Risk of low or very low birth weight rises after assisted reproduction. (Digests).

Infants conceived with the use of assisted reproductive technology (ART) are more likely than infants in the general population to have low or very low birth weight, a large population-based study reveals. (1) The increased prevalence of low or very low birth weight among babies conceived using procedures in which eggs and sperm are handled outside the body (including embryo transfer) can be partially explained by the relatively high proportion of multiple births resulting from these procedures. An additional factor, however, is that singletons conceived through these techniques have almost a doubled risk of having low or very low birth weight, even if they were the only fetus present during pregnancy.

By obtaining data reported to the Centers for Disease Control and Prevention by institutions that had treated infertility with ART, researchers were able to study nearly all such procedures performed in the United States between 1996 and 1997 for women aged 20-60. They identified 42,463 infants born alive who were conceived through a total of 136,972 ART procedures, and they analyzed the prevalence of low birth weight (2,500 g or less) and very low birth weight (less than 1,500 g), as well as factors such as the woman's age, number of previous births, type of ART used, whether ART had been used before and cause of infertility. The researchers calculated expected numbers of infants with low and very low birth weight from data on 3.4 million infants in the general population born in 1997 to women aged 20 or older. The expected numbers were adjusted for maternal age and number of previous births, and were used to estimate standard risk ratios for low and very low birth weight.

Compared with the whole group of women who had used ART, women who gave birth to live infants were more likely to be younger than 35, to have had previous deliveries, to have used fresh (rather than frozen) embryos and not to have used ART before--characteristics linked to higher ART success rates. Singletons and babies from twin births each accounted for 43% of infants conceived by ART. Twelve percent of infants were from triplet births, and the remainder were from births of four or more babies. The proportion of infants who had low birth weight increased from 13% among singletons to 55% among twins, 92% among triplets and nearly 100% among infants from births of four or more babies. The rate of low birth weight was higher among singletons if ultrasound scanning during early pregnancy had detected more than one fetal heart (18-50%) and among twins if scanning had detected more than two fetal hearts (61-90%). Furthermore, the proportion of very-low-birth-weight infants increased with the number of babies per delivery, ranging from 3% among singletons to 67% among infants from births of four or more babies.

The numbers of singletons conceived with ART who had low and very low birth weight were nearly twice the predicted numbers (risk ratio, 1.8 for each). When the singletons were categorized by whether they were born at term (at least 37 weeks' gestation) or preterm, the risk of low birth weight was again elevated for both groups--2.6 and 1.4, respectively. The risk of low birth weight at term remained elevated when analyses were limited to pregnancies during which the ultrasound scan showed one fetal heart (2.6), procedures that used donated eggs and healthy sperm (1.9), cases of paternal infertility (2.9) and surrogate births (1.7). In contrast, preterm singletons conceived with ART had moderately elevated risks of low birth weight if one fetal heart had been detected during pregnancy (1.3) or if donated eggs and healthy sperm were used (1.5). Twins conceived through ART were no more likely than those in the general population to have low birth weight, whether they were delivered at term or earlier.

The authors estimate that conception using ART accounted for fewer than 1% of all infants born in 1997 to women aged 20 or older, but for 3-4% Of those with low or very low birth weight. They note that although the use of ART results in a higher rate of multiple birth, which carries a high risk of low birth weight, ART itself does not seem to increase that risk. However, because singletons conceived by this technology--even if they were born at term and the pregnancy had involved a single fetus-have an increased risk of low birth weight, the investigators conclude that "infants from both singleton and multiple births must be considered in assessing the effect of assisted reproductive technology on the rate of low birth weight in the United States."

REFERENCE

(1.) Schieve LA et al., Low and very low birth weight in infants conceived with use of assisted reproductive technology, New England Journal of Medicine, 2002, 346(10): 731-737.