Phase 1: Growth and Development
This Study aimed to determine whether infertility treatments, such as ovulation-stimulating medications and various assisted reproductive technologies (ART), adversely affect the growth, motor, and social development of children from birth through age three years, or if these technologies are associated with differences in the timing or rates of infant and child development, including motor and social development, the development of major and, especially, minor neuro-developmental impairments, and with physical growth patterns. Secondarily, but equally important, the Study also aimed to determine to test the American Academy of Pediatrics developmental surveillance and screening algorithm. The Study aimed to provide information to the State of New York Department of Health that will allow it to more effectively plan and implement the New York State Early Intervention Program (EIP) and, by extension, to inform other States' programs nationally.
The Upstate KIDS Study, which represents a collaborative effort among the DIPHR Epidemiology and Biostatistics & Bioinformatics Branches, the New York State Department of Health, and the University at Albany School of Public Health, implemented a matched-exposure cohort design, recruiting infants who were born between 2008 and 2010 in New York State (exclusive of New York City). Using vital records data, all children conceived by infertility treatment and all twins were recruited. In total, approximately 1,300 families whose child(ren) were conceived with infertility treatment (exposed) and approximately 3,700 families whose child(ren) were not conceived with any infertility treatment (unexposed) were recruited. A separate cohort of all higher-order multiples (triplets, quadruplets) were also recruited. Parents completed the infant questionnaires along with the Ages & Stages Questionnaire© developmental screen at 4, 8, 12, 18, 24, 30, and 36 months of chronologic or gestation-corrected age, and the Modified Checklist for Autism in Toddlers at 18 and 24 months. Children who did not pass the screen were referred to the NYS EIP. In a subgroup, residual newborn blood spot samples (punches) from the Guthrie cards were retrieved by the NYS Newborn Screening Program for analysis of inflammatory and immune markers that may indicate an intrauterine infection and be predictive of later disease or delays in development. The Study also conducted linkages to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS), NYS Congenital Malformations Registry, Cancer Registry, Newborn Screening Program, and the EIP, among others.
Phase 2: Cardio-metabolic health
Recent studies have drawn attention to concern that infertility treatment exposure may also increase cardio-metabolic risk. Low birth weight and preterm birth are tied to cardiovascular disease risk and mortality later in adult life. Both adverse birth outcomes are increased among singletons and twins conceived by in vitro fertilization (IVF) and among children conceived techniques apart from ART compared to children conceived naturally. These adverse birth outcomes of children conceived by infertility treatment may serve as an indicator of increased cardio-metabolic risk later in life. Increased risk among those having good birth outcomes, however, cannot be ruled out. The timing of puberty is also of interest, as some pubertal markers appear altered after IVF conception and early adrenarche may confer additional cardio-metabolic risks. Few studies have followed children conceived by non-ART treatment. As such, the cardio-metabolic status of children exposed to infertility treatment inclusive of ART remains unclear.
The Upstate KIDS Follow-Up Study, a collaborative effort among the Epidemiology and Biostatistics & Bioinformatics Branches at NICHD and the University at Albany School of Public Health, will continue the follow-up of approximately 3,200 children from the original cohort through age 8 years primarily by annual questionnaires. A subgroup will be invited to participate in a home/clinic visit program where measurements of cardio-metabolic risk along with biospecimens will be collected from mothers and their children. Lastly, all children will be asked to donate a saliva sample by mail when they reach age 8 years.
For more information on the Upstate KIDS Follow-Up Study, visit www.upstatekidsstudy.org.
