Cross-Generational Contributors to Preterm Birth in California: Singletons Based on Race/Ethnicity.

OBJECTIVE: Multiple studies have examined cross-generational patterns of preterm birth (PTB), yet results have been inconsistent and generally focused on primarily white populations. We examine the cross-generational PTB risk across racial/ethnic groups. STUDY DESIGN: Retrospective study of 388,474 grandmother-mother-infant triads with infants drawn from birth registry of singleton live births between 2005 and 2011 in California. Using logistic regression (odds ratios [ORs] and confidence intervals [CIs]), we examined the risk of preterm delivery by gestational age, sociodemographic, socioeconomic, and obstetric clinical characteristics stratified by maternal race/ethnicity. RESULTS: The risk of having a preterm infant <32 weeks was greater for women born at <32 weeks (OR: 2.09, 95% CI: 1.62-2.70) and 32 to 36 weeks (OR: 1.51, 95% CI: 1.35-1.70). This increased risk of preterm delivery was present among women in all race/ethnicity groups (white [AOR: 2.00, 95% CI: 1.52-2.63), black [AOR: 1.79, 95% CI: 1.37-2.34], Hispanic [AOR: 2.39, 95% CI: 2.05-2.79], and Asian [AOR: 2.12, 95% CI: 1.20-3.91]), with hypertension as the only consistent risk factor associated with increased risk of preterm delivery. CONCLUSION: Our findings suggest a cross-generational risk of PTB that is consistent across race/ethnicity with hypertension as the only consistent risk factor.

Down-regulation of the placental BCRP/ABCG2 transporter in response to hypoxia signaling.

INTRODUCTION: The BCRP/ABCG2 efflux transporter protects the developing fetus by limiting the transplacental transfer of drugs and chemicals and prevents the apoptosis of trophoblasts. The purpose of this study was to determine whether hypoxia-related signaling alters placental BCRP expression and function in vitro and in human pregnancies. METHODS: Human BeWo choriocarcinoma cells were treated with the hypoxia mimetic, cobalt chloride (CoCl2), or 3% oxygen for 24-48 h. Activation of HIF-1α signaling and regulation of BCRP was assessed using qPCR, ELISA, western blotting and a fluorescent substrate transport assay. In addition, healthy term placentas from high altitude pregnancies with chronic hypoxia were assessed for BCRP expression. RESULTS: CoCl2 and 3% oxygen increased HIF-1α protein signaling and decreased the mRNA and protein expression of BCRP by 30-75% in BeWo cells. Reduced BCRP expression corresponded with impaired efflux activity during hypoxia as evidenced by accumulation of the substrate Hoechst 33342. A number of transcription factors known to regulate BCRP, including AHR, NRF2 and PPARγ, were also coordinately down-regulated by 3% oxygen in BeWo cells. Moreover, women who gave birth at a high altitude (3100 m) exhibited signs of chronic placental hypoxia, including enhanced protein expression of the HIF-1α target GLUT1, and had reduced BCRP levels in microvillous membranes compared to women at a moderate altitude (1600 m). DISCUSSION: This study provides novel insight into the regulation of the placental BCRP transporter by hypoxia, which may be important for exposure of the fetus to chemicals during early development and in hypoxia-related pregnancy disorders.