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.

Growth charts for use at birth and in the neonatal period: Recommendations of the French Neonatal Society.

INTRODUCTION: The use of different growth charts can lead to confusion in discussions between professionals. There are obstetric charts (of fetal growth) and neonatal charts (of measurements at birth and of postnatal growth). These charts can be descriptive (derived from an unselected population) or prescriptive (derived from of a population at low risk and with optimal conditions for growth). OBJECTIVES: (1) To describe available charts for infants at birth and in the neonatal period and compare them, and (2) to recommend one or more charts for use in neonatology in France. METHODS: Bibliographic research was conducted on MEDLINE and completed by the guidelines of professional societies. RESULTS: Antenatal information about fetal growth restriction or fetuses identified as small-for-gestational-age using Intrauterine charts must be integrated into the identification of newborns at risk, but the use of Intrauterine charts to evaluate birthweight is not recommended to allow consistency with postnatal charts used in neonatal practice. Z-score variations using the updated Fenton postnatal charts are the most appropriate for the assessment of birthweight and postnatal growth for infants born preterm. These charts are sex-specific, include the three measurements (length, weight, and head circumference) and enable longitudinal follow-up of growth up to 50 weeks of corrected age and are linked to the World Health Organization charts at term. The French Audipog charts, although are individualized, accessible online and can be used in maternity units to evaluate birthweight for term infants, but do not allow the follow-up of postnatal growth, while Fenton charts may be used to evaluate birthweight and postnatal growth in the first month for hospitalized term infants. CONCLUSION: The updated Fenton charts are the neonatal charts that best suit the objectives of pediatricians in France for monitoring the growth of preterm newborns. The use of the Audipog charts at term remains an alternative in maternity wards, while Fenton charts can be used for hospitalized term newborns.

Anti-RH1 alloimmunization: At what maternal antibody threshold is there a risk of severe fetal anemia?

BACKGROUND: To define a threshold of maternal antibodies at risk of severe fetal anemia in patients followed for anti-RH1 alloimmunization (AI). STUDY, DESIGN, AND METHODS: We conducted a retrospective study of patients followed for anti-RH1 AI at the Lille University Hospital. The first group, severe anemia, included patients who received one or more in utero transfusions (IUT) or who were induced before 37 weeks of pregnancy for suspected severe fetal anemia. The second group, absence of severe anemia, corresponded to patients without intervention during pregnancy related to AI. Sensitivities, specificities, and positive and negative predictive values for screening for severe fetal anemia were calculated for the antibody thresholds of 3.5 and 5 IU/ml for the quantification. RESULTS: Between 2000 and 2018, 207 patients were included 135 in the severe anemia group and 72 in the no severe anemia group. No severe anemia was observed for an antibody titer below 16. For an antibody threshold of 3.5 IU/ml, the sensitivity was 98.2%, with 30.2% false positives. All severe anemias were detected in the second trimester; two cases of severe anemia were not detected in the third trimester. For an antibody threshold of 5 IU/ml, the sensitivity was lower at 95.6%, with five cases of severe anemia not detected. CONCLUSION: The antibody threshold of 3.5 IU/ml for the quantification and 16 for the titration allow targeting patients requiring close monitoring by an experienced team in case of anti-RH1 AI.

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.

Factors associated with a maternal lower-limb neurological deficit after vaginal delivery.

INTRODUCTION: The etiology of lower-limb neurological deficit after vaginal delivery remains poorly understood. The objective herein was to identify factors associated with this maternal nerve injury after vaginal delivery. MATERIAL AND METHODS: A single-center, case-control (matching 1:4) study. Cases were women with a lower-limb neurological deficit that appeared immediately after vaginal delivery. Controls were randomly selected women who gave birth vaginally during the same period, without any deficit. Finally, to assess the rates of factors associated with these deficits, we studied them using a randomly selected 5% sample of the population with vaginal deliveries. RESULTS: During the 30-month study period, 31 cases were identified among 10 333 women who gave birth vaginally (0.3%, 95% CI 0.20-0.43); 124 controls were also included. After logistic regression, the presence of a neurological deficit after delivery was associated with second-stage labor duration (per hour odds ratio [OR] 3.67, 95% CI 2.09-6.44; OR per standard deviation increase 2.73, 95% CI 1.75-4.25, p < 0.001) and instrumental delivery (OR = 3.24, 95% CI 1.29-8.14, p = 0.012), with no interaction effect (p = 0.56). Extrapolation of these factors to a 5% sample of the overall population of women with vaginal births showed that the rate of these deficits would be very low for women with second-stage labor lasting up to 90 min without instrumental delivery (0.05%) but increased to 1.52% when these factors were combined (OR 33.1, 95% CI 9.4-116.9). CONCLUSIONS: Following vaginal delivery, the onset of a neurological deficit is principally associated with the duration of second-stage labor and instrumental delivery.

