Pregnancy and vascular liver diseases Payancé, Audrey; Ceccaldi, Pierre François; De Raucourt, Emmanuelle ...
Clinics and Research in Hepatology and Gastroenterology,
September 2020, 2020-09-00, Letnik:
44, Številka:
4
Journal Article
Background. Antiretroviral (ARV) regimens during pregnancy are highly effective in preventing mother-to-child transmission of human immunodeficiency virus (HIV). Congenital heart defects (CHDs) and ...anomalies in cardiac function have been reported in zidovudine (ZDV)–exposed uninfected children. We explored these associations in a large observational cohort and a randomized clinical trial. Methods. Since 1986, the French Perinatal Cohort prospectively enrolled all HIV-infected women in 90 centers and collected follow-up on their children through 2 years of age. All CHDs were reviewed by a specialist blinded to exposures. Additionally, in a randomized trial (PRIMEVA ANRS 135) of 2 ARV regimens during pregnancy, 1 of which was without nucleoside reverse transcriptase inhibitors, infants had a specific follow-up including echocardiography at 1 month and 12 months. Results. Among 12 888 children included, ZDV exposure in the first trimester was significantly associated with CHD (1.5% vs 0.7%; adjusted odds ratio, 2.2 95% confidence interval, 1.3–3.7; P < .001). This association was significant for ventricular septal defects (1.1% vs 0.6%; P = .001) and other CHDs (0.31% vs 0.11%; P = .02). In the randomized trial, among 50 infants, girls (but not boys) exposed in utero to ZDV/lamivudine/ritonavir-boosted lopinavir (LPV/r) had a higher left ventricular shortening fraction at 1 month (40% vs 36%; P = .008), and an increased posterior wall thickness at 1 year (5.4 mm vs 4.4 mm; P = .01) than the LPV/r group. Conclusions. This study confirms a specific association between in utero exposure to ZDV and CHDs, and a longlasting postnatal myocardial remodeling in girls. A potential common mechanism, including the involvement of mitochondrial dysfunction, must be explored, and long-term consequences on cardiac function warrant specific attention. Clinical Trials Registration. NCT00424814.
Abstract
Background
Safety data about rilpivirine use during pregnancy remain scarce, and rilpivirine plasma concentrations are reduced during second/third trimesters, with a potential risk of viral ...breakthroughs. Thus, French guidelines recommend switching to rilpivirine-free combinations (RFCs) during pregnancy.
Objectives
To describe the characteristics of women initiating pregnancy while on rilpivirine and to compare the outcomes for virologically suppressed subjects continuing rilpivirine until delivery versus switching to an RFC.
Methods
In the ANRS-EPF French Perinatal cohort, we included women on rilpivirine at conception in 2010–18. Pregnancy outcomes were compared between patients continuing versus interrupting rilpivirine. In women with documented viral suppression (<50 copies/mL) before 14 weeks of gestation (WG) while on rilpivirine, we compared the probability of viral rebound (≥50 copies/mL) during pregnancy between subjects continuing rilpivirine versus those switching to RFC.
Results
Among 247 women included, 88.7% had viral suppression at the beginning of pregnancy. Overall, 184 women (74.5%) switched to an RFC (mostly PI/ritonavir-based regimens) at a median gestational age of 8.0 WG. Plasma HIV-1 RNA nearest delivery was <50 copies/mL in 95.6% of women. Among 69 women with documented viral suppression before 14 WG, the risk of viral rebound was higher when switching to RFCs than when continuing rilpivirine (20.0% versus 0.0%, P = 0.046). Delivery outcomes were similar between groups (overall birth defects, 3.8/100 live births; pregnancy losses, 2.0%; preterm deliveries, 10.6%). No HIV transmission occurred.
Conclusions
In virologically suppressed women initiating pregnancy, continuing rilpivirine was associated with better virological outcome than changing regimen. We did not observe a higher risk of adverse pregnancy outcomes.
Objective The objective of the study was to determine the placental transfer of the antiretroviral fusion inhibitor, enfuvirtide (Fuzeon). Study Design Human cotyledons were perfused for 90 minutes ...in an open dual circuit with enfuvirtide, and fetal venous samples were collected every 5 minutes. Three perfusion experiments were validated using antipyrine. Results Enfuvirtide was not detected in the fetal compartment in any of the 3 experiments. The mean concentration of the drug measured in the maternal compartment was 12,400 ng/mL (range, 6500-16,200 ng/mL), which is 2.5 times the maximum concentration recommended for patients treated with enfuvirtide. Conclusion Even at maternal concentrations twice above therapeutic levels, no placental transfer of enfuvirtide was observed. The high molecular weight of the molecule (4492 kDa) and its ionized state may account for the lack of placental transfer. This result suggests that enfuvirtide could be used in HIV-infected pregnant women without causing fetal exposure.
