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The "A Randomized Trial of Induction Versus Expectant Management" trial (ARRIVE trial) published in 2018 suggested that induction of labor can be considered a "reasonable option" for low-risk nulliparous women at ≥39 weeks of gestation. The study results led some professional societies to endorse the option for elective induction of labor at 39 weeks of gestation in low-risk nulliparas, and this has begun to change obstetrical practice. The ARRIVE trial provided valuable information supporting the benefits of induction of labor; however, the trial is insufficient to serve as the primary justification for widespread elective induction of labor at 39 weeks of gestation in low-risk nulliparas because of concerns about external validity. Thus, the French ARRIVE trial was designed to test the hypothesis in a different setting that elective induction of labor at 39 weeks of gestation in low-risk nulliparas leads to a lower cesarean delivery rate than expectant management. This ongoing trial has been criticized as "pseudoscientific" and telling "women where, when, and how to give birth." We reject these allegations and extensively examine the ethical framework that should govern clinical and research interventions, including elective induction of labor at 39 weeks of gestation in low-risk nulliparas. This study aimed to discuss the ethical issues that emerge from randomized trials of elective induction of labor at 39 weeks of gestation in low-risk nulliparas and the ethics of the clinical practice itself. The analysis of existing evidence shows the importance of further research on induction of labor at 39 weeks of gestation in low-risk women. Certain aspects of research ethics in this area, particularly the consent of pregnant women in a context where autonomy remains fragile, call for vigilance. In addition, we emphasize that childbirth is not only a medical object but also a social phenomenon that cannot be regarded only from the perspective of a health risk to be managed by clinical research. Further research on this issue is needed to allow pregnant women to make informed decisions, and the results should be integrated with social issues. The perspective of women is required in constructing, evaluating, and implementing medical interventions in childbirth, such as induction of labor at 39 weeks of gestation. [ABSTRACT FROM AUTHOR]

Incontinence occurs frequently in the postpartum period. Several theoretical pathophysiological models may underlie the hypothesis that different types of management of the active phase of the second stage of labor have different effects on pelvic floor muscles and thus perhaps affect urinary and anal continence. This study aimed to evaluate the impact of "moderate pushing" on the occurrence of urinary or anal incontinence compared with "intensive pushing," and to determine the factors associated with incontinence at 6 months postpartum. This was a planned analysis of secondary objectives of the PASST (Phase Active du Second STade) trial, a multicenter randomized controlled trial. PASST included nulliparous women with singleton term pregnancies and epidural analgesia, who were randomly assigned at 8 cm of dilatation to either the intervention group that used "moderate" pushing (pushing only twice during each contraction, resting regularly for 1 contraction in 5 without pushing, and no time limit on pushing) or the control group following the usual management of "intensive" pushing (pushing 3 times during each contraction, with no contractions without pushing, with an obstetrician called to discuss operative delivery after 30 minutes of pushing). Data about continence were collected with validated self-assessment questionnaires at 6 months postpartum. Urinary incontinence was defined by an ICIQ-UI SF (International Consultation on Incontinence Questionnaire–Urinary Incontinence Short Form) score ≥1 and anal incontinence by a Wexner score ≥2. A separate analysis was also performed among the more severely affected women (ICIQ-UI SF ≥6 and Wexner ≥5). Factors associated with incontinence were assessed with univariate and multivariable analyses. Among 1618 women initially randomized, 890 (55%) returned the complete questionnaire at 6 months. The rate of urinary incontinence was 36.6% in the "moderate" pushing group vs 38.5% in the "intensive" pushing group (relative risk, 0.95; 95% confidence interval, 0.80–1.13), whereas the rate of anal incontinence was 32.2% vs 34.6% (relative risk, 0.93; 95% confidence interval, 0.77–1.12). None of the obstetrical factors studied related to the second stage of labor influenced the occurrence of urinary or anal incontinence, except operative vaginal delivery, which increased the risk of anal incontinence (adjusted odds ratio, 1.50; 95% confidence interval, 1.04–2.15). The results of the PASST trial indicate that neither moderate nor intensive pushing efforts affect the risk of urinary or anal incontinence at 6 months postpartum among women who gave birth under epidural analgesia. [ABSTRACT FROM AUTHOR]

