Diabetic acidosis with severe fetal hypoxia in pregnancy: Narrative review and case study.

Diabetic ketoacidosis (DKA) in pregnancy could be a disastrous event with increased maternal and perinatal morbidity and mortality. DKA can occur with a normal blood glucose level, known as euglycemic DKA. It particularly affects pregnant women with type I diabetes. Here, we report the case of a 28 year-old primigravid patient, with a diagnosis of type 1 diabetes for 8 years. This patient consulted our department at 29 weeks of gestation with a previous history of headaches, vomiting and diarrhea for 9 h. Blood glucose level was 8.8 mmol/L with a ketone test positive (>15 mg/dL). Blood test showed high anion gap (17.9 mmol/L) with low serum bicarbonate rate (21 mmol/L). Systemic examination and fetal heart rate (FHR) was reassuring. The patient was subsequently discharged. She returned to the clinic 19 h later with further symptoms of nausea, polyuria-polydipsia, asthenia and a weight loss of 4 kg since the day before. Blood sugar was 14.3 mmol/L and a ketone test was strongly positive. Cardiotocography showed fetal tachycardia and repeated late decelerations. A diagnosis of DKA was made and emergency cesarean was performed for fetal distress. At delivery, pH was acidosis (pH: 7.02, lactates: 6.2). The patient was successfully treated with intravenous hydration and insulin. Neonatal evolution was favorable. Pregnant women with type I diabetes can develop euglycemic DKA. Early recognition and prompt treatment could help prevent severe maternal and fetal adverse outcomes. DKA in pregnant women can induce fetal acidosis with abnormal FHR. In this situation, a cesarean can be performed to improve neonatal outcome even inducing a premature delivery. Prolonged pregnancy can lead to irreversible neonatal brain abnormalities.

Obstetric and haematological management and outcomes of women with placenta accreta spectrum by planned or urgent delivery: Secondary data analysis of a public referral hospital in Lebanon.

BACKGROUND: Lebanon has a high caesarean section use and consequently, placenta accreta spectrum (PAS) is becoming more common. OBJECTIVES: To compare maternal characteristics, management, and outcomes of women with PAS by planned or urgent delivery at a major public referral hospital in Lebanon. DESIGN: Secondary data analysis of prospectively collected data. SETTING: Rafik Hariri University Hospital (public referral hospital), Beirut, Lebanon. PARTICIPANTS: 159 pregnant and postpartum women with confirmed PAS between 2007-2020. MAIN OUTCOME MEASURES: Maternal characteristics, management, and maternal and neonatal outcomes. RESULTS: Out of the 159 women with PAS included, 107 (67.3%) underwent planned caesarean delivery and 52 (32.7%) had urgent delivery. Women who underwent urgent delivery for PAS management were more likely to experience antenatal vaginal bleeding compared to those in the planned group (55.8% vs 28.0%, p<0.001). Median gestational age at delivery was significantly lower for the urgent group compared to the planned (34 vs. 36 weeks, p<0.001). There were no significant differences in terms of blood transfusion rates and major maternal morbidity between the two groups; however, median estimated blood loss was significantly higher for women with urgent delivery (1500ml vs. 1200ml, p = 0.011). Furthermore, the urgent delivery group had a significantly lower birth weight (2177.5g vs. 2560g, p<0.001) with higher rates of neonatal intensive care unit (NICU) admission (53.7% vs 23.8%, p<0.001) and perinatal mortality (18.5% vs 3.8%, p = 0.005). CONCLUSION: Urgent delivery among women with PAS is associated with worse maternal and neonatal outcomes compared to the planned approach. Therefore, early referral of women with known or suspected PAS to specialized centres is highly desirable to maximise optimal outcomes for both women and infants.

Risk factors for placenta accreta spectrum disorders in women with any prior cesarean and a placenta previa or low lying: a prospective population-based study.

