Grazielle Rodrigues

and 9 more

Aims: No study has evaluated the BET pharmacokinetics in twin pregnancies separated by chorionicity. The aim this study is to describe and compare the BET pharmacokinetic parameters in singleton, dichorionic (DC) and monochorionic (MC) twin pregnancies in the third trimester of pregnancy. Methods: Twenty-six pregnant women received an intramuscular dose of 6 mg of BET sodium phosphate plus 6 mg BET acetate. Serial blood samples were collected for 24 hours after the first intramuscular BET esters dose. BET plasma concentrations were quantified using a validated HPLC analytical method. BET pharmacokinetic parameters were obtained employing a non-compartment model, and were compared using ANOVA’s test with Tukey’s multiple comparisons test. Correlations between clinical features and pharmacokinetic parameters were analyzed using Pearson’s correlation. Preliminary data on the BET placental transfer were also presented. Results: The geometric mean (IC 95%) of AUC0-∞ 670.0 (504.3-805.2) vs 434.9 (311.2-539.6) ng.h/mL and the CL/F 18.38 (13.84-22.65) vs 29.40 (21.17-36.69) were significantly lower and higher, respectively, in DC twin pregnancies compared to singleton. Others pharmacokinetic parameters did not differ among the groups. Conclusions: Data from this study suggest that the presence of two fetoplacental units may increase the BET metabolism by CYP3A4 enzyme and increase its elimination. Pharmacokinetic-pharmacodynamic clinical studies are needed to investigate whether this BET pharmacokinetic changes have clinical repercussions for the newborns and require dose adjustment in DC twin pregnancies.

Conrado Coutinho

and 15 more

Objective: To define the prevalence of adverse outcomes according to the gestational age of maternal infection in a large cohort of ZIKV-infected Brazilian women and their infants. Design: Prospective, population-based cohort study. Setting: Ribeirão Preto’s region private and public health facilities. Population: All pregnant women with confirmed ZIKV-infection and their infants. Methods: Prenatal/early neonatal data were obtained for all pairs. A subgroup of infants had cranial ultrasonography, eye fundoscopy, hearing, neurological exam, and Bayley III screening test within 3 months of age. Main Outcome Measures: Prevalence of pregnancy losses, anomalies detected at birth or within 3 months according to the gestational age of infection. Results: 511 women with ZIKV were identified from a total of 1116 women with flavivirus-type symptoms. Pregnancy losses 24/511(4.7%) and/or ZIKV-related anomalies occurred in 43/511(8.4%) mothers. Microcephaly or other CNS malformations were diagnosed in 1/4(25.0%) of the stillbirths and 19/489[3.9%;CI95%:2.5-5.9] of the live-born infants, with 13/513[2.5%;CI95%:1.5-4.3] neonates presenting major signs of CZS. Fetal abnormalities were 14.0(CI95%:7.6-26.0) times more likely with gestational infection <11 weeks. Among 280 asymptomatic evaluated infants, 2/155(1.3%) had eye abnormalities, 1/207(0.5%) CNS imaging significant findings, and 16/199(8%) neurological alert signs. Conclusions: This prospective, population-based study represents the largest Brazilian cohort of ZIKV in pregnancy. Congenital anomalies potentially associated with CZS are less frequent than previously thought. There is a strong relationship between the gestational age of infection (<11 weeks) and worse early infant prognosis. A notable proportion of apparently asymptomatic newborns can present with subclinical findings within 3 months of age. Funding: FAEPA/SES-SP