Chronic carriers of HBV had a minimally increased risk of preterm birth and low birth weight but the risk was more pronounced in women with positive HBeAg status. Women with positive HBeAg status also had an increased risk of GDM.
Background
The impact of pregnancy on efavirenz pharmacokinetics is unknown.
Methods
International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1026s is an on-going, prospective, non-blinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving 600 mg efavirenz once daily as part of combination antiretroviral therapy. Intensive steady-state 24-hour blood sampling was performed during the third trimester and at 6–12 weeks postpartum. Maternal and umbilical cord blood samples were drawn at delivery. Pharmacokinetics targets were the estimated 10th percentile efavirenz AUC in non-pregnant historical controls (40.0 mcg.hr/mL) and a trough concentration of 1 mcg/mL.
Results
Twenty five women were enrolled during the third trimester: median (range) age was 29.3 (18.9–42.9) years, weight 69.0 (40–130) kg, gestational age 32.9 (30.1–38.7) weeks. Median (range) efavirenz AUC0-24, Cmax and C24hour were 55.4 mcg.hr/mL (13.5–220.3), 5.4 mcg/mL (1.9–12.2) and 1.6 mcg/ml (0.23–8.13), respectively. Efavirenz AUC and Cmax did not differ during pregnancy and postpartum but C24hour was lower during the third trimester (1.6 vs. 2.1 mcg/mL, p=0.01). During the third trimester, 5 of 25 (20%) women had an efavirenz AUC below the target and 3 of 25 (12%) had a trough concentration below 1 mcg/mL. Efavirenz cord blood/maternal concentration ratio was 0.49 (0.37–0.74). All women had a HIV-1 RNA viral load less than 400 copies/mL at delivery and 19 (76%) had a viral load below 50 copies/mL. One child was perinatally HIV-infected. Three women were exposed to efavirenz throughout the first 6 weeks of pregnancy. EFV was well tolerated and among the 25 infants no congenital anomalies or newborn complications were reported.
Conclusions
Changes in efavirenz pharmacokinetics during pregnancy compared to postpartum are not sufficiently large enough to warrant a dose adjustment during pregnancy.
Prenatal diagnosis of severe thalassaemia is conventionally diagnosed by fetal DNA analysis but it can not be widely used due to its drawbacks of high cost and technical effort. This prospective study describes a new prenatal strategy in preventing severe thalassaemia by a more simple and inexpensive way. The strategy included: (1) genetic counselling; (2) identification of pregnancies at risk by retrospective screening (history of known risk) and prospective screening for asymptomatic women; (3) cordocentesis at 16-22 weeks' gestation; (4) fetal blood analysis with high performance liquid chromatography (HPLC); (5) termination of affected pregnancy. The prospective screening consisted of 2 min osmotic fragility (OF) and HbE screening test in women with no risk, and testing the husbands of the women with a positive result. If both of the couple had a positive result, the diagnostic test (HbA(2) level and PCR alpha-thal 1) for the carrier was needed. A pregnancy in which both of the couple were carriers was considered at risk. This strategy identified 181 and 108 couples at risk by prospective (from 7954 pregnancies) and retrospective screening, respectively. Two hundred and forty-two underwent cordocentesis, 108 from retrospective screening and 134 from prospective screening, and 62 were proven to have severe thalassaemia (29 and 33 in retrospective and prospective screening, respectively). The strategy identified nearly all, if not all, fetuses with severe thalassaemia without false positives among the screened couples. In conclusion, the strategy proves to be highly effective in the control of severe thalassaemia.
The strategy proves valuable in the control of severe thalassemia. This extensive experience suggests the strategy be considered an effective way in the control of severe thalassemia in high prevalence areas.
The frequency and the cellular basis for HIV-1 transmission from mother to child in the early gestational period are poorly understood. We compared the placentas of 24 women seropositive for HIV-1 subtype E and who had not received any antiretroviral drugs, to placentas of 25 seronegative women. All placentas were obtained during therapeutic abortion at 6-23 weeks gestation. Placentas and fetal organs were examined by routine light microscopy, immunostaining for p24 capsid protein, and in situ PCR to localize which cells were infected with HIV-1 subtype E. The number of previous abortions was not a factor in placental HIV infection since this number was higher in seronegative women (Po0.01). There were no significant differences between the placentas of the two groups with respect to presence of chorioamnionitis, villitis, villous stromal fibrosis, infarction, abnormal villous maturation, deciduitis or decidual necrosis. HIV-1 subtype E was detected in up to 83% of placentas, either by immunostaining or in situ PCR, in trophoblast, villous stromal cells, Hofbauer cells, decidual and decidual glandular epithelium. Fetal organs were positive for HIV in 30% (6/20) of cases. There was a significant association between transmission of HIV to the fetus and the histologic findings of chorioamnionitis, plasmacellular deciduitis and decidual cell necrosis. This is the first report showing an association of chorioamnionitis with early in utero transmission of HIV-1 subtype E. This may help explain the cases of in utero transmission that persist despite antiretroviral prophylaxis, given that therapy is started in the late gestational period.
The model could prenatally identify affected fetuses with a detection rate and negative predictive value of 100%. The model was highly effective to prenatally detect affected fetuses with an acceptable false positive rate.
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