Emmanuelle Pannier

Fertility after conservative treatment of placenta accreta

OBJECTIVE To report a pregnancy with vaginal delivery after a preceding pregnancy complicated by placenta accreta that was managed conservatively. DESIGN Case report. SETTING University medical center. PATIENT(S) A patient with placenta accreta that was managed conservatively. INTERVENTION(S) The placenta was left in situ and both uterine arteries were embolized. MAIN OUTCOME MEASURE(S) Preservation of reproductive capacity. RESULT(S) The patient had a term pregnancy with uncomplicated vaginal delivery. CONCLUSION(S) Pregnancy is possible after conservative treatment of placenta accreta. This treatment should be considered in the appropriate circumstances to preserve reproductive capacity.

Amniocentesis and mother-to-child human immunodeficiency virus transmission in the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales French Perinatal Cohort.

OBJECTIVE The objective of the study was to investigate whether performing an amniocentesis increased mother-to-child transmission of human immunodeficiency virus (HIV)-1 (MTCT). STUDY DESIGN We studied HIV -1 infected mothers and their children enrolled in the multicenter French Perinatal HIV Cohort from 1985 to 2006. RESULTS One hundred sixty-six amniocenteses were performed among 9302 singleton pregnancies, the proportion increasing from 1.0% before 2001 to 4.7% in 2005-2006. Use of highly active antiretroviral therapy (HAART) was more frequent in the amniocentesis group (58.4% vs 33.2%). MTCT tended to be higher in the amniocentesis group, among mothers who received no antiretroviral agents (25.0%; 3/12 vs 16.2%; 343/2113; P = .41) as well as among mothers receiving zidovudine monotherapy or a double-nucleoside reverse transcriptase inhibitor combination (6.1%; 3/49 vs 3.3%; 117/3556; P = .22), but the difference was not significant. Among 81 mothers receiving HAART, there was no case of MTCT. CONCLUSION Our results suggest that amniocentesis is not a major risk factor for mother-to-child transmission in mothers treated with effective antiretroviral therapy.

Pregnancies in systemic necrotizing vasculitides: report on 12 women and their 20 pregnancies

OBJECTIVES To describe pregnancies of women with systemic necrotizing vasculitides (SNVs), i.e. PAN, WG, Churg-Strauss syndrome (CSS) or microscopic polyangiitis (MPA), followed over the past 15 years at four French centres. METHODS Retrospective analysis of women whose SNV appeared during pregnancy or who became pregnant after SNV diagnosis. RESULTS Among the 12 women identified, one experienced rupture of pancreatic artery microaneurysms at 27 weeks revealing PAN, leading to surgical haemostasis and caesarean delivery. Eleven others started 19 pregnancies after SNV diagnosis (8 in four WG, 6 in three CSS, 1 each in three PAN and 2 in one MPA); 14 conceived during vasculitis remission. Two ended in first-trimester abortions, four miscarried; the remaining 13 pregnancies yielded 14 live newborns (1 twin pregnancy), with 7 pre-term births. Life-threatening complications occurred during 3 of these latter 13 pregnancies and required caesarean delivery. The twin pregnancy (in a CSS patient with initial vasculitis-related cardiac involvement, but in remission at conception) was complicated by transient maternal cardiac failure at 32 weeks. One WG patient with vasculitis-related renal damage developed thrombotic microangiopathy-associated renal impairment at 32 weeks, and another WG patient had severe pneumonia at 37 weeks. Other pregnancies were uneventful or with minor vasculitis manifestations. CONCLUSION Pregnant SNV patients should be monitored closely, because miscarriages and pre-term births are not uncommon. Pregnancy does not seem to have a major impact on vasculitis activity. However, life-threatening manifestations can occur, especially in patients with vasculitis-related cardiac or renal damage.