Many questions remain about the appropriate use of intrauterine balloon devices in postpartum hemorrhage after vaginal delivery refractory to first-line uterotonics. Available data suggest that early use of intrauterine balloon tamponade might be beneficial. This study aimed to compare the effect of intrauterine balloon tamponade used in combination with second-line uterotonics vs intrauterine balloon tamponade used after the failure of second-line uterotonic treatment on the rate of severe postpartum hemorrhage in women with postpartum hemorrhage after vaginal delivery refractory to first-line uterotonics. This multicenter, randomized, controlled, parallel-group, nonblinded trial was conducted at 18 hospitals and enrolled 403 women who had just given birth vaginally at 35 to 42 weeks of gestation. The inclusion criteria were a postpartum hemorrhage refractory to first-line uterotonics (oxytocin) and requiring a second-line uterotonic treatment with sulprostone (E1 prostaglandin). In the study group, the sulprostone infusion was combined with intrauterine tamponade by an ebb balloon performed within 15 minutes of randomization. In the control group, the sulprostone infusion was started alone within 15 minutes of randomization, and if bleeding persisted 30 minutes after the start of sulprostone infusion, intrauterine tamponade using the ebb balloon was performed. In both groups, if the bleeding persisted 30 minutes after the insertion of the balloon, an emergency radiological or surgical invasive procedure was performed. The primary outcome was the proportion of women who either received ≥3 units of packed red blood cells or had a calculated peripartum blood loss of >1000 mL. The prespecified secondary outcomes were the proportions of women who had a calculated blood loss of ≥1500 mL, any transfusion, an invasive procedure and women who were transferred to the intensive care unit. The analysis of the primary outcome with the triangular test was performed sequentially throughout the trial period. At the eighth interim analysis, the independent data monitoring committee concluded that the incidence of the primary outcome did not differ between the 2 groups and stopped inclusions. After 11 women were excluded because they met an exclusion criterion or withdrew their consent, 199 and 193 women remained in the study and control groups, respectively, for the intention-to-treat analysis. The women's baseline characteristics were similar in both groups. Peripartum hematocrit level change, which was needed for the calculation of the primary outcome, was missing for 4 women in the study group and 2 women in the control group. The primary outcome occurred in 131 of 195 women (67.2%) in the study group and 142 of 191 women (74.3%) in the control group (risk ratio, 0.90; 95% confidence interval, 0.79–1.03). The groups did not differ substantially for rates of calculated peripartum blood loss pf ≥1500 mL, any transfusion, invasive procedure, and admission to an intensive care unit. Endometritis occurred in 5 women (2.7%) in the study group and none in the control group (P =.06). The early use of intrauterine balloon tamponade did not reduce the incidence of severe postpartum hemorrhage compared with its use after the failure of second-line uterotonic treatment and before recourse to invasive procedures. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Although prophylactic tranexamic acid administration after cesarean delivery resulted in a lower incidence of calculated estimated blood loss of >1000 mL or red cell transfusion by day 2, its failure to reduce the incidence of hemorrhage-related secondary clinical outcomes (TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery trial) makes its use questionable. The magnitude of its effect may differ in women at higher risk of blood loss, including those with multiple pregnancies.Objective: This study aimed to compare the effect of tranexamic acid vs placebo to prevent blood loss after cesarean delivery among women with multiple pregnancies.Study Design: This was a secondary analysis of the TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery trial data, a double-blind, randomized controlled trial from March 2018 to January 2020 in 27 French maternity hospitals, that included 319 women with multiple pregnancies. Women with a cesarean delivery before or during labor at ≥34 weeks of gestation were randomized to receive intravenously 1 g of tranexamic acid (n=160) or placebo (n=159), both with prophylactic uterotonics. The primary outcome was a calculated estimated blood loss of >1000 mL or a red blood cell transfusion by 2 days after delivery. The secondary