This study aimed to identify the risk factors for placenta accreta spectrum (PAS) in women who had at least one previous cesarean delivery and a placenta previa or low-lying. The PACCRETA prospective population-based study took place in 12 regional perinatal networks from 2013 through 2015. All women with one or more prior cesareans and a placenta previa or low lying were included. Placenta accreta spectrum (PAS) was diagnosed at delivery according to standardized clinical and histological criteria. Of the 520,114 deliveries, 396 fulfilled inclusion criteria; 108 were classified with PAS at delivery. Combining the number of prior cesareans and the placental location yielded a rate ranging from 5% for one prior cesarean combined with a posterior low-lying placenta to 63% for three or more prior cesareans combined with placenta previa. The factors independently associated with PAS disorders were BMI ≥ 30, previous uterine surgery, previous postpartum hemorrhage, a higher number of prior cesareans, and a placenta previa. Finally, in this high-risk population, the rate of PAS disorders varies greatly, not only with the number of prior cesareans but also with the exact placental location and some of the women's individual characteristics. Risk stratification is thus possible in this population.

Maternal and neonatal outcomes of French prospective multicenter cohort study COVIPREG during the first two COVID-19 waves.

BACKGROUND: SARS-CoV-2 infection on pregnant women was the subject of many questions since the COVID-19 pandemic. METHODS: We aim to assess maternal and neonatal outcomes of SARS-CoV-2 infection contracted during 2nd and 3rd trimesters of pregnancy during the first two COVID-19 waves across a prospective French multicenter cohort study. Patients were included between April 2020 and January 2021 in 10 maternity hospitals in Paris area with two groups (i) pregnant women with a positive SARS-CoV-2 nasopharyngeal RT-PCR between [14WG; 37WG[(symptomatic infection), (ii) pregnant women with a negative serology (or equivocal) at delivery and without a positive SARS-CoV-2 nasopharyngeal RT-PCR at any time during pregnancy (G2 group) MAIN FINDINGS: 2410 pregnant women were included, of whom 310 had a positive SARS-CoV-2 nasopharyngeal RT-PCR and 217 between [14WG; 37WG[. Most infections occurred between 28 and 37 weeks of gestation (56 %). Most patients could be managed as outpatients, while 23 % had to be hospitalized. Among women with a positive RT-PCR, multiparous women were over-represented (OR = 2.45[1.52;3.87]); were more likely to deliver before 37 weeks of gestation (OR = 2.19[1.44;3.24]) and overall cesarean deliveries were significantly increased (OR = 1.53[1.09;2.13]). CONCLUSIONS: This study highlights the maternal, obstetrical, and neonatal burden associated with SARS-CoV-2 infections during the first two pandemic waves before availability of vaccines. TRIAL REGISTRATION: NCT04355234 (registration date: 21/04/2020).

[Investigation of a French cohort of neonatal anoxo-ischemic encephalopathy in the era of therapeutic hypothermia: Questions and answers]. / Analyse d'une cohorte française d'encéphalopathies néonatales anoxo-ischémiques à l'ère de l'hypothermie thérapeutique : questions­réponses.

OBJECTIVE: To improve knowledge of neonatal hypoxic-ischemic encephalopathy, a prospective, nationwide, population-based cohort of affected children is being set up between September 2015 and March 2017. METHODS: During this period, 794 cases are collected, with information on pregnancy, delivery, neonatal stay and outcome at the end of hospitalization. Clinical and parental questionnaire follow-up is planned until the child is 4 years old. RESULTS: This article presents the clinical presentation of the newborns included, the analysis of factors associated with short-term outcome at hospital discharge and the organizational factors associated with treatment with therapeutic hypothermia. CONCLUSION: These data illustrate the value of a prospective cohort to analyze the management of anoxo-ischemic encephalopathy in France.

Birth weight and head circumference discordance and outcome in preterms: results from the EPIPAGE-2 cohort.

OBJECTIVE: To determine whether the relative measurement of birth weight (BW) and head circumference (HC) in preterm infants is associated with neurological outcomes. METHODS: The EPIPAGE-2 Study included 3473 infants born before 32 weeks' gestation, classified based on their Z-score of BW and HC on the Fenton curves as concordant (≤1 SD apart) or discordant (>1 SD difference). We defined four mutually exclusive categories: discordant smaller BW (sBW) with BW-1SD and concordant small measurement (CsM) with BW and HC concordant and both ≤-1SD. Neurological outcomes at 5.5 years were evaluated with standard tests. RESULTS: 2592 (74.8%) preterm neonates were categorised as CM, 258 (7.4%) CsM, 378 (10.9%) sHC and 239 (6.9%) sBW. Compared with the CM children, those born with CsM had significantly higher risks of cognitive deficiency (adjusted OR (aOR) 1.3, 95% CI (1.0 to 2.0)), developmental coordination disorders (aOR 2.6 (1.5 to 4.4)) and need for special school services (aOR 2.3 (1.5 to 3.7)). Those born with sBW had significantly lower risk of cognitive deficiency (aOR 0.6 (0.4 to 0.9)) and the sHC group significantly higher risk of developmental coordination disorders (aOR 1.8 (1.0 to 3.2)). CONCLUSIONS: The relative discordance of these preterm infants' BW and HC was associated with their neurological outcomes. It merits further exploration as an indirect indicator of development. TRIAL REGISTRATION NUMBER: NCT03078439.