Pregnancy-Related Effects on Tenofovir Pharmacokinetics: a Population Study with 186 Women

ABSTRACT According to the European AIDS Clinical Society, tenofovir disoproxil fumarate can be used in HIV-infected pregnant women if started prior to pregnancy, although no data are available on the pharmacokinetics of tenofovir (TFV) during pregnancy. The aim of this study was to describe TFV pharmacokinetics in HIV-infected women and to evaluate the effect of pregnancy on TFV disposition. Samples were collected according to a therapeutic drug monitoring in 186 women, including 46 pregnant women treated with TFV and retrospectively analyzed by a population approach. TFV pharmacokinetics were ascribed to an open two-compartment model with linear absorption and elimination. The mean population parameter estimates (between-subject variability) were as follows: absorption rate constant, 0.56 h−1; elimination clearance, 59.9 liters h−1 (0.436); central volume of distribution, 552 liters (1.96); intercompartmental clearance, 172 liters/h; and peripheral volume of distribution, 1,390 liters. Pregnant women had a 39% higher apparent clearance compared to nonpregnant women. Apparent clearance significantly decreased with age. In order to obtain an exposure similar to the known exposure in adults and guarantee similar trough concentrations (Cmin) as observed in adults, an increase in the TFV dose should be considered for women from the second trimester to delivery.

Is Intrapartum Intravenous Zidovudine for Prevention of Mother-to-Child HIV-1 Transmission Still Useful in the Combination Antiretroviral Therapy Era?

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.

Dating biometry during the first trimester: accuracy of an every-day practice

OBJECTIVE The goal of this study was to determine the accuracy of an every-day practice for assessing gestational age by ultrasound measurement of the greatest embryonic length (GEL). DESIGN This retrospective study used measurements taken during the first trimester. SUBJECTS We considered all births in this hospital between 1 January 1992 and 31 December 1994 from pregnancies that began by an in-vitro fertilization procedure (IVF). We examined 143 consecutive files, containing 257 measurements made by 72 different operators. METHODS The precision of seven embryo growth curves was compared. We calculated for each curve its ability to predict (95% prediction interval) the date the pregnancy began, using these dated pregnancies. RESULT For GEL measurements between 3 and 80 mm, which includes most of our population, Robinson and Wisser (2) were the most appropriate curves. The 95% prediction interval was 9.5 and 10.2 days respectively. CONCLUSION Dating pregnancies in every-day practice with GEL is nearly as accurate as prospective studies with only one or two scanners.

Twin pregnancy as a risk factor for mother-to-child transmission of HIV-1: trends over 20 years.

ObjectiveWe investigated whether twin pregnancies were at increased risk of mother-to-child HIV-1 transmission (MTCT), in comparison with singletons. MethodsAmong HIV-1 infected women enrolled in the French Perinatal HIV Cohort (n = 9262), we studied the association between twin deliveries and MTCT rate according to three time periods (pre-1994, 1994–1996, 1997–2004) and the effect of birth order. The mother was considered to have transmitted if at least one of the twins was infected. Univariate and multivariate analyses of risk factors for MTCT were performed for deliveries in the periods up to 1996. ResultsOverall, 2.1% (192/9262) of all the deliveries were twins. The rate of prematurity was greater in twins than in singletons (54% and 13%, respectively). Up to 1996 the rate of MTCT of HIV-1 was 28.3% (15/53) in twin pregnancies, versus 13.5% (414/3077) in singletons [odds ratio (OR), 2.5; 95% confidence interval (CI), 1.4–4.7; P = 0.002; adjusted OR, 2.3: 95% CI, 1.1–2.3; P = 0.03). In the period from 1997 to 2003, MTCT was low and did not differ between twins (1.0%) and singletons (1.8%; P = 1.0). Overall, the transmission rate for the first-born child was threefold that for the second-born child (14/164, 8.5% versus 4/164, 2.4%; P = 0.008). ConclusionTwin pregnancies were at increased risk of transmission, but in the era of HAART this risk was reduced for twins, as well as singletons. Management of multiple pregnancies should take into account the risks of premature rupture of the membranes and preterm delivery.