outcomes included clinical and laboratory blood loss measurements.Results: Of the 4551 women randomized in this trial, 319 had a multiple pregnancy and cesarean delivery, and 298 (93.4%) had primary outcome data available. This outcome occurred in 62 of 147 women (42.2%) in the tranexamic acid group and 67 of 152 (44.1%) receiving placebo (adjusted risk ratio, 0.97; 95% confidence interval, 0.68-1.38; P=.86). No significant between-group differences occurred for any hemorrhage-related clinical outcomes: gravimetrically estimated blood loss, provider-assessed clinically significant hemorrhage, additional uterotonics, postpartum blood transfusion, arterial embolization, and emergency surgery (P>.05 for all comparisons).Conclusion: Among women with a multiple pregnancy and cesarean delivery, prophylactic tranexamic acid did not reduce the incidence of any blood loss-related outcomes. [ABSTRACT FROM AUTHOR]

Background: There is no consensus on an optimal strategy for managing the active phase of the second stage of labor. Intensive pushing could not only reduce pushing duration, but also increase abnormal fetal heart rate because of cord compression and reduced placental perfusion and oxygenation resulting from the combination of uterine contractions and maternal expulsive forces. Therefore, it may increase the risk of neonatal acidosis and the need for operative vaginal delivery.Objective: This study aimed to assess the effect of the management encouraging "moderate" pushing vs "intensive" pushing on neonatal morbidity.Study Design: This study was a multicenter randomized controlled trial, including nulliparas in the second stage of labor with an epidural and a singleton cephalic fetus at term and with a normal fetal heart rate. Of note, 2 groups were defined: (1) the moderate pushing group, in which women had no time limit on pushing, pushed only twice during each contraction, and observed regular periods without pushing, and (2) the intensive pushing group, in which women pushed 3 times during each contraction and the midwife called an obstetrician after 30 minutes of pushing to discuss operative delivery (standard care). The primary outcome was a composite neonatal morbidity criterion, including umbilical arterial pH of <7.15, base excess of >10 mmol/L, lactate levels of >6 mmol/L, 5-minute Apgar score of <7, and severe neonatal trauma. The secondary outcomes were mode of delivery, episiotomy, obstetrical anal sphincter injuries, postpartum hemorrhage, and maternal satisfaction.Results: The study included 1710 nulliparous women. The neonatal morbidity rate was 18.9% in the moderate pushing group and 20.6% in the intensive pushing group (P=.38). Pushing duration was longer in the moderate group than in the intensive group (38.8±26.4 vs 28.6±17.0 minutes; P<.001), and its rate of operative delivery was 21.1% in the moderate group compared with 24.8% in the intensive group (P=.08). The episiotomy rate was significantly lower in the moderate pushing group than in the intensive pushing group (13.5% vs 17.8%; P=.02). We found no significant difference for obstetrical anal sphincter injuries, postpartum hemorrhage, or maternal satisfaction.Conclusion: Moderate pushing has no effect on neonatal morbidity, but it may nonetheless have benefits, as it was associated with a lower episiotomy rate. [ABSTRACT FROM AUTHOR]

Background: Placenta accreta spectrum is a life-threatening condition that has increased dramatically in recent decades along with cesarean rates worldwide. Cesarean hysterectomy is widely practiced in women with placenta accreta spectrum; however, the maternal outcomes after cesarean hysterectomy have not been thoroughly compared with the maternal outcomes after alternative approaches, such as conservative management.Objective: This study aimed to compare the severe maternal outcomes between women with placenta accreta spectrum treated with cesarean hysterectomy and those treated with conservative management (leaving the placenta in situ).Study Design: From a source population of 520,114 deliveries in 176 hospitals (PACCRETA study), we designed an observational cohort of women with placenta accreta spectrum who had either a cesarean hysterectomy or a conservative management (the placenta left in situ) during cesarean delivery. Clinicians prospectively identified women meeting the inclusion criteria and included them at delivery. Data collection started only after the women had received information and agreed to participate in the study in the immediate postpartum period. The primary outcome was the transfusion of >4 units of packed red blood cells within 6 months after delivery. Secondary outcomes were other maternal complications within 6 months. We used propensity score weighting to account for potential indication bias.Results: Here, 86 women had conservative management and 62 women had cesarean