertility treatment remained associated with breast feeding cessation and formula feeding in mediation analyses, suggesting that preterm birth does not fully explain these associations.Conclusion(s): Women who conceived with the use of fertility treatments were less likely to breast feed later in infancy and were more likely to provide formula, solids, and juice earlier in infancy. Our analyses accounted for confounding and preterm birth, but other contributing factors may include difficulties feeding twins or workplace breast feeding accommodations. [ABSTRACT FROM AUTHOR]