Population analysis of the pregnancy-related modifications in lopinavir pharmacokinetics and their possible consequences for dose adjustment

OBJECTIVES To investigate the possible necessity of an increase in lopinavir dose during pregnancy in order to achieve the concentrations previously defined as predictive of virological efficacy. PATIENTS AND METHODS Lopinavir pharmacokinetics were investigated by a population approach performed on 145 HIV-infected women, including 74 pregnant women. The final model was used to determine the probability of achievement of the target trough concentrations by Monte Carlo simulations. RESULTS The typical population estimates (inter-individual variability %) of apparent clearance (CL/F) and volume of distribution were 4.38 L/h (24%) and 58.4 L (59%), respectively. Pregnancy associated with a gestational age >15 weeks and delivery were found to increase lopinavir CL/F by 39% and 58%, respectively. With the standard 400 mg twice-a-day regimen, the probability of reaching the 1 mg/L target trough concentration for protease inhibitor (PI)-naive patients was 99% and 96% for non-pregnant and pregnant women, respectively. An important decrease in the probability of achieving the 5.7 mg/L target trough concentration for salvage therapy was observed for non-pregnant women (55%), this decrease being even greater for pregnant women (21%). Raising the lopinavir dose to 600 mg twice daily increased these probabilities to 87% and 53% for non-pregnant and pregnant women, respectively. CONCLUSIONS Modification of the lopinavir dose is unlikely to be required for PI-naive pregnant women; however, in pregnant women who have previously received a PI, therapeutic drug monitoring and/or empirical increasing of the dose should be considered.

Pregnancy-Related Effects on Lamivudine Pharmacokinetics in a Population Study with 228 Women

ABSTRACT The aim of this study was to describe lamivudine (3TC) pharmacokinetics (PK) in HIV-infected nonpregnant and pregnant women and their fetuses. Samples were collected according to therapeutic drug monitoring from 228 women treated with lamivudine and retrospectively analyzed by a population approach. The samples were also collected from cord blood and amniotic fluid at birth. Lamivudine pharmacokinetics were ascribed to an open two-compartment model with linear absorption and elimination. Mean population parameter estimates (intersubject variability) for women were an absorption rate constant of 1.04 h−1, an elimination clearance rate of 23.6 (0.266) liters · h−1, a central volume of distribution of 109 (0.897) liters, an intercompartmental clearance rate of 6.7 liters/h, and a peripheral volume of distribution of 129 liters. A fetal compartment was linked to maternal circulation by mother-to-cord (or fetus) and cord-to-mother rate constants of 0.463 h−1 and 0.538 h−1, respectively. The amniotic fluid compartment was connected to the fetal compartment with an elimination rate constant of 0.163 h−1 and a fixed-constant swallowing flow. The placental transfer expressed as fetal-to-maternal area under the concentration-time curve (AUC) ratio was 0.86, and the lamivudine amniotic fluid accumulation, expressed as the amniotic fluid-to-fetal AUC ratio, was 2.9. Pregnant women had a 22% higher apparent clearance than nonpregnant and parturient women; however, this increase did not lead to subexposure and should not require a dosage adjustment.

Sonographic Measurement of the Fetal Iliac Angle Cannot Be Used Alone as a Marker for Trisomy 21

The fetal iliac wings angle was studied in 255 fetuses before amniocentesis at 16.7 weeks (± 1.3), using a sonographic axial view of the fetal pelvis. The measurement could be performed in 208 fetuses (81.6%), of whom 4 had trisomy 21 (T 21). The mean iliac angle was greater in fetuses with T 21 than in normal fetuses (69.8° vs. 88.7°; p = 0.03). This measurement is subject to significant intra- and interexaminer variability (interclass correlation coefficient: 0.65 and 0.23, respectively). When a 90° value is used as a threshold, specificity, sensitivity, positive and negative predictive values are, respectively, 80, 75, 7.0 and 99.4%. The 20% rate of false-positives rules out the use of this measurement as the sole criterion for the indication of amniocentesis for T 21 antenatal diagnosis.