Interleukin-1 Receptor Antagonist Polymorphism and Birth Timing: Pathway Analysis Among African American Women

Background: Timing of birth is a major determinant of newborn health. African American women are at increased risk for early birth, particularly via the inflammatory pathway. Variants of the IL1RN gene, which encode the interleukin-1 receptor antagonist (IL-1Ra) protein, are implicated in early birth. The biological pathways linking these variables remain unclear. Evidence also suggests that inflammatory pathways differ by race; however, studies among African American women are lacking. Objectives: We assessed whether an IL1RN variant was associated with timing of birth among African American women and whether this relationship was mediated by lower anti-inflammatory IL-1Ra production or related to a decrease in inhibition of proinflammatory IL-1β production. Methods: A candidate gene study using a prospective cohort design was used. We collected blood samples at 28–32 weeks of gestation among African American women experiencing an uncomplicated pregnancy (N = 89). IL1RN single-nucleotide polymorphism (SNP) rs2637988 was genotyped, and lipopolysaccharide-stimulated IL-1Ra and IL-1β production was quantified. Medical record review determined timing of birth. Results: Women with GG genotype gave birth earlier than women with AA/AG genotypes (b* = .21, p = .04). There was no indirect effect of IL1RN SNP rs2637988 allele status on timing of birth through IL-1Ra production, as evidenced by a nonsignificant product of coefficients in mediational analyses (ab = .006, 95% CI [−0.05, 0.13]). Women with GG genotype showed less inhibition of IL-1β production for a unit positive difference in IL-1Ra production than women with AA/AG genotypes (b* = .93, p = .03). Greater IL-1β production at 28–32 weeks of pregnancy was marginally associated with earlier birth (b* = .21, p = .05). Discussion: Women with GG genotype may be at risk for earlier birth because of diminished IL-1β inhibition, allowing for initiation of a robust inflammatory response upon even mild immune challenge. Study of inflammatory contributions to early birth among African American women may be key to identifying potential prognostic markers of risk and targeted preventive interventions

Does the measure of economic disadvantage matter? Exploring the effect of individual and relative deprivation on intrauterine growth restriction

This paper examines the relation between health, individual income, and relative deprivation. Three alternative measures of relative deprivation are described, Yitzhaik relative deprivation, Deaton relative deprivation, and log income difference relative deprivation, with attention to problems in measuring permanent disadvantage when the underlying income distribution is changing over time. We used data from the National Longitudinal Surveys of Youth, a US-based longitudinal survey, to examine the associations between disadvantage, measured cross-sectionally and aggregated over the life course, and intrauterine growth restriction (IUGR). We reject the hypotheses that any of the economic measures, whether permanent/contemporaneous or individual/relative, have different associations with IUGR in terms of sign and significance. There was some evidence that permanent economic disadvantage was associated with greater risk of IUGR than those on the corresponding contemporaneous measures. The fitted values from logistic regressions on each measure of disadvantage were compared with the two-way plots of the observed IUGR-income pattern. Deaton relative deprivation and log income difference tracked the observed probability of IUGR as a function of income more closely than the other two measures of relative deprivation. Finally, we examined the determinants of each measure of disadvantage. Observed characteristics in childhood and adulthood explained more of the variance in log income difference and Deaton relative deprivation than in the other two measures of disadvantage. They also explained more of the variance in permanent disadvantage than in the contemporaneous counterpart.Relative deprivation Individual income Intrauterine growth restriction (IUGR) USA