Clinical Chorioamnionitis and Neurodevelopment at 5 Years of Age in Children Born Preterm: The EPIPAGE-2 Cohort Study.

OBJECTIVE: To assess the association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born preterm. STUDY DESIGN: EPIPAGE 2 is a national, population-based cohort study of children born before 35 weeks of gestation in France in 2011. We included infants born alive between 240/7 and 346/7 weeks after preterm labor or preterm premature rupture of membranes. Clinical chorioamnionitis was defined as maternal fever before labor (>37.8°C) with ≥2 of the following criteria: maternal tachycardia, hyperleukocytosis, uterine contractions, purulent amniotic fluid, or fetal tachycardia. The primary outcome was a composite, including cerebral palsy, coordination disorders, cognitive disorders, sensory disorders, or behavioral disorders. We also analyzed each of these disorders separately as secondary outcomes. We performed a multivariable analysis using logistic regression models. We accounted for the nonindependence of twins and missing data by generalized estimating equation models and multiple imputations, respectively. RESULTS: Among 2927 children alive at 5 years of age, 124 (3%) were born in a context of clinical chorioamnionitis. Overall, 8.2% and 9.6% of children exposed and unexposed, respectively, to clinical chorioamnionitis had moderate-to-severe neurodevelopmental disorders. After multiple imputations and multivariable analysis, clinical chorioamnionitis was not associated with the occurrence of moderate-to-severe neurodevelopmental disorders (aOR, 0.9; 95% CI, 0.5-1.8). CONCLUSIONS: We did not find any association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born at <35 weeks of gestation after preterm labor or preterm premature rupture of membrane.

Massive perivillous fibrin deposition: Diagnosis, obstetrical features, and treatment.

MPVFD (Massive perivillous fibrin deposition) is placental lesion characterized by extensive massive deposits of fibrin in the intervillous space, extending over at least 25 % of the placental volume. Currently, this pathology can only be detected through histopathological examination of the placenta after a pregnancy has ended. The underlying mechanisms are poorly studied, there is no biomarker available for the diagnosis of MPVFD and treatment protocols are experimental and still lacking. The objective of this study is to systematically review the literature on the associated clinicopathologic features, treatment, and prognosis of MPVFD. We ended up with 17 studies, of these 12 studies were considered relevant for this article and included in the final analysis. All studies reporting MPVFD are retrospective. MPVFD is associated with recurrent miscarriage, intra uterine fetal death (IUFD), intra uterine growth restriction (IUGR) and preterm delivery. The prevalence in pregnancies with a delivery after 22 weeks of gestation was at 1.1 % and even higher to 2.7 % in recurrent early miscarriages. The reported risk of fetal death in MPVFD ranges mainly from 15 to 80 %. Preterm delivery is spontaneous in 50 to 70 % of cases and induced by of a severe intrauterine growth restriction (IUGR) in 30 to 50 % of cases depending on the study. Its causes and treatment are still poorly understood, although several avenues have been explored. This review summarizes current understanding of the prevalence, diagnostic features, clinical consequences, immune pathology, and potential prophylaxis against recurrence in this chronic inflammatory placental syndrome.

Impact of discontinuing oxytocin in active labour on neonatal morbidity: an open-label, multicentre, randomised trial.

