ObjectiveTo test the hypothesis of an association between maternal infertility therapy and the risk of very low birth weight (VLBW), defined as birth weight less than 1500 & independent of the risk of multiple births, and to estimate the contribution of infertility therapy to the national incidence of VLBW.MethodsThe national Maternal and Infant Health Survey conducted in 1988 was used to develop statistics describing outcomes among this birth cohort and to construct logistic regression models evaluating fertility therapy as an independent risk factor for VLBW.ResultsAn estimated 10.1% of live births and 18.2% of VLBW births nationally were associated with either maternal subfertility or infertility therapy (6.8% and 11.4%, respectively). The risk of VLBW among women concerned with subfertility (ie, receiving diagnostic testing or advice on timing intercourse) was 1.4 (95% confidence interval [CI] 1.1, 1.9), whereas that for women undergoing therapeutic interventions (ie, ovarian stimulation, surgery, in vitro fertilization, or artificial insemination) was 2.6 (95% CI 2.1, 3.2). Accounting for effects of multiple gestation, maternal age, and a history of miscarriage, the odds ratios for the concerned and therapy groups were 1.5 (95% CI 1.1, 1.9) and 2.0 (95% CI 1.5, 2.5), respectively. Black women were less likely to use fertility therapy but more likely to experience a therapy-related VLBW.ConclusionFertility therapy is associated with an important portion of all VLBW and with an elevated risk of VLBW, related only in part to an increased risk of multiple gestations. Women expressing concern about subfertility but not receiving therapy are also at increased risk of VLBW, suggesting that a history of infertility may mediate part of the risk associated with fertility therapy.