Risk factors associated with shortened latency before delivery in outpatients managed for preterm prelabor rupture of membranes.

INTRODUCTION: Preterm prelabor rupture of membranes (PPROM) occurs in 3% of pregnancies and is the main cause (~30%) of premature delivery. Home care seems to be a safe alternative for the management of patients with PPROM, who have a longer latency than those with PPROM managed with conventional hospitalization. We aimed to identify the risk factors associated with a shortened latency before delivery in women with PPROM managed as outpatients. MATERIAL AND METHODS: The design was a retrospective cohort study and the setting was a Monocentric Tertiary centre (Lille University Hospital, France) from 2009 to 2018. All consecutive patients in home care after PPROM at 24-36 weeks were included. For the main outcome measure we calculated the latency ratio for each patient as the ratio of the real latency period to the expected latency period, expressed as a percentage. The risk factors influencing this latency ratio were evaluated. RESULTS: A total of 234 patients were managed at home after PPROM. Mean latency was 35.5 ± 20.7 days, corresponding to an 80% latency ratio. In 196 (83.8%) patients the length of home care was more than 7 days. A lower latency ratio was significantly associated with oligohydramnios (p < 0.001), gestational age at PPROM (p = 0.006), leukocyte count at PPROM more than 12 × 109 /L (p = 0.025), and C-reactive protein concentration more than 5 mg/L at 7 days after PPROM (p = 0.046). Cervical length was not associated with a lower latency ratio. CONCLUSIONS: Women with PPROM managed with home care are stable. The main risk factor associated with a reduced latency is oligohydramnios. Outpatients with oligohydramnios should be informed of the probability of a shortened latency period.

Types of intrapartum hypoxia in the newborn at term with metabolic acidemia: A retrospective study.

INTRODUCTION: In the most recent recommendations of the International Federation of Gynecology and Obstetrics (FIGO), a chapter was dedicated to the physiological approach and to the description of fetal mechanisms developed to respond to hypoxia. Our objective was to classify the type of hypoxia in the case of metabolic acidemia and to describe the order of appearance of fetal heart rate abnormalities in cases of gradually evolving hypoxia. MATERIAL AND METHODS: 132 neonates born between 2018 and 2020 with acidemia were included. We excluded preterm birth, fetuses with congenital anomaly and twin pregnancies. Intrapartum cardiotocography traces were assigned to one of these four types of labor hypoxia: acute, subacute, gradually evolving and chronic hypoxia. For gradually evolving hypoxia, fetal heart rate abnormalities were described according to the FIGO classification. RESULTS: 36 cardiotocography traces (27.3%) were classified as acute hypoxia, 14 (10.6%) as subacute hypoxia, and 3 (3.2%) as chronic hypoxia; gradually evolving hypoxia occurred in 62 cases (47%). In 77.4% of cases of gradually evolving hypoxia, deceleration was the first anomaly to appear, with loss of variability and bradycardia appearing later. Increased fetal heart rate was observed immediately after late deceleration in 46.8% of cases and was followed by a loss of variability or saltatory rhythm in 37.1% of cases. CONCLUSIONS: In cases of metabolic acidemia at term, the most frequent situation observed was gradually evolving hypoxia, with an initial occurrence of decelerations. The sequence of fetal heart rate modifications was variable.

Should pregnant women with anticoagulant prophylaxis benefit from scheduled delivery?

PURPOSE: When vaginal delivery is considered in women with low-molecular-weight heparin (LMWH) treatment, epidural analgesia is contraindicated for 12-24 h after the last injection. We evaluated the proportion of epidural analgesia depending on whether this is scheduled delivery (labor induction after stopping LMWH) or unscheduled delivery (stopping LMWH at labor onset). METHODS: Retrospective hospital study running from 2015 to 2017. Inclusion criteria for patients with LMWH treatment were: singleton pregnancy, gestational age ≥ 38 weeks of gestation and possible vaginal delivery. The primary endpoint was the epidural analgesia rate. Secondary endpoints included risks for caesarean section, deep vein thrombosis, and postpartum hemorrhage. RESULTS: Among 129 patients, 54 had scheduled delivery (41.9%). In practice, only 44 of them had labor induction (81.5%) and 54 of the 75 patients in the unscheduled delivery group had spontaneous delivery (72.0%). There was no significant difference in the rate of epidural analgesia between the "scheduled" and "unscheduled" groups (52/54 (96.3%) vs. 66/75 (88.0%) (p = 0.12)), and no difference in the secondary endpoints. CONCLUSION: High access rates to epidural analgesia are observed in both scheduled and unscheduled deliveries. Scheduled delivery does not appear to be a really advantageous strategy for women with LMWH prophylaxis.