hysterectomy for placenta accreta spectrum during cesarean delivery. The primary outcome occurred in 14 of 86 women in the conservative management group (16.3%) and 36 of 61 (59.0%) in the cesarean hysterectomy group (risk ratio in propensity score weighted model, 0.29; 95% confidence interval, 0.19-0.45). The rates of hysterectomy, total estimated blood loss exceeding 3000 mL, any blood product transfusion, adjacent organ injury, and nonpostpartum hemorrhage-related severe maternal morbidity were lower with conservative management than with cesarean hysterectomy (all adjusted, P≤.02); but, the rates of arterial embolization, endometritis, and readmission within 6 months of discharge were higher with conservative management than with cesarean hysterectomy.Conclusion: Among women with placenta accreta spectrum who underwent cesarean delivery, conservative management was associated with a lower risk of transfusion of >4 units of packed red blood cells within 6 months than cesarean hysterectomy. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The North Paris community-based Perinatal Network was set up in 2003 to improve the quality of prenatal care in an area surrounding the Bichat Claude Bernard University Hospital characterized by high social deprivation. The aim of this study is to assess the impact of the network on early perinatal care. Materials and methods: A retrospective observational study on medical records was conducted over four periods: one year before the setting up of the network (2002), the year the network became operational (2003), and one year (2004) and five years (2008) after implementation. Endpoints were the proportion of women delivered in the institution who underwent first-trimester ultrasound screening and the proportion of nuchal translucency measurements deemed acceptable (image quality score from 4 to 9 according to the Herman scoring system). Results: Between 2002 and 2004, substantial improvements were noted in access to first-trimester ultrasound screening (55.8% in 2002, 65.9% in 2003, 71.9% in 2004, P <0.05) and in the quality of nuchal translucency measurement (acceptable measurement over this period, 51.1%, 67.8% and 77.8%, respectively, P <0.001). Five years after network set-up, indicators remained unchanged from those of 2004. The rate of first ultrasound screening performed was 72.1% and the rate of acceptable measurement 71.1%, both non-statistically different from 2004 rates. Conclusion: This perinatal network seems to be associated with an improvement in early prenatal care. However, the rate of first ultrasound performed remained unsatisfactory and to further improve these indicators, upstream social interventions are needed. [Copyright &y& Elsevier]

Summary: Background & aims: Infants born with severe IUGR are exposed to higher neonatal mortality and morbidity rates, as compared with appropriate-for-gestational-age. They are exposed to a higher risk of developing chronic disease such as hypertension, coronary artery disease, obesity, and type 2 diabetes in adulthood. l-Arginine is a precursor of nitric oxide (NO) and may play a role in placental vascular mediation or local vasodilatation. Objective: The current study was designed to determine whether oral supplementation of gravid patients suffering from severe intrauterine growth restriction (IUGR) with l-arginine, would enhance birth weight and/or decrease neonatal morbidity. Patients and methods: Forty-four patients with a singleton pregnancy who had been referred for IUGR detected by ultrasonic examination were included. Vascular IUGR was defined by fetal abdominal circumference less than or equal to the 3rd percentile, associated with abnormal uterine Doppler. After double-blind randomization, patients received either 14g/day of l-arginine, or a placebo. Results: The characteristics of the two groups of patients (IUGR with l-arginine vs IUGR with placebo) were similar upon randomization. There was no significant difference between the two groups concerning birth weight (1042±476 vs. 1068±452g). At delivery, maternal and neonatal characteristics were similar in the two groups. There was no difference in the Clinical Risk Index for Babies (CRIB) score, the duration of ventilatory assistance, nor the delay between birth and full enteral feeding between the two groups. Conclusion: In this study which is, at the best of our knowledge, the first double-bind, multicenter, randomized trial in this condition, l-arginine is not an effective treatment for severe vascular growth restriction. [Copyright &y& Elsevier]

