DESCRIPTION (provided by investigator): Infertility affects an estimated 12 percent-15 percent of women of reproductive age. The use of fertility enhancing therapies, including Assisted Reproductive Technologies (ART), has risen steadily in the United States, with an estimated 1 percent-3 percent of births involving ART. Numerous studies have reported significantly higher risks of adverse perinatal outcomes in assisted-versus spontaneous-conception pregnancies. Infertility and sub fertility diagnoses, independent of ART, can also result in higher rates of adverse pregnancy outcomes. Documenting the added effect of ART, beyond underlying sub fertility, on child health outcomes remains a challenge. This applications describes an innovative collaboration between Boston University's School of Public Health, the Massachusetts Department of Public Health, the Society for Assisted Reproductive Technology, and the Centers for Disease Control and Prevention. The collaboration creates a unique longitudinal, population-based, source of data that combines detailed clinical information on ART treatment and infertility diagnoses for the resultant live births and fetal deaths from 2004 through 2011, with the Massachusetts Pregnancy to Early Life Longitudinal (PELL) Data System. PELL contains longitudinal data on pregnancy, births, deaths, hospital utilization, birth defects and public program participation including Early Intervention. The resulting database will track reproductive and child health outcomes to 3 years of age among three groups: babies conceived through ART (~18,000), and those not conceived through ART to subfertile women (~5,000) and those conceived to fertile women (~354,000). This project addresses key limitations of prior ART research (limited subfertility comparison groups, and lack of population-based data and longitudinal child health measures). Two broad hypotheses will be tested: (1) children born from ART treatments are at significantly higher risk of compromised fetal, perinatal, infant, and early childhood health outcomes compared to the two comparison groups, and (2) risk of adverse infant and child health outcomes will vary by ART treatment parameters, infertility diagnoses, and their interaction. The treatment parameters will include source of gametes; state of oocytes or embryos; stage of the embryo; micromanipulation; number of embryos transferred; early fetal loss; and number and outcome of prior treatment cycles. In both cases we will test these hypotheses at three age periods: 1) fetal/perinatal; 2) infant health to one year; and 3) child health to three years. The analyses will proceed in five stages: 1) univariate analyses; 2) unadjusted bivariate analyses; 3) multivariate analyses adjusted for known confounders; 4) subgroup analyses; and 5) path analysis to assess the differential effect of ART treatment parameters and infertility diagnoses, as well as the magnitude of the overall effect of ART, and the direct and indirect effects of plurality on perinatal and child health outcomes in an eight-year, population-based sample. The result will be the largest, most refined analysis ever completed of child health outcomes associated with ART. PUBLIC HEALTH RELEVANCE: Research has shown that children born after infertility and assisted reproductive technology (ART) treatments are at greater risk for adverse health outcomes, although the generalizability of prior studies has been hampered by small sample sizes and the lack of a subfertility comparison group. As the use of infertility treatments continue to rise, it is important to determine how much of this increased risk is related to the ART treatment rather than the underlying infertility, and if there are residual effects extending into early childhood. The proposed project will link ART clinical data from 2004 to 2011 to the Massachusetts Pregnancy to Early Life Longitudinal birth and fetal death file (resulting in approximately 18,000 ART assisted births, 5,000 births with no ART but other subfertility indicators, and 380,000 other births), facilitating the largest and most comprehensive U.S. study to date on infertility, ART and child health from birth to age three.