Assisted Reproduction and Child Health: Risk of Birth Defects, Mortality, and Effect on Grade School Performance

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It is estimated that about 12% of reproductive age women in the United States have ever sought medical care for infertility. Assisted reproductive technology (ART) includes all infertility treatments to achieve conception; in vitro fertilization (IVF) is the process by which an oocyte is fertilized by semen outside the body; non-IVF ART treatments include ovulation induction, artificial insemination, and intrauterine insemination. In 2013 in the United States, there were nearly 68,000 babies born from IVF, accounting for 1.7% of all births, a proportion which has doubled over the past decade. To date, there has not been a population-based study of ART and IVF in the United States linking data on ART treatments, birth outcomes, registry-confirmed birth defects, and school performance. With this proposed study we seek to fill this knowledge gap. The purpose of this study is to evaluate the risk of mortality, birth defects, and effect on grade school performance among children conceived through IVF and ART, their siblings, and controls in New York, Texas, Massachusetts, and North Carolina. This proposed study will be based on births from 2004-18, and will include an estimated 163,000 IVF children, 41,000 IVF siblings, and 1,250,000 non-IVF control children. Overall Specific Aim: To compare the rates of birth defects and mortality, and effect on school performance among children conceived with IVF, non-IVF ART, and spontaneously, including siblings. Hypothesis 1: Children born from IVF have higher risks for birth defects than the control group; the risk varies by treatments and parental characteristics. Primary Aims:1) To test whether the risk of birth defects in IVF and non-IVF ART births are higher than in spontaneously-conceived births; 2) To identify parental factors affecting risk within each group; 3) In the IVF group, to identify treatment factors that affect the risk. Hypothesis 2: Children born from IVF have higher risks of death compared to their siblings and non-IVF Control children, primarily due to plurality status (greater likelihood of being conceived as a twin, triplet, or quadruplet, but born as a singleton; or of having been born a twin, triplet, or quadruplet) and associated excess of growth restriction (small-for-gestational age) and prematurity. This greater perinatally-related mortality risk is hypothesized to be nonsignificant by two years of age, and varies by infertility treatments and parental factors (particularly reduced with older maternal age at delivery and higher maternal educational status). Hypothesis 3: Children born from IVF have greater risks of poorer educational performance and are more likely to need special education services compared to their siblings and non-IVF Control children, primarily due to their plurality status (greater likelihood of being conceived as a twin, triplet, or quadruplet, but born as a singleton; or of having been born a twin, triplet, or quadruplet) and the associated excess of growth restriction (small-for-gestational age) and prematurity. This greater perinatally-related educational risk varies by infertility treatments and parental factors (particularly reduced with older maternal age at delivery and higher maternal educational status).