Objective Data from the international literature suggest that there may be an association between maternal human immunodeficiency virus (HIV) infection and vasculoplacental complications during pregnancy. Studies on this subject have reached discordant conclusions. The aim of this study was to assess the incidence of vasculoplacental complications during pregnancy in women with and without HIV infection. Study Design This single-center case-control study compared the incidence of pregnancy-related hypertension, preeclampsia, eclampsia, and vascular intrauterine growth restriction in 280 women with HIV and 560 women not infected with HIV, matched for age, parity, and geographic origin. Results The incidence rates of pregnancy-related hypertension, preeclampsia, eclampsia, and vascular growth restriction did not differ between the women with and without HIV infection. The overall incidence of vasculoplacental complications did not differ between the 2 groups (7.5% vs 9.8%, respectively; P = .27). The risk of these was not associated with exposure to antiretroviral treatments, viral load, or CD4 T-cell counts at the beginning of pregnancy. Conclusion This study shows no difference in the incidence of vasculoplacental complications between women with and without HIV infection. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Elective cesarean section (CS) is a proven method to prevent mother-to-child transmission (MTCT), but is no longer recommended for women with antiretroviral therapy resulting in a low viral load (VL): <400 copies/mL in French and <1000 copies/mL in US guidelines. We sought to describe mode of delivery practices in human immunodeficiency virus (HIV)-infected women and their association with MTCT and postpartum complications. STUDY DESIGN: All deliveries from HIV-1-infected women in the French Perinatal Cohort (Agence Nationale de Recherches sur le Sida/Enquête Périnatale Française) 2000 through 2010 (N = 8977) were analyzed, with additional details for 2005 through 2010 (n = 4717). RESULTS: Vaginal deliveries increased from 25% in 2000 to 53% in 2010. Over 2005 through 2010, 4300 women had VL before delivery <400 copies/mL; among them only 49.3% delivered vaginally, 22.0% had nonelective CS, and 28.7% had elective CS. Elective CS were performed for scarred uterus in 45.4%, other obstetrical indications in 37.1%, and solely because of HIV in 15.7%. Of the 417 women with VL >=400 copies/mL, 48.9% had elective CS as recommended, 25.9% had nonelective CS, and 25.2% had vaginal delivery. The MTCT rate did not differ according to the mode of delivery in term deliveries (>=37 gestational weeks) in 2000 through 2010: 0.3% after both vaginal delivery and elective CS with VL <50 copies/mL, 4.0% vs 5.3%, respectively, with VL >=10,000 copies/mL. In case of preterm delivery, MTCT rates tended to be higher with vaginal delivery. Postpartum complications were more frequent following CS than vaginal deliveries (6.5% vs 2.9, P < .01). CONCLUSION: Our findings suggest that HIV-infected women on antiretroviral therapy with low VL can safely opt for vaginal delivery in the absence of obstetrical risk factors. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to evaluate the efficacy of maternal serum markers in detecting Down syndrome after 18 weeks of gestation in women who book late for maternity care in a large national retrospective study. Study Design: During the period 2007-2012, 27,648 women, regardless of maternal age (17.4% were 35 years old and over), were included in a late Down syndrome screening program (18+0 to 35+6 weeks) using the maternal serum markers alpha-fetoprotein and human chorionic gonadotrophin-beta. Samples were assayed in a single laboratory. A dataset of median markers previously established in our laboratory was used for risk calculation. The control group consisted of 27,648 women (14+0 to 17+6 weeks) randomly selected from the routine database. Results: When the later screening group was compared with the standard second-trimester control group, the median multiples of medians (1.01 vs 0.98 for alpha-fetoprotein, 1.03 vs 0.98 for human chorionic gonadotrophin-beta), median risks (1 of 2414 vs 1 of 2720), false-positive rates (11.1% vs 11.6%), and trisomy 21 detection rates (83.3% vs 85.7%) did not differ significantly. Conclusion: Late Down syndrome maternal serum screening is feasible with a good sensitivity/specificity compromise throughout gestation and is of clinical value in late-booking women. [ABSTRACT FROM AUTHOR]

Objective: We sought to identify factors associated with adverse perinatal outcomes (APO) among term breech neonates with planned vaginal deliveries. Study Design: We conducted univariable and multilevel multivariable analysis of the data collected in the multicenter prospective observational study PREsentation et MODe d''Accouchement (PREMODA) in women with planned vaginal delivery giving birth to singleton term breech babies. The end point was a composite set of APO. Results: Of 2502 women with planned vaginal delivery recruited in the 174 participating centers, 1772 (71%) delivered vaginally. Adverse outcomes were observed in 165 cases (6.59%). After adjustment, the factors associated with them were geographic origin, gestational age <39 weeks at birth, birthweight <10th percentile, and annual number of maternity unit births <1500. Conclusion: When strict conditions governed the selection of delivery route and management of labor was rigorous, APO were not associated with any prenatal or peripartum obstetric factors. [Copyright &y& Elsevier]