- Ma WL, Yun S, Bell EM, Druschel CM, Caggana M, Aldous KM, Buck Louis GM, Kannan K. Temporal trends of polybrominated diphenyl ethers (PBDEs) in the blood of newborns from New York state during 1997 through 2011: analysis of dried blood spots from the newborn screening program. Environmental Science & Technology. 2013; 47(14):8015-8021. PMID: 23755886. PMCID: PMC3725776
- Andersen NJ, Mondal TK, Preissler MT, Freed BM, Stockinger S, Bell E, Druschel C, Louis GM, Lawrence DA. Detection of immunoglobulin isotypes from dried blood spots. Journal of Immunological Methods. 2014; 404:24-32. PMID: 24333851. PMCID: PMC4663688
- Buck Louis GM, Hediger ML, Bell EM, Kus CA, Sundaram R, McLain AC, Yeung E, Hills EA, Thoma ME, Druschel CM. Methodology for Establishing a Population-Based Birth Cohort Focusing on Couple Fertility and Children's Development, the Upstate KIDS Study. Pediatric and Perinatal Epidemiology. 2014; 28(3):191-202. PMID: 24665916. PMCID: PMC4563277
- Ma WL, Gao C, Bell EM, Druschel CM, Caggana M, Aldous KM, Louis GM, Kannan K. Analysis of polychlorinated biphenyls and organochlorine pesticides in archived dried blood spots and its application to track temporal trends of environmental chemicals in newborns. Environmental Research. 2014; 133: 204-210. PMID: 24968082. PMCID: PMC4119526
- Wylie A, Sundaram R, Kus C, Ghassabian A, Yeung EH. Maternal prepregnancy obesity and achievement of infant motor developmental milestones in the Upstate KIDS Study. Obesity (Silver Spring). 2015; 23(4):907-913. PMID: 25755075. PMCID: PMC4380825
- Buck Louis GM, Druschel C, Bell E, Stern JE, Luke B, McLain A, Sundaram R, Yeung E. Use of assisted reproductive technologies treatment as reported by mothers in comparison with registry data: the Upstate KIDS Study. Fertility and Sterility. 2015; 103(6):1461-1468. PMID: 25813287. PMCID: PMC4457573
- Yeung EH, McLain AC, Anderson N, Lawrence D, Boghossian NS, Druschel C, Bell E. Newborn adipokines and birth outcomes. Paediatric and Perinatal Epidemiology. 2015; 29(4):317-325. PMID: 26111443. PMCID: PMC4484786
- Ghassabian A, Sundaram R, Wylie A, Bell E, Bello SC, Yeung E. Maternal medical conditions during pregnancy and gross motor development up to age 24 months in the Upstate KIDS study. Developmental Medicine and Child Neurology. 2015; 58(7):728-734. PMID: 26502927. PMCID: PMC4846588
- Yeung EH, Sundaram R, Bell EM, Druschel C, Kus C, Ghassabian A, Bello S, Xie Y, Buck Louis GM. Examining Infertility Treatment and Early Childhood Development in the Upstate KIDS Study. Journal of the American Medical Association Pediatrics. 2016; 170(3):251-258. PMID: 26746435. PMCID: PMC5000851
- Michels KA, Mumford SL, Sundaram R, Bell EM, Bello SC, Yeung EH. Differences in infant feeding practices by mode of conception among a United States cohort. Fertility and Sterility. 2016; 105(4):1014-1022.e1. PMID: 26773191. PMCID: PMC4821670
- Yeung EH, Sundaram R, Bell EM, Druschel C, Kus C, Xie Y, Buck Louis GM. Infertility treatment and children's longitudinal growth between birth and 3 years of age. Human Reproduction. 2016; 31(7):1621-1628. PMID: 27165624. PMCID: PMC4901884
- Ghassabian A, Sundaram R, Bell E, Bello SC, Kus C, Yeung E. Gross motor milestones and subsequent development. Pediatrics. 2016; 138(1). ppi: e20154372. PMID: 27354457. PMCID: PMC4925077
- Stern JE, McLain AC, Buck Louis GM, Luke B, Yeung EH. Accuracy of self-reported survey data on assisted reproductive technology treatment parameters and reproductive history. American Journal of Obstetrics and Gynecology. 2016; 215(2):219.e1-6. PMID: 26875948. PMCID: PMC4967378
