Prevention of Preterm Birth

Jeffrey M. Denney; Jennifer F. Culhane; Robert L. Goldenberg

Disclosures

Women's Health. 2008;4(6):625-638. 

In This Article

Behavioral Modification

Mothers experiencing high levels of psychological or social stress have been found in many studies to be at increased risk of preterm birth (generally less than twofold) even after adjustment for the effects of sociodemographic, medical and behavioral risk factors.[114] Furthermore, exposure to objectively stressful conditions, such as housing instability and severe material hardship, has also been associated with preterm birth. The mechanism underlying the association between psychological or social stress and increased risk of preterm birth is unknown. Clinical depression during pregnancy has been reported in up to 16% of women, with up to 35% having some depressive symptoms.[115] Although the results are inconsistent, several reports suggest a relationship (risks generally rose less than twofold) between depression and preterm birth.[116,117] Depression is associated with an increase in smoking and drug and alcohol use; therefore, the relationship between depression and preterm birth might be mediated by these behaviors. Nevertheless, in some studies that adjusted for smoking and drug and alcohol use, the association between depression and preterm birth remained. To date, there is little evidence that any intervention reduces preterm birth in women diagnosed with stress, anxiety or depression. Various trials of social support and counseling have not produced consistently positive results.

Tobacco use increases the risk of preterm birth (less than twofold) after adjustment for other factors.[118,119] The mechanism(s) by which smoking is related to preterm birth has not been elucidated. There are thousands of chemical agents in cigarette smoke of which the in vivo effects of most are not clear. However, both nicotine and carbon monoxide are powerful vasoconstrictors, which have been shown to correlate with placental damage and suboptimal uteroplacental blood flow; these effects lead to fetal growth restriction and, consequently, indicated preterm deliveries; for example, abruption and intrauterine growth restriction. Smoking is also associated with a systemic inflammatory response and may increase spontaneous preterm birth via triggering inflammatory pathways leading to labor. Heavy alcohol consumption - defined as the equivalent of seven alcoholic beverages daily - correlates with preterm birth.[120] Cocaine and heroin use have been associated with preterm birth in several studies. Programs for cessation of tobacco, drug and alcohol use have been recommended as part of a strategy to reduce preterm births. However, the use of these substances is more closely linked to restricted fetal growth than to preterm birth. Moreover, these programs all achieve, at best, relatively low rates of cessation; thus, it is not likely that these interventions will have a substantial impact on preterm birth.[121,122,123]

Substantial progress has been made in understanding the relationship between maternal intrauterine infection and preterm birth.[15,124,125,126,127,128,129] Microbiological studies suggest that intrauterine infection might account for 25-40% of preterm births; however, this might be a minimum estimate because at least several types of intrauterine infection are difficult to detect with conventional culture techniques. Intrauterine infection can be confined to the decidua, extend to the space between the amnion and chorion and reach the amniotic cavity and the fetus. Bacteria in the membranes and an associated inflammatory response in the amniotic fluid have been identified in more than 80% of women in early preterm labor with intact membranes who underwent cesarean section. In spite of these findings, most trials of antibiotic therapy in women with preterm labor have failed to prevent premature birth.[15] It is unknown whether this failure is due to the selection of inappropriate antibiotics, the initiation of treatment too late in the cascade of events leading to spontaneous preterm delivery or other factors.

Bacterial vaginosis, a polymicrobial overgrowth of predominantly anaerobic bacteria, has been consistently associated with a risk of spontaneous preterm birth that is increased by a factor of 1.5-3.[15,130] Furthermore, in several randomized trials involving women at high risk for preterm birth (predominantly because of prior preterm birth), treatment of bacterial vaginosis with metronidazole either alone or in combination with erythromycin resulted in substantial reductions in rates of spontaneous preterm birth.[131] How attributable such results are to gravidas at lower risk remains to be established. However, since so many premature births are related to infection, antibiotic treatment has promise in reducing early spontaneous preterm births, especially among Black women, who have significantly higher rates of bacterial vaginosis compared with other women (30 vs 10%, respectively).[132] Furthermore, recent evidence suggests that treatment of abnormal vaginal flora with either oral or topical clindamycin may have efficacy in reducing preterm birth.[133,134,135]

A 2007 Cochrane review of 15 trials concluded that although antimicrobial treatment can reduce the incidence of bacterial vaginosis in pregnancy, it does not reduce the risk of preterm birth or preterm membrane rupture before 37 weeks for all women or in women with a prior preterm birth.[136] However, the reviewers noted evidence that treatment before 20 weeks' gestation may reduce the risk of preterm birth. One potential reason for the failure of antibiotics to reduce preterm birth is that they may not effectively prevent or treat chorioamnionitis.

Nearly four decades ago, antibiotic treatment for asymptomatic urinary tract infections (UTIs) was found to result in fewer spontaneous preterm deliveries in comparison with untreated UTIs.[137,138] Both symptomatic and asymptomatic UTIs have been associated with an increased risk of preterm delivery, and several randomized trials have provided confirmation that treating asymptomatic bacteriuria not only reduces the risk of maternal pyelonephritis, but may also reduce the risk of preterm birth.

Identification of other infections that may have a causal role in spontaneous preterm birth is the focus of much current research. For example, nearly every sexually transmitted disease has been associated with increased preterm births.[139] However, women with sexually transmitted diseases often have other risk factors for preterm birth, which have rarely been evaluated as confounding factors. Owing to the inconsistency of the association between infection and preterm birth and the relatively low prevalence of most infections, their elimination in pregnant women, although otherwise beneficial, is not likely to have a major effect on the overall rate of preterm birth.

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