Background. Intrapartum intravenous zidovudine (ZDV) prophylaxis is a long-standing component of prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) in ...high-resource countries. In some recent guidelines, intravenous ZDV is no longer systematically recommended for mothers receiving combination antiretroviral therapy (cART) with low viral load. We evaluated the impact of intravenous ZDV according to viral load and obstetrical conditions. Methods. All HIV-1—infected women delivering between 1 January 1997 and 31 December 2010 in the French Perinatal Cohort (ANRS-EPF) were analyzed if they received ART during pregnancy and did not breastfeed. We identified maternal and obstetrical characteristics related to lack of intravenous ZDV and compared its association with MTCT rate and other infant parameters, according to various risk factors. Results. Intravenous ZDV was used in 95.2% of the 11 538 deliveries. Older age, multiparity, and preterm and vaginal delivery were associated with lack of intravenous ZDV (n = 554). In women who delivered with viral load ≥1000 copies/mL, the overall MTCT rate was higher without than with intravenous ZDV (7.5% vs 2.9%; P = .01); however, there was no such difference when the neonate received postnatal intensification therapy. Among them, 77% of women who had viral load <400 copies/mL, there was no difference in MTCT rate (0% without intravenous ZDV vs 0.6% with intravenous ZDV; P = .17). Intravenous ZDV was not associated with increased short-term hematological toxicity or lactate level. Conclusions. Intravenous ZDV remains an effective tool to reduce transmission in cases of virological failure, even in cART-treated women. However, for the vast majority of women with low viral loads at delivery, in the absence of obstetrical risk factors, systematic intravenous ZDV appears to be unnecessary.
The aim of this paper was to describe the time‐course of the sedative effect of rectal chloral hydrate (75 mg/kg) in children undergoing CT scan or MRI. Twenty children (2.13 ± 1.43 years old) were ...administered 75 mg/kg chloral hydrate rectally (chloralhydrat‐rectiole rectal formulation, Dr Mann‐Pharma Lab, Berlin, Germany), before a CT scan or an NMR imaging. Sedation was measured at specific times using a sedation score of 1–6. Patients were continuously monitored for respiratory and heart rate, systolic and diastolic blood pressures, and oxygen saturation. About 82.35 and 94.11% of the patients had a score of sedation ≥ 3 within 15 and 30 min, respectively. The mean time to effective sedation (score ≥ 3) was of 0.30 ± 0.14 h (median time, 0.25 h). The mean duration of effective sedation (score ≥ 3) was 1.29 ± 1.05 h (median duration, 0.75 h). A total of 93.1% of the X‐ray sections were obtained without artifact and sedation was considered by radiologists to be efficient for 83.3% of the procedures. This sedation procedure appeared efficient and safe during ambulatory CT scan and NMR imaging. The long‐term effect of chloral hydrate, however, remains to be evaluated.
Although most societies of obstetrics advocate vaginal delivery of twins, there has been a steady rise in the rate of twin cesarean sections. We risk perhaps losing in a single generation our ...obstetrical learning and skills because of medicolegal and emotionally charged issues.
We have therefore designed a realistic as possible simulation model of second twin delivery and tested it on residents in obstetrics.
Between two trials, we noted a significant improvement in the time required for internal podalic version and breech extraction. We also observed a significant improvement in the confidence score between the two trials.
We have designed a simulation device that improves obstetrical skills for second twin delivery and which we hope will participate in the comeback of vaginal delivery for this indication and contribute to the fight against the dangerous trend of rising rates of cesarean delivery for twins. Our model completely fits the paradigm of simulation in medical pedagogy.
Portal vein cavernoma (PVC) is a rare disease resulting from extrahepatic portal vein thrombosis and development of collateral venous circulation. The management of pregnancy and delivery in woman ...with PVC has rarely been described.
Two primiparous women are presented to illustrate the management of PVC during pregnancy and discuss the delivery route according to the symptoms and the PVC complications. The first patient presented PVC associated with large jejunal varices and high anticardiolipid antibodies. She was treated with beta-blocker therapy and low molecular weight heparin during pregnancy, and delivered by cesarean section. The second patient presented protein S deficiency complicated by PVC and thrombocytopenia and delivered vaginally without complications.
Many issues should be considered when counseling women with PVC, including the management before and during pregnancy according to symptoms and PVC complications. A multidisciplinary approach seems to be key to the management of delivery. Our advice to caregivers is that elective cesarean section seems necessary in cases with digestive varices. Vaginal delivery, with a passive second stage, seems to be relatively safe and less morbid in women without digestive varices, when maternal and fetal tolerance permits.
The management of a pregnant woman with an acute non-obstetrical disease must be made in narrow collaboration with an obstetrician. This one must be warned from the beginning of the care of the ...patient. In a pregnant woman, any acute medical, surgical or traumatic non-obstetrical disease can have obstetrical consequences. The diagnostic and therapeutic management of an acute non-obstetrical disease can have iatrogenic consequences during pregnancy. The most often described risks are early pregnancy loss, intra-uterine fetal death, placenta abruption, direct fetal hurts, preterm labor, prematurity and its complications. Obstetrical complications can induce maternal and neonatal life-threatening risks. Simple and easily accessible examinations in emergency allow detecting the obstetrical consequences of an acute non-obstetrical disease. During the management of an acute non-obstetrical disease in a pregnant woman, the induced obstetrical consequence of the disease can require emergency action of the obstetrician in conditions associated with maternal life-threatening risk. During the management of an acute non-obstetrical disease in a pregnant woman, once the mother condition was stabilized, the obstetrician had to estimate the fetal consequences and to adapt his or her therapeutic attitude. He or she sets up the fetal and placental surveillance adapted to the obstetrical risks and decides on the duration of this surveillance.
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