Objective: The objective of the study was to evaluate the use of 17 alpha-hydroxyprogesterone caproate (17P) to reduce preterm delivery. Study Design: This open-label, multicenter, randomized controlled trial included women with singleton pregnancies admitted at 24-31 weeks'' gestation and cervical length less than 25 mm for preterm labor successfully arrested by tocolytic treatment. Randomization assigned them to receive (or not) 500 mg of intramuscular 17P after tocolysis ended, repeated semiweekly until 36 weeks or preterm delivery. The primary outcome was the time from randomization to delivery. Results: Outcome data were available for 184 of 188 women randomized. The 17P and control groups (similar for most baseline characteristics) did not differ significantly for median [interquartile range] time to delivery (64 [42–79] and 67 [46–83] days, respectively) or rates of delivery before 37, 34, or 32 weeks of gestation or adverse perinatal outcomes. Conclusion: Semiweekly injections of 17P did not prolong pregnancy significantly in women with tocolysis-arrested preterm labor. [Copyright &y& Elsevier]

Background: Disparities in neuraxial analgesia use for childbirth by maternal origin have been reported in high-resource countries. We explored the association between maternal immigrant status (characterised separately by geographic continental origin and Human Development Index [HDI] of maternal country of birth) and neuraxial analgesia use. We hypothesised that immigrant women from low-resource countries may have more limited access to neuraxial analgesia than native French women.Methods: The study population, extracted from the 2016 National Perinatal Survey, a cross-sectional study of a representative sample of births in France, included only women who initially wished to deliver with neuraxial analgesia. We used multivariable multilevel logistic regression to explore the association between immigrant status and both use of neuraxial analgesia and its timely administration.Results: Among the 6070 women included, 88.1% gave birth with neuraxial analgesia and 15.8% were immigrants. There was no difference in neuraxial analgesia use between native French women and either immigrant women by geographic continental region of origin, or immigrants from countries with low HDI. However, immigrants from countries with very high HDI were more likely to give birth with neuraxial analgesia (adjusted odds ratio [aOR]=2.6; 95% confidence interval (CI), 1.2-5.8; P=0.018) and its timeliness <60 min after admission (aOR=1.8; 95% CI, 1.2-2.7; P=0.005) compared with native French women.Conclusions: In France, immigrant women from low-resource countries have similar access to labour neuraxial analgesia to native French women. Our results suggest differential neuraxial analgesia use in favour of immigrant women from very high HDI countries compared with native women. [ABSTRACT FROM AUTHOR]

This systematic review seeks to evaluate the efficacy of interventions aimed at preventing unintended pregnancies in women using psychoactive substances. Seven electronic databases (Medline, EMBASE, CINAHL, Web of Science Core Collection, PsycINFO, Cochrane CENTRAL database) were searched in October 2017. Twenty-two articles met our inclusion criteria. Interventions based on behavior change theory yielded an increase in the initiation of effective contraception as compared with provision of written information materials. The effect was more pronounced when the intervention provided on-site contraceptive counseling and free access to birth control. Financial incentives also seemed to effectively increase women's contraception intake. Case management interventions including pregnant and postpartum women with heavy levels of substance use showed promising results in terms of initiation of contraception, but rates of unintended pregnancy over long-term follow-up were nevertheless elevated. Finally, some interventions integrated family planning services into specialized centers taking care of pregnant and postpartum women with substance abuse. However, most studies aimed at postpartum and post-abortion contraception used a non-comparative design and had a number of methodological flaws. The risk of bias in most studies is high. All interventions with a primary or secondary focus on the prevention of unintended pregnancy in women using psychoactive substances short-term improvements in contraception intake, but it is unclear if these effects last or have any impact on unintended pregnancy rates in the long-term. [ABSTRACT FROM AUTHOR]

