ORIGINAL RESEARCH Perinatal Outcome Among Singleton Infants Conceived Through Assisted Reproductive Technology in the United States Laura A. Schieve, PhD, Cynthia Ferre, MS, Herbert B. Peterson, MD, Maurizio Macaluso, MD, Meredith A. Reynolds, PhD, and Victoria C. Wright, MPH OBJECTIVE: To examine perinatal outcome among single- ton infants conceived with assisted reproductive technology (ART) in the United States. METHODS: Subjects were 62,551 infants born after ART treatments performed in 1996 –2000. Secular trends in low birth weight (LBW), very low birth weight (VLBW), pre- term delivery, preterm LBW, and term LBW were exam- ined. Detailed analyses were performed for 6,377 infants conceived in 2000. Observed numbers were compared with expected using a reference population from the 2000 U.S. natality file. Adjusted risk ratios were calculated. RESULTS: The proportion of ART singletons born LBW, VLBW, and term LBW decreased from 1996 to 2000. The proportion delivered preterm and preterm LBW remained stable. After adjustment for maternal age, parity, and race/ ethnicity, singleton infants born after ART in 2000 had ele- vated risks for all outcomes in comparison with the general population of U.S. singletons: LBW standardized risk ratio 1.62 (95% confidence interval 1.49, 1.75), VLBW 1.79 (1.45, 2.12), preterm delivery 1.41 (1.32, 1.51), preterm LBW 1.74 (1.57, 1.90), and term LBW 1.39 (1.19, 1.59). Risk ratios for each outcome remained elevated after restriction to pregnan- cies with only 1 fetal heart or any of 7 other categories: parental infertility diagnosis of male factor, infertility diagno- sis of tubal factor, conception using in vitro fertilization with- out intracytoplasmic sperm injection or assisted hatching, conception with intracytoplasmic sperm injection, conception in a treatment with extra embryos available, embryo culture for 3 days, and embryo culture for 5 days. CONCLUSION: Singletons born after ART remain at in- creased risk for adverse perinatal outcomes; however, risk for term LBW declined from 1996 to 2000, whereas pre- term LBW was stable. (Obstet Gynecol 2004;103: 1144 –53. © 2004 by The American College of Obstetri- cians and Gynecologists.) LEVEL OF EVIDENCE: III In the United States and worldwide, assisted reproduc- tive technologies (ARTs) are increasingly used to over- come infertility. 1 In 2000, close to 100,000 procedures were performed in the United States, resulting in more than 35,000 infants, nearly 1% of the U.S. birth cohort. 1 Although ART is thus providing benefits to thousands of couples, adverse outcomes associated with these proce- dures have been reported. In addition to the known risk for multiple gestation and multiple birth resulting from high-order embryo transfer, recent studies also suggest that singleton infants may be at increased risk for ad- verse outcome compared with naturally conceived sin- gleton infants. A series of studies reported that singletons conceived through ART are at increased risk for low birth weight (LBW), very low birth weight (VLBW), preterm delivery, and fetal growth restriction. 2–13 We recently reported increased risks for LBW and VLBW among singletons recorded in the U.S. popula- tion-based registry of ART procedures maintained by the Centers for Disease Control and Prevention (CDC). Our analysis included more than 18,000 infants con- ceived with ART in 1996 and 1997. 2 We found an increased risk for LBW and VLBW among ART single- tons compared with the general U.S. population of sin- gletons. The risks remained elevated after restricting analyses to subgroups conceived with presumably healthy gametes or carried by a presumably healthy woman, suggesting that the increased risks were, at least in part, due to a treatment effect. Recent evidence from Finland suggests that the risk for LBW and preterm delivery among ART infants may From the Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia; and Division of Reproductive Health and Research, World Health Organization, Geneva, Switzerland. The data used for this study were collected with the assisted reproductive technology reporting system of the Society for Assisted Reproductive Technology. Since 1995, data from this system have been used by the Centers for Disease Control and Prevention (CDC) to calculate pregnancy success rates for assisted reproductive technology clinics operating in the United States. This system is jointly supported by Society for Assisted Reproductive Technology, the American Society for Reproductive Medicine (ASRM), and CDC. We thank the Society for Assisted Reproductive Technology and ASRM, without whose contributions this work would not have been possible. VOL. 103, NO. 6, JUNE 2004 1144 © 2004 by The American College of Obstetricians and Gynecologists. 0029-7844/04/$30.00 Published by Lippincott Williams & Wilkins. doi:10.1097/01.AOG.0000127037.12652.76