BACKGROUND: Oxytocin is effective in reducing labour duration but can be associated with fetal and maternal complications that could potentially be reduced by discontinuing the treatment during labour. We aimed to assess the impact of discontinuing oxytocin during active labour on neonatal morbidity. METHODS: STOPOXY was a multicentre, randomised, open-label, controlled, superiority trial conducted in 21 maternity units in France. Participants who received oxytocin before 4 cm dilation were randomly assigned 1:1 to either discontinuous oxytocin (oxytocin infusion stopped beyond a cervical dilation equal to or greater than 6 cm) or continuous oxytocin (administration of oxytocin continued until delivery). Randomisation was stratified by centre and parity. The primary outcome, neonatal morbidity, was assessed at birth using a composite variable defined by an umbilical arterial pH at birth less than 7·10, a base excess greater than 10 mmol/L, umbilical arterial lactates greater than 7 mmol/L, a 5-min Apgar score less than 7, or admission to the neonatal intensive care unit. Efficacy and safety was assessed in participants who were randomly assigned (excluding those who withdrew consent or were deemed ineligible after randomisation) and had reached a cervical dilation of at least 6 cm. This trial is registered with ClinicalTrials.gov, NCT03991091. FINDINGS: Of 2459 participants randomly assigned between Jan 13, 2020, and Jan 24, 2022, 2170 were eligible to receive the intervention and were included in the final modified intention-to-treat analysis. The primary outcome occurred for 102 (9·6%) of 1067 participants (95% CI 7·9 to 11·5) in the discontinuous oxytocin group and for 101 (9·2%) of 1103 participants (7·6 to 11·0) in the continuous oxytocin group; absolute difference 0·4% (95% CI -2·1 to 2·9); relative risk 1·0 (95% CI 0·8 to 1·4). There were no clinically significant differences in adverse events between the two groups of the safety population. INTERPRETATION: Among participants receiving oxytocin in early labour, discontinuing oxytocin when the active phase is reached does not clinically or statistically significantly reduce neonatal morbidity compared with continuous oxytocin. FUNDING: French Ministry of Health and the Département de la Recherche Clinique et du Développement de l'Assistance Publique-Hôpitaux de Paris.

Tocolysis after preterm prelabor rupture of membranes and 5-year outcomes: a population-based cohort study.

BACKGROUND: The administration of tocolytics after preterm prelabor rupture of membranes remains a controversial practice. In theory, reducing uterine contractility should delay delivery and allow for optimal antenatal management, thereby reducing the risks for prematurity and adverse consequences over the life course. However, tocolysis may be associated with neonatal death or long-term adverse neurodevelopmental outcomes, mainly related to prolonged fetal exposure to intrauterine infection or inflammation. In a previous study, we showed that tocolysis administration was not associated with short-term benefits. There are currently no data available to evaluate the impact of tocolysis on neurodevelopmental outcomes in school-aged children born prematurely in this clinical setting. OBJECTIVE: This study aimed to investigate whether tocolysis administered after preterm prelabor rupture of membranes is associated with neurodevelopmental outcomes at 5.5 years of age. STUDY DESIGN: We used data from a prospective, population-based cohort study of preterm births recruited in 2011 (referred to as the EPIPAGE-2 study) and for whom the results of a comprehensive medical and neurodevelopmental assessment of the infant at age 5.5 years were available. We included pregnant individuals with preterm prelabor rupture of membranes at 24 to 32 weeks' gestation in singleton pregnancies with a live fetus at the time of rupture, birth at 24 to 34 weeks' gestation, and participation of the infant in an assessment at 5.5 years of age. Exposure was the administration of any tocolytic treatment after preterm prelabor rupture of membranes. The main outcome was survival without moderate to severe neurodevelopmental disabilities at 5.5 years of age. Secondary outcomes included survival without any neurodevelopmental disabilities, cerebral palsy, full-scale intelligence quotient, developmental coordination disorders, and behavioral difficulties. A propensity-score analysis was used to minimize the indication bias in the estimation of the treatment effect on outcomes. RESULTS: Overall, 596 of 803 pregnant individuals (73.4%) received tocolytics after preterm prelabor rupture of membranes. At the 5.5-year follow-up, 82.7% and 82.5% of the children in the tocolysis and no tocolysis groups, respectively, were alive without moderate to severe neurodevelopmental disabilities; 52.7% and 51.1%, respectively, were alive without any neurodevelopmental disabilities. After applying multiple imputations and inverse probability of treatment weighting, we found no association between the exposure to tocolytics and survival without moderate to severe neurodevelopmental disabilities (odds ratio, 0.93; 95% confidence interval, 0.55-1.60), survival without any neurodevelopmental disabilities (odds ratio, 1.02; 95% confidence interval, 0.65-1.61), or any of the other outcomes. CONCLUSION: There was no difference in the neurodevelopmental outcomes at age 5.5 years among children with and without antenatal exposure to tocolysis after preterm prelabor rupture of membranes. To date, the health benefits of tocolytics remain unproven, both in the short- and long-term.