- Yeung EH, Louis GB, Lawrence D, Kannan K, McLain AC, Caggana M, Druschel C, Bell E. Eliciting parental support for the use of newborn blood spots for pediatric research. BioMed Central Medical Research Methodology. 2016; 16:14. PMID: 26846420. PMCID: PMC4741027
- Michels KA, Kim K, Yeung EH, Plowden TC, Chaljub EN, Lu YL, Mumford SL. Adjusting for abstinence time in semen analyses: some considerations. Andrology. 2017; 5(1):191-193. PMID: 27860459. PMCID: PMC5164957
- Broadney MM, Chahal N, Michels KA, McLain AC, Ghassabian A, Lawrence DA, Yeung EH. Impact of Parental Obesity on Neonatal Markers of Inflammation and Immune Response. International Journal of Obesity. 2017; 41(1):30-37. PMID: 27780976. PMCID: PMC5209273
- Yeung EH, Sundaram R, Ghassabian A, Xie Y, Buck Louis G. Parental Obesity and Early Childhood Development. Pediatrics. 2017; 139(2). pii: e20161459. PMID: 28044047. PMCID: PMC5260147
- Robledo CA, Yeung EH, Mendola P, Sundaram R, Boghossian NS, Bell EM, Druschel C. Examining the prevalence rates of preexisting maternal medical conditions and pregnancy complications by source: evidence to inform maternal and child research. Maternal and Child Health Journal. 2017; 21(4):852-862. PMID: 27549105. PMCID: PMC5322241
- Ghassabian A, Sundaram R, Chahal N, McClain AC, Bell E, Lawrence DA, Yeung EH. Determinants of neonatal brain-derived neurotrophic factor and association with child development. Development and Psychopathology. 2017; 29(4):1499-1511. PMID: 28462726
- Boghossian NS, Mendola P, Liu A, Robledo C, Yeung EH. Maternal Serum Markers of Lipid Metabolism in Relation to Neonatal Anthropometry. Journal of Perinatology. 2017; 37(6):629-635. PMID: 28333159. PMCID: PMC5446273
- Mendola P, Ghassabian A, Mills JL, Zhang C, Tsai MY, Liu A, Yeung EH. Retinol-binding protein 4 and lipids prospectively measured during early to mid-pregnancy in relation to preeclampsia and preterm birth risk. American Journal of Hypertension. 2017; 30(6):569-576. PMID: 28338737. PMCID: PMC5861563
- Chahal N, McLain AC, Ghassabian A, Michels KA, Bell EM, Lawrence DA, Yeung EH. Maternal Smoking and Newborn Cytokine and Immunoglobulin Levels. Nicotine & Tobacco Research. 2017; 19(7):789-796. PMID: 28011791. PMCID: PMC5939663
- Vollet K, Ghassabian A, Sundaram R, Chahal N, Yeung EH. Prenatal Fish Oil Supplementation and Early Childhood Development in the Upstate KIDS Study. Journal of Developmental Origins of Health and Disease. 2017; 8(4):465-473. PMID: 28434427. PMCID: PMC5588657
- Liu D, Yeung EH, McLain AC, Xie Y, Buck Louis GM, Sundaram R. A two-step approach for analysis of nonignorable missing outcomes in longitudinal regression: an application to Upstate KIDS Study. Paediatric and Perinatal Epidemiology. 2017; 31(5):468-478. PMID: 28767145. PMCID: PMC5610633
- Michels KA, Ghassabian A, Mumford SL, Sundaram R, Bell EM, Bello SC, Yeung EH. Breastfeeding and motor development in term and preterm infants in a longitudinal US cohort. The American Journal of Clinical Nutrition. 2017; 106(6):1456-1462. PMID: 29092884. PMCID: PMC5698835
- Park H, Sundaram R, Gilman SE, Bell G, Louis GMB, Yeung EH. Timing of Maternal Depression and Sex-Specific Child Growth, the Upstate KIDS Study. Obesity. 2018; 26(1):160-166. PMID: 29090856. PMCID: PMC5739947
- Buck Louis G, Bell E, Xie Y, Sundaram R, Yeung E. Parental Health Status and Infant Outcomes: Upstate KIDS Study. Fertility and Sterility. 2018; 109(2):315-323. PMID: 29338856