Mid-pregnancy circulating cytokine levels, placental efficiency and their relationship with preterm birth.

Objective: To assess a panel of cytokines and placental insufficiency with the risk of preterm delivery (PTD). Methods: Nested case-control study into the BRISA birth cohort. Eighty-two mother-infant-placenta pairs were selected at 20+0 to 25+6 weeks. Circulating biomarker levels were performed using Luminex flowmetric xMAP technology. Cytokines classified as Th1, Th2 or Th17 and other biomarkers were selected. The ratio between birth weight and placental weight (BW/PW) was used as a proxy for placental efficiency. Spearman correlation, univariate analyses and logistic regression models were calculated. Sensitivity, specificity, positive and negative likelihood ratios were calculated using the Receiver Operating Characteristic curve. Results: Mean gestational age was 250 days, 14,6% were small for gestational age, 4,8% large for gestational age and 13,4% stunted. Placental efficiency was higher for term newborns (p<0,001), and 18/22 (81%) preterm biomarker values were higher than the control group. Th1 cytokines were highly correlated, while the weakest correlation was observed in other biomarkers. Less education was associated with a higher risk of PTD (p = 0.046), while there was no appreciable difference in the risk of PTD for placental insufficiency. Biomarkers showed negligible adjusted OR of PTD (0.90 to 1.02). IL-6, IL-8, IL-1ß, TNFß, IL-4, IL-13, GCSF, MIP1A, VEGF, EGF, and FGF2 presented a higher sensitivity ranging from 75.56% to 91.11%. Conclusion: IL-8, IL-12p40, IL-4, IL-13, GCSF, MIP1B, and GMSF in asymptomatic pregnant women were associated with PTD. This finding suggests an activation of maternal inflammatory response.

Preterm birth and postpartum depression within 6 months after childbirth in a Brazilian cohort.

Preterm birth (PTB) and postpartum depression (PPD) are important public health issues, and although literature mainly supports the association between them, some reviews have highlighted methodological limitations in the studies in this field, restricting the interpretation of such finding. This study aimed at assessing the association between PTB and PPD, by comparing groups of preterm and full-term mothers in two Brazilian cities with contrasting sociodemographic indicators. This prospective convenience cohort study assessed 1421 women during pregnancy, at childbirth, and in the postpartum period. The Edinburgh Postnatal Depression Scale (EPDS) was administrated to assess PPD within 6 months after delivery and women were considered probably depressed if scores were EDPS ≥ 12. PTB was defined as the delivery before 37 completed weeks of pregnancy. A multivariate Poisson regression was used to estimate relative risk for PPD in mothers of preterm infants, and the final analysis models were adjusted for psychosocial variables, selected according to the directed acyclic graph (DAG) approach. Frequencies of PPD were not significantly different in mothers of preterm and full-term infants, in neither city. In the final adjusted model, PTB was not associated with PPD. The association between PTB and PPD was not confirmed in two large samples from two Brazilian cities with contrasting socioeconomic profile. However, maternal health during pregnancy plays an important role in predicting PPD. Prenatal care should promote maternal mental health as an effort towards decreasing unfavored outcomes for mothers, infants, and families.

Enhanced elimination of betamethasone in dichorionic twin pregnancies.

AIM: No study has evaluated the betamethasone pharmacokinetics in twin pregnancies according to chorionicity. This study aimed to describe and compare the betamethasone pharmacokinetic parameters in singleton and dichorionic (DC) and monochorionic twin pregnancies in the third trimester of pregnancy. METHODS: Twenty-six pregnant women received 2 intramuscular doses of 6 mg of betamethasone sodium phosphate plus 6 mg betamethasone acetate due to preterm labour. Serial blood samples were collected for 24 hours after the first intramuscular dose of betamethasone esters. Betamethasone plasma concentrations were quantified using a validated liquid chromatography-tandem mass spectrometry analytical method, and the pharmacokinetic parameters were obtained employing a noncompartmental model. Preliminary data on the betamethasone placental transfer are also presented. RESULTS: The geometric mean (95% confidence interval) of AUC0-∞ 645.1 (504.3-825.2) vs. 409.8 (311.2-539.6) ng.h/mL and CL/F 17.70 (13.84-22.65) vs. 27.87 (21.17-36.69) were significantly different, respectively, in singleton pregnancies when compared to DC twins. CONCLUSION: Data from this study suggest that the presence of 2 foetoplacental units may increase the betamethasone metabolism by hepatic CYP3A4 and/or placental 11ß-HSD2 enzymes. Pharmacokinetic-pharmacodynamic clinical studies are needed to investigate whether these betamethasone pharmacokinetic changes have clinical repercussions for the newborns and require dose adjustment in DC twin pregnancies.