[Induced abortion between 14 and 16th: Clinical context and complications]. / Étude prospective sur 46 patientes de la pratique de l'IVG chirurgicale entre 14 et 16 SA : parcours de soins et complications.

OBJECTIVE: This study aims to characterize the women's health care pathway and to evaluate the rate of complications during a surgical abortion according to the technique of dilatation and evacuation between 14 and 16 SA. METHOD: Single-center prospective study at the Armand Trousseau Hospital with inclusion of women who had an abortion between 14 and 16 GA in the Obstetrics & Gynecology Department of the Armand Trousseau Hospital between March 2 and October 31, 2022. RESULTS: Forty-six women underwent an abortion during this 8-month period. The average gestational age at which the abortions were performed was 15 weeks' gestation with an median delay of 14.0 days between the date of discovery of the pregnancy and the date of the abortion with more than half of the women (65.2 %, N=30) having consulted for the first time for an abortion request before 14 weeks' gestation. Of these women, 22 (48.9%) had to consult several hospitals before being treated. One woman (2.2% 95% CI [0.0-6.4]) had a haemorrhage defined by bleeding more than 500ml. Cervical suture for cervical tear was performed in four women (8.7% 95% CI [0.0-16.8]). There were no complications such as perforation, postoperative infection or surgical revision. No women were transfused. CONCLUSION: The introduction in our center of surgical abortion using the dilatation and evacuation technique performed between 14 and 16 weeks' gestation wasn't accompanied by significant morbidity. The women's pathway before the procedure probably contributed to the later performance of the abortion.

Moderate or intensive management of the active phase of second-stage labor and risk of urinary and anal incontinence: results of the PASST randomized controlled trial.

BACKGROUND: 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. OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: 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.

Effectiveness and Costs of Molecular Screening and Treatment for Bacterial Vaginosis to Prevent Preterm Birth: The AuTop Randomized Clinical Trial.

Importance: Bacterial vaginosis (BV) is a well-known risk factor for preterm birth. Molecular diagnosis of BV is now available. Its impact in the screening and treatment of BV during pregnancy on preterm births has not been evaluated to date. Objective: To evaluate the clinical and economic effects of point-of-care quantitative real-time polymerase chain reaction screen and treat for BV in low-risk pregnant women on preterm birth. Design, Setting, and Participants: The AuTop trial was a prospective, multicenter, parallel, individually randomized, open-label, superiority trial conducted in 19 French perinatal centers between March 9, 2015, and December 18, 2017. Low-risk pregnant women before 20 weeks' gestation without previous preterm births or late miscarriages were enrolled. Data were analyzed from October 2021 to November 2022. Interventions: Participants were randomized 1:1 to BV screen and treat using self-collected vaginal swabs (n = 3333) or usual care (n = 3338). BV was defined as Atopobium vaginae (Fannyhessea vaginae) load of 108 copies/mL or greater and/or Gardnerella vaginalis load of 109 copies/mL or greater, using point-of-care quantitative real-time polymerase chain reaction assays. The control group received usual care with no screening of BV. Main Outcomes and Measures: Overall rate of preterm birth before 37 weeks' gestation and total costs were calculated in both groups. Secondary outcomes were related to treatment success as well as maternal and neonate health. Post hoc subgroup analyses were conducted. Results: Among 6671 randomized women (mean [SD] age, 30.6 [5.0] years; mean [SD] gestational age, 15.5 [2.8] weeks), the intention-to-treat analysis of the primary clinical and economic outcomes showed no evidence of a reduction in the rate of preterm birth and total costs with the screen and treat strategy compared with usual care. The rate of preterm birth was 3.8% (127 of 3333) in the screen and treat group and 4.6% (153 of 3338) in the control group (risk ratio [RR], 0.83; 95% CI, 0.66-1.05; P = .12). On average, the cost of the intervention was €203.6 (US $218.0) per participant, and the total average cost was €3344.3 (US $3580.5) in the screen and treat group vs €3272.9 (US $3504.1) in the control group, with no significant differences being observed. In the subgroup of nulliparous women (n = 3438), screen and treat was significantly more effective than usual care (RR, 0.62; 95% CI, 0.45-0.84; P for interaction = .003), whereas no statistical difference was found in multiparous (RR, 1.30; 95% CI, 0.90-1.87). Conclusion and Relevance: In this clinical trial of pregnant women at low risk of preterm birth, molecular screening and treatment for BV based on A vaginae (F vaginae) and/or G vaginalis quantification did not significantly reduce preterm birth rates. Post hoc analysis suggests a benefit of screen and treat in low-risk nulliparous women, warranting further evaluation in this group. Trial Registration: ClinicalTrials.gov Identifier: NCT02288832.

