An infection with the Zika virus (ZIKV) is usually mild, with nonspecific symptoms and most often asymptomatic. However, because of its causal relationship with severe congenital malformations, the ZIKV epidemic became an imperative for mobilization, renewed strategies for vector control, and biomedical research. A congenital Zika syndrome (CZS) has been characterized with 5 distinctive features that focus on brain development abnormalities (including microcephaly and brain calcifications), retinal manifestations, and defects on extremities including congenital contractures and hypertonia. The CZS could be just “the tip of the iceberg”, pending the documentation of a spectrum of disease that could manifest later in life, from mild dysfunction to severe disease. It will be a matter of time for neurodevelopmental abnormalities, learning disabilities, and other unknown but yet-to-be-described outcomes to be associated with intrauterine ZIKV infection. In addition, ZIKV infection during pregnancy has been associated with other adverse outcomes. Reports mostly include ZIKV-affected pregnancies, and it will be difficult to clearly establish causality without appropriate control groups. We are summarizing some of the known or reported consequences of such infection during pregnancy. Women of reproductive age and particularly pregnant women are the most vulnerable to the adverse consequences of the ZIKV epidemic. Vector control programs need to be expanded to curtail new infections. Research is needed to develop safe and effective treatments, a preventive or therapeutic vaccine, and specific and sensitive tests and to diagnose and identify correlates of long-term immunity. Vaccines and treatments should be safe to be used in pregnancy. To do nothing would allow thousands of pregnant women to expose their fetuses to an infection that causes birth defects and other problems. Prenatal diagnosis technology development is necessary to be able to predict or diagnose adverse fetal outcomes related to ZIKV. Moreover, these tests should be used in a manner similar to the testing/screening method for neural tube defects and common chromosomal anomalies during prenatal care.

Until recently, Zika virus (ZIKV) infections were considered mild and self-limiting. Since 2015, they have been associated with an increase in microcephaly and other birth defects in newborns. While this association has been observed in case reports and epidemiological studies, the nature and extent of the relationship between ZIKV and adverse pregnancy and pediatric health outcomes is not well understood. With the unique opportunity to prospectively explore the full spectrum of issues related to ZIKV exposure during pregnancy, we undertook a multi-country, prospective cohort study to evaluate the association between ZIKV and pregnancy, neonatal, and infant outcomes. At research sites in ZIKV endemic regions of Brazil (4 sites), Colombia, Guatemala, Nicaragua, Puerto Rico (2 sites), and Peru, up to 10,000 pregnant women will be recruited and consented in the first and early second trimesters of pregnancy and then followed through delivery up to 6 weeks post-partum; their infants will be followed until at least 1 year of age. Pregnant women with symptomatic ZIKV infection confirmed by presence of ZIKV RNA and/or IgM for ZIKV will also be enrolled, regardless of gestational age. Participants will be tested monthly for ZIKV infection; additional demographic, physical, laboratory and environmental data will be collected to assess the potential interaction of these variables with ZIKV infection. Delivery outcomes and detailed infant assessments, including physical and neurological outcomes, will be obtained. With the emergence of ZIKV in the Americas and its association with adverse pregnancy outcomes in this region, a much better understanding of the spectrum of clinical outcomes associated with exposure to ZIKV during pregnancy is needed. This cohort study will provide information about maternal, fetal, and infant outcomes related to ZIKV infection, including congenital ZIKV syndrome, and manifestations that are not detectable at birth but may appear during the first year of life. In addition, the flexibility of the study design has provided an opportunity to modify study parameters in real time to provide rigorous research data to answer the most critical questions about the impact of congenital ZIKV exposure. NCT02856984. Registered August 5, 2016. Retrospectively registered.

During a disaster, pregnant women are considered among the most vulnerable. Background: On 20 September 2017, the Caribbean was hit by a category 4 hurricane. The purpose of the study was to explore the impact on pregnant women during and after the hurricane regarding access to health care, social services, and support systems. Methods: In-depth interviews were conducted to 10 women that were pregnant during the event. Qualitative inquiry based on the Interpretative Phenomenological Analysis framework was used to interpret the narratives. Results: Five major themes emerged: meaning of living through a disaster, fear, the dual burden of protecting themselves and their unborn baby, disruption in health care, and coping mechanisms. Despite the negative feelings, most participants experienced positive transformations. They narrated how they stayed calm and coped in order to protect their pregnancy. Their overall evaluation of the healthcare system was positive. The support of friends and family was crucial pre and post-disaster. Conclusions: The interviews provided a wealth of firsthand information of women experiencing a natural disaster while pregnant. The findings underscore the need to incorporate emotional support in the preparedness and response plans for pregnant women. Educating, empowering, and incorporating families and communities is vital in these efforts.