Association of Chorioamnionitis with Cerebral Palsy at Two Years after Spontaneous Very Preterm Birth: The EPIPAGE-2 Cohort Study.

OBJECTIVE: To assess whether chorioamnionitis is associated with cerebral palsy (CP) or death at 2 years' corrected age in infants born before 32 weeks of gestation after spontaneous birth. STUDY DESIGN: EPIPAGE-2 is a national, prospective, population-based cohort study of children born preterm in France in 2011; recruitment periods varied by gestational age. This analysis includes infants born alive after preterm labor or preterm premature rupture of membranes from 240/7 to 316/7 weeks of gestation. We compared the outcomes of CP, death at 2 years' corrected age, and "CP or death at age 2" according to the presence of either clinical chorioamnionitis or histologic chorioamnionitis. All percentages were weighted by the duration of the recruitment period. RESULTS: Among 2252 infants born alive spontaneously before 32 weeks of gestation, 116 (5.2%) were exposed to clinical chorioamnionitis. Among 1470 with placental examination data available, 639 (43.5%) had histologic chorioamnionitis. In total, 346 infants died before 2 years and 1586 (83.2% of the survivors) were evaluated for CP at age 2 years. CP rates were 11.1% with and 5.0% without clinical chorioamnionitis (P = .03) and 6.1% with and 5.3% without histologic chorioamnionitis (P = .49). After adjustment for confounding factors, CP risk rose with clinical chorioamnionitis (aOR 2.13, 95% CI 1.12-4.05) but not histologic chorioamnionitis (aOR 1.21, 95% 0.75-1.93). Neither form was associated with the composite outcome "CP or death at age 2." CONCLUSIONS: Among infants very preterm born spontaneously, the risk of CP at a corrected age of 2 years was associated with exposure to clinical chorioamnionitis but not histologic chorioamnionitis.

Risk factors for failed induction of labor among pregnant women with Class III obesity.

INTRODUCTION: Our aim was to identify risk factors for failed induction in morbidly obese patients undergoing the induction of labor at term. MATERIAL AND METHODS: This was a retrospective multicenter study on a cohort of 235 patients with a body mass index greater than 40 kg/m2 and giving birth to a singleton in cephalic presentation, who had an induction of labor from 38 weeks of amenorrhea. Scheduled cesareans and spontaneous vaginal deliveries were excluded. Maternal, peri-partum and neonatal characteristics were analyzed according to the delivery route. RESULTS: In all, 235 patients were included. Of these, 62.5% patients delivered vaginally and 37.5% by cesarean section. The frequency of nulliparity was greater in patients who had a cesarean section (56 [interquartile range, IQR, 38.1] vs 56 [IQR 63.6], P < .001). In multivariate analysis, nulliparity (odds ratio [OR] 2.81, 95% confidence interval [CI] 1.58-4.97], P < .001), low Bishop's score (OR .794, 95% CI .70-.90, P < .001) and weight gain (OR 1.04, 95% CI 1.01-1.08, P = .033) were independent risk factors for failed induction. Umbilical cord pH at birth lower than 7 (0 vs 7 [IQR 8.0], P < .001) and lower than 7.20 (36 [IQR 24.5] vs 35 [IQR 39.8], P = .014) as well as the Apgar at 1 minute (14 [IQR 9.5] vs 17 [IQR 19.3], P = .032) was significantly higher in infants born by cesarean section. CONCLUSIONS: In this cohort, 63% of women with Class III obesity had successful inductions of labor; risk factors for failed induction include nulliparity and unfavorable Bishop score.

Planned delivery route and outcomes of cephalic singletons born spontaneously at 24-31 weeks' gestation: The EPIPAGE-2 cohort study.