Efficacy of early intrauterine balloon tamponade for immediate postpartum hemorrhage after vaginal delivery: a randomized clinical trial.

BACKGROUND: 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. OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: 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.

Incidence and risk factors for severe postpartum haemorrhage in women with anterior low-lying or praevia placenta and prior caesarean: Prospective population-based study.

OBJECTIVE: To assess the incidence and risk factors for severe postpartum haemorrhage (PPH) in women with an anterior low-lying or praevia placenta, prior caesarean and no prenatal suspicion of placenta accreta spectrum (PAS). DESIGN: Population-based study in 176 maternity units in France. POPULATION: All women with anterior low-lying (0-19 mm from the cervical internal os) or praevia placenta, diagnosed prospectively before birth, prior caesarean and no prenatal suspicion of PAS. METHODS: Multivariable logistic regression to identify risk factors for severe PPH in the main population and after exclusion of women with PAS diagnosed only at birth. MAIN OUTCOME MEASURES: Severe PPH defined by a composite criterion either estimated blood loss of ≥1500 ml, transfusion of ≥4 or more units of packed red blood cells, embolisation or surgical treatment. RESULTS: Of the 520 114 women constituting the source population, 230 (0.44/1000 women; 95% confidence interval [CI] 0.38-0.50) met the inclusion criteria. Severe PPH rate was 24.8% (95% CI 19.2-30.4) overall, 27.5% (95% CI 21.8-33.3) in women with placenta praevia and 15.4% (95% CI 10.7-20.0) in women with low-lying placenta. PAS was diagnosed at birth in 22 women (9.9%; 95% CI 5.8-13.4), although previously unsuspected. After their exclusion, severe PPH incidence was 17.3% (95% CI 12.4-22.2). In multivariate analysis, the only factor associated with a higher severe PPH risk was placenta previa (aOR, 3.65; 95%CI, 1.20-15.8). CONCLUSION: Severe PPH is frequent among women with anterior low-lying or praevia placenta and prior caesarean, even after exclusion of women with PAS. The risk of severe PPH for those with praevia is nearly twice that with low-lying placenta.

Chorionicity and neurodevelopmental outcomes at 5½ years among twins born preterm: the EPIPAGE2 cohort study.

OBJECTIVE: To compare the neurodevelopmental outcomes of preterm twins at 5½ years by chorionicity of pregnancy. DESIGN: Prospective nationwide population-based EPIPAGE2 (Etude Epidémiologique sur les Petits Âges Gestationnels) cohort study. SETTING: A total of 546 maternity units in France, between March and December 2011. POPULATION: A total of 1126 twins eligible for follow-up at 5½ years. METHODS: The association of chorionicity with outcomes was analysed using multivariate regression models. MAIN OUTCOME MEASURES: Survival at 5½ years with or without neurodevelopmental disabilities (comprising cerebral palsy, visual, hearing, cognitive deficiency, behavioural difficulties or developmental coordination disorders) were described and compared by chorionicity. RESULTS: Among the 1126 twins eligible for follow-up at 5½ years, 926 (82.2%) could be evaluated: 228 monochorionic (MC) and 698 dichorionic (DC). Based on chronicity and gestational age of birth, we found no significant differences for severe neonatal morbidity. The rates of moderate/severe neurobehavioral disabilities were similar in infants from DC pregnancies versus infants from MC pregnancies (OR 1.22, 95% CI 0.65-2.28). By gestational age and without twin-twin transfusion syndrome (TTTS), no difference according to chorionicity was found for all neurodevelopmental outcome measures. CONCLUSIONS: The neurodevelopmental outcomes among preterm twins at 5½ years is similar, irrespective of chorionicity.

