Infertility treatment and the risk of small for gestational age births: a population-based study in the United States

OBJECTIVE: To evaluate the association between infertility treatments and small for gestational age (SGA) births. DESIGN: Cross-sectional study. SETTING: United States, 2015–2019. PATIENT(S): Women (n = 16,836,228) who delivered nonmalformed, singleton live births (24–44 weeks’ gestation). INTERVENTION(S): Any infertility treatment, including assisted reproductive technology (ART) and prescribed fertility-enhancing medications. MAIN OUTCOME MEASURE(S): Small for gestational age birth, defined as sex-specific birth weight <10% for gestational age. Associations between SGA and infertility treatment were derived from Poisson regression with robust variance. Risk ratios (RR) and 95% confidence intervals (CI) were derived after adjusting for confounders. In a sensitivity analysis, we corrected for nondifferential exposure misclassification and unmeasured confounding biases. RESULT(S): Subsequently, 1.4% (n = 231,177) of pregnancies resulted from infertility treatments (0.8% ART and 0.6% fertility-enhancing medications). Of these, SGA births occurred in 9.4% (n = 21,771) and 11.9% (n = 1,755,925) of pregnancies conceived with infertility treatment and naturally conceived pregnancies, respectively (adjusted RR, 1.07; 95% CI, 1.06, 1.08). However, after correction for misclassification bias and unmeasured confounding, infertility treatment was associated with a 27% reduced risk of SGA (bias-corrected RR, 0.73; 95% CI, 0.53, 0.85). Similar trends were seen for analyses stratified by exposure to ART and fertility-enhancing medications, as well as for SGA <5th and <3rd percentiles. CONCLUSION(S): Exposure to infertility treatment is associated with a reduced risk of SGA births. These findings, which are contrary to some published reports, may reflect changes in the modern practice of infertility care, maternal lifestyle, and compliance with prenatal care within the infertile population. Until these findings are corroborated, the associations must be cautiously interpreted.