Maternal selenium status during early gestation and risk for preterm birth

Background

Preterm birth occurs in 5%–13% of pregnancies. It is a leading cause of perinatal mortality and morbidity and has adverse long-term consequences for the health of the child. Because of the role selenium plays in attenuating inflammation, and because low concentrations of selenium have been found in women with preeclampsia, we hypothesized that low maternal selenium status during early gestation would increase the risk of preterm birth.

Methods

White Dutch women with a singleton pregnancy (n = 1197) were followed prospectively from 12 weeks’ gestation. Women with thyroid disease or type 1 diabetes were excluded. At delivery, 1129 women had complete birth-outcome data. Serum concentrations of selenium were measured during the 12th week of pregnancy. Deliveries were classified as preterm or term, and preterm births were subcategorized as iatrogenic, spontaneous or the result of premature rupture of the membranes.

Results

Of the 60 women (5.3%) who had a preterm birth, 21 had premature rupture of the membranes and 13 had preeclampsia. The serum selenium concentration at 12 weeks’ gestation was significantly lower among women who had a preterm birth than among those who delivered at term (mean 0.96 standard deviation (SD) 0.14] μmol/L v. 1.02 SD 0.13] μmol/L; t = 2.9, p = 0.001). Women were grouped by quartile of serum selenium concentration at 12 weeks’ gestation. The number of women who had a preterm birth significantly differed by quartile (χ² = 8.01, 3 degrees of freedom], p < 0.05). Women in the lowest quartile of serum selenium had twice the risk of preterm birth as women in the upper three quartiles, even after adjustment for the occurrence of preeclampsia (adjusted odds ratio 2.18, 95% confidence interval 1.25–3.77).

Interpretation

Having low serum selenium at the end of the first trimester was related to preterm birth and was independent of the mother having preeclampsia. Low maternal selenium status during early gestation may increase the risk of preterm premature rupture of the membranes, which is a major cause of preterm birth.Preterm birth occurs in 5%–13% of pregnancies and is a major public health concern worldwide.¹ Preterm birth, defined as delivery before 37 weeks’ gestation, is the leading cause of perinatal mortality and morbidity.² Short- and long-term consequences to the health of the child include cerebral palsy, respiratory distress syndrome, neurodevelopmental impairment, learning difficulties and behavioural problems.² Despite substantial efforts to explain the mechanisms involved, the incidence of preterm birth is on the rise. For example, in the United States, the incidence increased from 9.5% in 1981 to 12.7% in 2005.¹ Consequently, it is important to identify factors that may contribute to preterm birth, particularly those factors that are preventable.Maternal risk factors for preterm birth include a previous preterm delivery, black race, low socioeconomic status, poor nutrition or becoming pregnant soon after a previous delivery.¹ Risk factors for preterm birth during gestation include multiple-gestation pregnancy and an intrauterine infection that triggers an inflammatory response.^1,3 Endocrine conditions such as diabetes and dysfunction of the thyroid have also been associated with preterm birth, sometimes linked to preterm premature rupture of the membranes.^4,5The trace mineral selenium, available from food (though to a greater or lesser extent according to region), can interact with a number of these risk factors.^6–9 It has been implicated in pregnancy outcome,^9–12 and it plays a role in the immune response and the body’s resistance to infection.⁶ Enzymes containing the mineral, selenoenzymes, can attenuate the excessive inflammatory response associated with adverse pregnancy outcomes, downregulating the expression of pro-inflammatory genes.^6–8 A polymorphism in the gene encoding the selenoprotein SEPS1 has been shown to affect the risk of preeclampsia, a condition that has a strong inflammatory component that is an important cause of preterm birth.⁸ In addition, low selenium status has been identified in women with preeclampsia.¹²We hypothesized that low maternal selenium status (as measured by low serum selenium concentration early in gestation would be associated with preterm birth. Previous small studies have compared plasma selenium and plasma/erythrocyte glutathione peroxidase in mothers and their babies during both term and preterm deliveries. Although lower values have often been found in mothers who had their babies preterm than in mothers who had their babies at term, the findings were inconsistent.^13–15 We did a prospective study to assess selenium status in a large cohort of pregnant women who were followed from early gestation to delivery.