Second-trimester amniotic fluid proteins changes in subsequent spontaneous preterm birth.

INTRODUCTION: The global sequence of the pathogenesis of preterm labor remains unclear. This study aimed to compare amniotic fluid concentrations of extracellular matrix-related proteins (procollagen, osteopontin and IL-33), and of cytokines (IL-19, IL-6, IL-20, TNFα, TGFß, and IL-1ß) in asymptomatic women with and without subsequent spontaneous preterm delivery. MATERIAL AND METHODS: We used amniotic fluid samples of singleton pregnancy, collected by amniocentesis between 16 and 20 weeks' gestation, without stigmata of infection (i.e., all amniotic fluid samples were tested with broad-range 16 S rDNA PCR to distinguish samples with evidence of past bacterial infection from sterile ones), during a randomized, double-blind, placebo-controlled trial to perform a nested case-control laboratory study. Cases were women with a spontaneous delivery before 37 weeks of gestation (preterm group). Controls were women who gave birth at or after 39 weeks (full term group). Amniotic fluid concentrations of the extracellular matrix-related proteins and cytokines measured by immunoassays were compared for two study groups. CLINICALTRIALS: gov: NCT00718705. RESULTS: Between July 2008 and July 2011, in 12 maternal-fetal medicine centers in France, 166 women with available PCR-negative amniotic fluid samples were retained for the analysis. Concentrations of procollagen, osteopontin, IL-19, IL-6, IL-20, IL-33, TNFα, TGFß, and IL-1ß were compared between the 37 who gave birth preterm and the 129 women with full-term delivery. Amniotic fluid levels of procollagen, osteopontin, IL-19, IL-33, and TNFα were significantly higher in the preterm than the full-term group. IL-6, IL-20, TGFß, and IL-1ß levels did not differ between the groups. CONCLUSIONS: In amniotic fluid 16 S rDNA PCR negative samples obtained during second-trimester amniocentesis, extracellular matrix-related protein concentrations (procollagen, osteopontin and IL-33), together with IL-19 and TNFα, were observed higher at this time in cases of later spontaneous preterm birth.

Glycemia and Neonatal Encephalopathy: Outcomes in the LyTONEPAL (Long-Term Outcome of Neonatal Hypoxic EncePhALopathy in the Era of Neuroprotective Treatment With Hypothermia) Cohort.

OBJECTIVES: To assess in newborns with neonatal encephalopathy (NE), presumptively related to a peripartum hypoxic-ischemic event, the frequency of dysglycemia and its association with neonatal adverse outcomes. STUDY DESIGN: We conducted a secondary analysis of LyTONEPAL (Long-Term Outcome of Neonatal hypoxic EncePhALopathy in the era of neuroprotective treatment with hypothermia), a population-based cohort study including 545 patients with moderate-to-severe NE. Newborns were categorized by the glycemia values assessed by routine clinical care during the first 3 days of life: normoglycemic (all glycemia measurements ranged from 2.2 to 8.3 mmol/L), hyperglycemic (at least 1 measurement >8.3 mmol/L), hypoglycemic (at least 1 measurement <2.2 mmol/L), or with glycemic lability (measurements included at least 1 episode of hypoglycemia and 1 episode of hyperglycemia). The primary adverse outcome was a composite outcome defined by death and/or brain lesions on magnetic resonance imaging, regardless of severity or location. RESULTS: In total, 199 newborns were categorized as normoglycemic (36.5%), 74 hypoglycemic (13.6%), 213 hyperglycemic (39.1%), and 59 (10.8%) with glycemic lability, based on the 2593 glycemia measurements collected. The primary adverse outcome was observed in 77 (45.8%) normoglycemic newborns, 37 (59.7%) with hypoglycemia, 137 (67.5%) with hyperglycemia, and 40 (70.2%) with glycemic lability (P < .01). With the normoglycemic group as the reference, the aORs and 95% 95% CIs for the adverse outcome were significantly greater for the group with hyperglycemia (aOR 1.81; 95% CI 1.06-3.11). CONCLUSIONS: Dysglycemia affects nearly two-thirds of newborns with NE and is independently associated with a greater risk of mortality and/or brain lesions on magnetic resonance imaging. TRIAL REGISTRATION: NCT02676063.