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

Nutritional Interventions

In developed countries, risk factors for spontaneous preterm birth include being underweight before pregnancy as well as gaining below-average weight during pregnancy.[42] Nutritional status during pregnancy can be described by indicators, such as the BMI, nutritional intake and serum assessments for various analytes.[42,43,44,45] For example, a low pre-pregnancy BMI is associated with a high risk of spontaneous preterm birth, whereas obesity can be protective for this outcome.[42] Women with low serum concentrations of iron, folate or zinc have more preterm births than those with measurements within the normal range.[42,43,44,45] There are many potential mechanisms by which maternal nutritional status might affect preterm birth - for example, spontaneous preterm birth can be related to maternal thinness by decreased blood volume and reduced uterine blood flow. Thin women might also consume fewer vitamins and minerals, low concentrations of which are associated with decreased blood flow and increased maternal infections.[46,47] Obese women are more likely to have infants with congenital anomalies, such as neural-tube defects, and these infants are more likely to be delivered preterm.[48]

To date, nutritional interventions that have been studied include nutritional counseling, caloric supplementation, protein supplementation and vitamin or mineral supplementation. There is a paucity of convincing evidence of nutritional counseling changing eating habits of gravid females, much less the outcome of pregnancy.[43] Data from the US Special Supplementation Program for Women, Infants and Children (WIC), which provides a calorically enriched diet to low-income pregnant women, has demonstrated that caloric supplementation is associated with small increases in birthweight but no decrease in preterm birth. Greater increases in birthweight and reductions in preterm birth are seen with the provision of caloric supplementation in areas of relative famine.[49] Protein supplementation during pregnancy appears to increase adverse pregnancy outcomes including preterm birth.[50]

The association between maternal iron status and its surrogate - iron deficiency anemia - and prematurity is complicated. Owing to the unequal rates of expansion of plasma volume and red cell mass during pregnancy, women in the second or early third trimester routinely have lower hematocrit values than those at term.[51,52,53,54] Failure to correct for gestational age has therefore resulted in a misleading association between anemia and prematurity. Except at the lowest limits of hematocrit levels, studies accounting for gestational age have demonstrated little correlation between anemia and preterm birth. Accordingly, iron supplementation may raise hematocrit levels, but does not consistently change the incidence of preterm birth.[53,54] Low maternal zinc levels have been associated with an increased risk of restricted fetal growth and possibly preterm birth.[55] Several, but not most, trials of zinc supplementation have demonstrated an increase in birthweight, and some, including a previous study of ours,[56,57] suggested that zinc supplementation may reduce the rate of preterm birth, especially among thin women in a low-income minority population of US women with moderately low serum zinc values. Studies of folate supplementation to reduce the rate of preterm birth have also had conflicting results. The Cochrane review of data from ten trials found no overall effect of calcium supplementation on the risk of preterm birth.[58] The efficacy of combined vitamin and mineral supplementation, which is used in many Western countries in attempts to lower the risk of preterm birth has not been rigorously evaluated.[59,60] In inner-city populations, women who used a vitamin-mineral supplement had significantly fewer preterm births than those who did not.[59] However, because this analysis was not derived from a randomized trial, factors other than supplementation, such as self-selection, may have accounted for the observed differences on the outcome of pregnancy. Increased intake of the antioxidant vitamins C and E had no effect on the preterm birth rate in recent large, placebo-controlled trials of these vitamins intended to assess their effect on the rate of pre-eclampsia.[61] Thus, although a few observational studies suggested reduced rates of preterm birth in women taking dietary supplements, in most prospective trials, vitamin or mineral supplementation as well as protein and calorie supplementation had no consistent benefit.

In populations with a high dietary intake of omega-3 polyunsaturated fatty acids (PUFAs), low preterm birth rates have been observed.[62,63] This effect is believed to occur because omega-3 PUFAs reduce levels of proinflammatory cytokines. Dietary supplementation has been associated with reduced production of inflammatory mediators, and a randomized trial of omega-3 supplements conducted in women at risk of preterm birth found a 50% decrease in preterm birth.[64] This has not been confirmed in other populations, and no benefit to PUFAs were observed in a recently completed trial by the NIH Maternal-Fetal Medicine Network.[145]

In summary, women with an adequate nutritional status and a normal BMI have better pregnancy outcomes than other women. Although nutritional interventions in developing countries have promise in improving certain pregnancy outcomes, it remains unclear whether any nutritional intervention is associated with a reduction in the rate of preterm birth.

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