Proximal 19p13.12 microdeletion has been rarely reported. Only five postnatal cases with intellectual disability, facial dysmorphism, branchial arch defects and overlapping deletions involving proximal 19p13.12 have been documented. Two critical intervals were previously defined: a 700 kb for branchial arch defects and a 350 kb for hypertrichosis-synophrys-protruding front teeth. We describe the first prenatal case, a fetal death in utero at 39 weeks of gestation. Agilent 180K array-CGH analysis identified a heterozygous interstitial 745 kb deletion at 19p13.12 chromosome region, encompassing both previously reported critical intervals, including at least 6 functionally relevant genes: NOTCH3 , SYDE1 , AKAP8 , AKAP8L , WIZ and BRD4 . Quantitative PCR showed that the deletion occurred de novo with a median size of 753 kb. NOTCH3 and SYDE1 were candidate genes for placental pathology whilst AKAP8 , AKAP8L , WIZ and BRD4 were highly expressed in the branchial arches. Molecular characterization and sequencing of candidate genes for placental pathology and branchial arch defects were carried out in order to correlate the genotype-phenotype relationship and unravel the underlying mechanism of proximal 19p13.12 microdeletion syndrome. This case also contributes to define the novel critical interval and expand the clinical phenotype spectrum of proximal 19p13.12 microdeletion syndrome. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To assess the impact of extreme preterm premature rupture of membranes (PPROM) <25 weeks of gestation on preterm child outcome. Study design: Retrospective study comparing the neonatal and 2-year outcomes of infants exposed to extremely PPROM <25 weeks with a non-exposed group of neonates in a tertiary care referral centre located in Paris, France, between 2003 and 2007. All women with singleton pregnancy and PPROM between 150/7 and 246/7 weeks of gestation were recruited. For each infant born alive, the next inborn neonate matched for gestational age and sex was selected as a control among neonates born alive after spontaneous preterm labour with intact membranes. The main outcome measures were neonatal outcome assessed by a combined criterion of adverse neonatal outcomes and the two-year neurodevelopmental outcome assessed by developmental Brunet–Lézine tests and neurological examinations. Results: In 78 cases of extremely PPROM, 22 live births occurred at a mean gestational age of 265/7 weeks. The percentage of neonates with adverse neonatal outcomes was significantly higher among PPROM than non-exposed cases (68.2 versus 27.3%). At 2 years of age, children from the PPROM group were more likely to have delayed acquisitions (64.3 versus 15.8%) and behavioural disorders (57.1 versus 15.8%). Mean Brunet–Lézine language score was significantly lower among those infants (78.9 versus 96.8). Conclusion: PPROM <25 weeks is associated with increased neonatal mortality and morbidity and with increased risks of delayed acquisitions, behavioural disorders and lower language performance scores at 2 years in comparison with matched preterm neonates born after spontaneous preterm labour with intact membranes. [Copyright &y& Elsevier]

Abstract: Objective: To study the impact on the neonate of maternal antiretroviral therapy with atazanavir (ATV). Study design: An observational study of 22 HIV-infected women receiving, for clinical indications, antiretroviral therapy with ATV 300mg and ritonavir 100mg during pregnancy and their 23 HIV infants (including a twin pair). Results: Mothers had received ATV for a median duration of 19 months [range 3–49] by delivery. At delivery, plasma HIV-RNA was <40copies/mL in all patients. Liver enzymes were normal in 19/22 patients, but one woman had grade 3–4 liver toxicity. Maternal serum bilirubin concentrations were above the upper limit of normal in most patients, with grade 3 toxicity in 5 patients. All but one woman had trough ATV concentrations during pregnancy above the minimum effective concentration. The median cord blood ATV concentration was 130ng/mL [range <30–758]; the cord/maternal ratio was 21%. All neonates were born at term [median 38.2 weeks]. Three neonates had mildly elevated AST transaminase levels. Bilirubin concentrations at birth were significantly higher than maternal concentrations, with a median of 44μm/L [range 24–129]; values on days 2–3 were 63 [8–212]. Five neonates had jaundice requiring phototherapy, without liver damage, and recovered without sequelae. Conclusion: Neonates whose mothers were treated with ATV should be monitored for hyperbilirubinemia, which may be due to placental transfer of unconjugated bilirubin from the mother and/or a direct effect of transplacental ATV on bilirubin metabolism in the fetus. [Copyright &y& Elsevier]