Treatment of HIV-1-infected women during pregnancy protects maternal health and reduces the risk of perinatal transmission of HIV-1. However, physiologic changes that occur during pregnancy may affect drug pharmacokinetics. This phase IIIb, open-label study evaluated the effects of pregnancy on the pharmacokinetics of the nonnucleoside reverse transcriptase inhibitor etravirine. Eligible HIV-1-infected pregnant women (18-26 weeks gestation) on an individualized, highly active antiretroviral therapy regimen including etravirine 200 mg twice daily were enrolled. Blood samples to assess the pharmacokinetics of total and unbound etravirine were obtained at clinic visits during the second and third trimesters (24- to 28-weeks and 34- to 38-weeks gestation, respectively) and 6-12 weeks postpartum. At each time point, plasma concentrations were measured over 12 hours (12-hour time point was obtained before the second daily dose of etravirine); pharmacokinetic parameters were derived using noncompartmental analysis and were compared between pregnancy and postpartum using general linear models. Antiviral and immunologic response and safety were assessed at each visit. Etravirine pharmacokinetic profiles were available for 13 of 15 enrolled women. Exposure to total etravirine was generally higher during pregnancy compared with 6-12 weeks postpartum (1.2- to 1.4-fold); the differences were less pronounced for unbound (pharmacodynamically active) etravirine. Virologic response was generally preserved throughout the study, and no perinatal transmission was observed. Etravirine was generally safe and well tolerated. Etravirine 200 mg twice daily, as part of individualized combination antiretroviral therapy, may be a treatment option for HIV-1-infected pregnant women.

Since 1982 we have accelerated fetal maturation with intra‐amniotic thyr‐oxine (T4) in more than 140 patients. The purpose of this analysis was to determine the rate of change of the ratio of lecithin to sphingomyelin (LIS) after administration of T4 at different gestational ages, and to compare the responses to the first and the second administration of T4. Fifty‐nine cases in which administration of T4 was continued for 2 weeks or more, and in which at least 3 determinations of L/S had been performed, were identified. Gestational age of the fetus at the inititiation of treatment ranged from 26 to 31 weeks (mean 29.3 weeks). Thyroxine was administered weekly in 200 to 500 mcg doses.Administration of T4 prior to the 27th week did not change the L/S. From the 27th and 31st week of gestation, the slope of the L/S, after the initial dose of T4 increased from 0.331wk to 1.05/wk. In contrast the slope of the untreated patients changed little reaching a maximum of 0.22 at the 33 week. L/S>2 was observed in 80% of cases after 2 weeks of therapy, when it had been initiated after the 26th week.The response to the second dose was about twice that of the first in fetuses 5 30 weeks, but was similar to that seen after the initial dose in fetuses >30 weeks. Phosphatidylglycerol (PG) was detected in amniotic fluid in 51% of cases after 2 weeks of treatment, and in 6 instances as early as at the 30th week.Responsiveness of L/S to T4 treatment of the fetus is a function of gestational age and of prior exposure to T4.

Objective: In AIDS Clinical Trials Group study A5316, efavirenz lowered plasma concentrations of etonogestrel and ethinyl estradiol, given as a vaginal ring, while atazanavir/ritonavir increased etonogestrel and lowered ethinyl estradiol concentrations. We characterized the pharmacogenetics of these interactions. Methods: In A5316, women with HIV enrolled into control (no antiretrovirals), efavirenz [600 mg daily with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)], and atazanavir/ritonavir (300/100 mg daily with NRTIs) groups. On day 0, a vaginal ring was inserted, releasing etonogestrel/ethinyl estradiol 120/15 μg/day. Intensive plasma sampling for antiretrovirals was obtained on days 0 and 21, and single samples for etonogestrel and ethinyl estradiol on days 7, 14, and 21. Seventeen genetic polymorphisms were analyzed. Results: The 72 participants in this analysis included 25, 24 and 23 in the control, efavirenz, and atazanavir/ritonavir groups, respectively. At day 21 in the efavirenz group, CYP2B6 genotype was associated with increased plasma efavirenz exposure ( P = 3.2 × 10 ⁻³ ), decreased plasma concentrations of etonogestrel ( P = 1.7 × 10 ⁻³ ), and decreased ethinyl estradiol ( P = 6.7 × 10 ⁻⁴ ). Compared to controls, efavirenz reduced median etonogestrel concentrations by at least 93% in CYP2B6 slow metabolizers versus approximately 75% in normal and intermediate metabolizers. Efavirenz reduced median ethinyl estradiol concentrations by 75% in CYP2B6 slow metabolizers versus approximately 41% in normal and intermediate metabolizers. Conclusion: CYP2B6 slow metabolizer genotype worsens the pharmacokinetic interaction of efavirenz with hormonal contraceptives administered by vaginal ring. Efavirenz dose reduction in CYP2B6 slow metabolizers may reduce, but will likely not eliminate, this interaction.