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Indicated preterm birth appears to share a number of risk factors with spontaneous preterm birth. In a cohort of more than 2,900 pregnant women, Meis and colleagues (1998) noted a relation between indicated preterm birth and mullerian duct abnormality (OR; 95% CI: 7.02; 1.69-29.15, proteinuria at less than 24 weeks of gestation (OR; 95% CI: 5.85; 2.66-12.89), a history of chronic hypertension (OR; 95% CI: 4.06; 2.29-7.55), a history of indicated preterm birth (OR; 95% CI: 2.79; 1.45-5.40), a history of lung disease (OR; 95% CI: 2.52; 1.32-4.80), previous spontaneous preterm birth (OR; 95% CI: 2.45; 1.55-3.89), age greater than 30 years (OR; 95% CI: 2.42; 1.57-3.74), being African American (OR; 95% CI: 1.56; 1.02-2.40), and working during pregnancy (OR; 95% CI: 1.49; 1.02-2.19). With the possibility of a significant heterogeneity of risk factors and etiologic overlap, studies of preterm birth should consider indicated and spontaneous preterm births both together and separately as outcomes of interest (Savitz et al., 2005).

A number of maternal medical conditions are associated with an increased risk of indicated preterm birth (Table 5-1). Maternal medical illnesses such as chronic hypertension, pre-pregnancy diabetes mellitus, or systemic lupus erythematosus can alter or limit the placental delivery of oxygen and nutrients to the developing fetus, possibly resulting in fetal growth restriction. These same maternal medical illnesses also increase the risk of preeclampsia and, thus, the risk of indicated preterm birth. The mechanism(s) that places a woman at increased risk for preeclampsia is unknown. Acute maternal medical conditions may also result in preterm birth. For example, severe trauma and shock are acute conditions that could create a nonreassur-ing fetal status or placental abruption and thus lead to indicated preterm birth. The progressive course of some medical illnesses could mandate indicated preterm birth to preserve the health and well-being of the mother. Functional or structural maternal cardiac disease is an example of one such illness. Fetal conditions, such as red cell alloimmunization or a twin-to-twin transfusion sequence, might also progress to require indicated preterm birth in an effort to prevent stillbirth.

There is some evidence for a relationship between birth defects and preterm birth. Ras-mussen and colleagues (2001) examined more than 250,000 infants with known gestational ages born between 1989 and 1995 in the Atlanta, Georgia, metropolitan area. Infants born at less than 37 weeks of gestation were more than twice as likely to have a range of birth defects than infants born at term, between 37 and 41 weeks of gestation (RR; 95%CI: 2.43; 2.30-2.56). The risk of preterm birth in infants with birth defects was 21.5 percent, whereas it was 9.3 percent in infants without birth defects. The relationship between preterm birth and birth defects was also analyzed by smaller gestational age categories (20 to 28 weeks, 29 to 32 weeks, 33 to 34 weeks, and 35 to 36 weeks). Compared to infants born at term, the risk of preterm birth was the highest for those born at between 29 and 32 weeks of gestation (RR; 95%CI: 3.37; 3.04-3.73). Similar results were found when the analysis was stratified by maternal age, race, and the infant's gender. Data was not specifically provided on the proportion of births that were spontaneous versus indicated. However, the authors note that while some deliveries of babies with birth defects may have been indicated it is unlikely that these deliveries would have performed among infants in the 29 to 32 week gestational age category, unless survival of the fetus was not anticipated. In another study of 2,761 infants born alive with spina bifida between 1995 and 2001 in selected states, approximately 22 percent were born preterm and accounted for more than half of the deaths of infants with spina bifida (Kirk et al., 2006).

In analyses provided to the Committee from the Utah Birth Defects Prevention Network, between 1999 and 2004, about 20 percent of the infants born alive with birth defects in the state of Utah were born preterm. These results are consistent with those reported by Rasmussen et al. and Kirk et al. It may be that some birth defects increase the risk for preterm birth, that some so-ciodemographic factors that are associated with preterm birth are also associated with some birth defects, or that the two conditions may share other maternal risk factors or medical conditions (Rasmussen et al., 2001). Further investigation is needed to understand this association.

TABLE 5-1 Examples of Maternal Medical Problems That May Lead to Indicated Preterm Birth

Chronic hypertension

Systemic lupus erythematosus

Restrictive lung disease

Hyperthyroidism

Pregestational diabetes mellitus

Maternal cardiac disease

Asthma

Gestational Diabetes Millitus Pre-gestational renal disorders Hypertensive disorders of pregnancy

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