INTRODUCTION: The objective of this study was to investigate the association between planned mode of delivery and neonatal outcomes with spontaneous very preterm birth among singletons in cephalic presentation. MATERIAL AND METHODS: Etude Epidémiologique sur les Petits Ages Gestationnels 2 is a French national, prospective, population-based cohort study of preterm infants. For this study, we included women with a singleton cephalic pregnancy and spontaneous preterm labor or preterm premature rupture of membranes at 24-31 weeks' gestation. The main exposure was the planned mode of delivery (ie planned vaginal delivery or planned cesarean delivery at the initiation of labor). The primary outcome was survival at discharge and secondary outcome survival at discharge without severe morbidity. Propensity scores were used to minimize indication bias in estimating the association. RESULTS: The study population consisted of 1008 women: 206 (20.4%) had planned cesarean delivery and 802 (79.6%) planned vaginal delivery. In all, 723 (90.2%) finally had a vaginal delivery. Overall, 187 (92.0%) and 681 (87.0%) neonates in the planned cesarean delivery and planned vaginal delivery groups were discharged alive, and 156 (77.6%) and 590 (76.3%) were discharged alive without severe morbidity. After matching on propensity score, planned cesarean delivery was not associated with survival (adjusted odds ratio [aOR] 1.05, 95% confidence interval [CI] 0.48-2.28) or survival without severe morbidity (aOR 0.64, 95% CI 0.36-1.16). CONCLUSIONS: Planned cesarean delivery for cephalic presentation at 24-31 weeks' gestation after preterm labor or preterm premature rupture of membranes does not improve neonatal outcomes.

Early clindamycin for bacterial vaginosis in pregnancy (PREMEVA): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Preterm delivery during pregnancy (<37 weeks' gestation) is a leading cause of perinatal mortality and morbidity. Treating bacterial vaginosis during pregnancy can reduce poor outcomes, such as preterm birth. We aimed to investigate whether treatment of bacterial vaginosis decreases late miscarriages or spontaneous very preterm birth. METHODS: PREMEVA was a double-blind randomised controlled trial done in 40 French centres. Women aged 18 years or older with bacterial vaginosis and low-risk pregnancy were eligible for inclusion and were randomly assigned (2:1) to three parallel groups: single-course or triple-course 300 mg clindamycin twice-daily for 4 days, or placebo. Women with high-risk pregnancy outcomes were eligible for inclusion in a high-risk subtrial and were randomly assigned (1:1) to either single-course or triple-course clindamycin. The primary outcome was a composite of late miscarriage (16-21 weeks) or spontaneous very preterm birth (22-32 weeks), which we assessed in all patients with delivery data (modified intention to treat). Adverse events were systematically reported. This study is registered with ClinicalTrials.gov, number NCT00642980. FINDINGS: Between April 1, 2006, and June 30, 2011, we screened 84 530 pregnant women before 14 weeks' gestation. 5630 had bacterial vaginosis, of whom 3105 were randomly assigned to groups in the low-risk trial (n=943 to receive single-course clindamycin, n=968 to receive triple-course clindamycin, and n=958 to receive placebo) or high-risk subtrial (n=122 to receive single-course clindamycin and n=114 to receive triple-course clindamycin). In 2869 low-risk pregnancies, the primary outcome occurred in 22 (1·2%) of 1904 participants receiving clindamycin and 10 (1·0%) of 956 participants receiving placebo (relative risk [RR] 1·10, 95% CI 0·53-2·32; p=0·82). In 236 high-risk pregnancies, the primary outcome occurred in 5 (4·4%) participants in the triple-course clindamycin group and 8 (6·0%) participants in the single-course clindamycin group (RR 0·67, 95% CI 0·23-2·00; p=0·47). In the low-risk trial, adverse events were more common in the clindamycin groups than in the placebo group (58 [3·0%] of 1904 vs 12 [1·3%] of 956; p=0·0035). The most commonly reported adverse event was diarrhoea (30 [1·6%] in the clindamycin groups vs 4 [0·4%] in the placebo group; p=0·0071); abdominal pain was also observed in the clindamycin groups (9 [0·6%] participants) versus none in the placebo group (p=0·034). No severe adverse event was reported in any group. Adverse fetal and neonatal outcomes did not differ significantly between groups in the high-risk subtrial. INTERPRETATION: Systematic screening and subsequent treatment for bacterial vaginosis in women with low-risk pregnancies shows no evidence of risk reduction of late miscarriage or spontaneous very preterm birth. Use of antibiotics to prevent preterm delivery in this patient population should be reconsidered. FUNDING: French Ministry of Health.

Determinants of influenza vaccination uptake in pregnancy: a large single-Centre cohort study.

BACKGROUND: Although vaccination of pregnant women against influenza is recommended, the vaccination rate remains low. We conducted a study to identify determinants of influenza vaccination uptake in pregnancy in order to identify strategies to improve seasonal influenza vaccination rates. METHODS: Prospective observational hospital-based study in the French hospital performing the highest number of deliveries, located in the city of Lille, among all women who had given birth during the 2014-2015 influenza season. Data were collected through a self-completed questionnaire and from medical files. The vaccination uptake was self-reported. Determinants of vaccination uptake were identified using logistic regression analysis. RESULTS: Of the 2045 women included in the study, 35.5% reported that they had been vaccinated against influenza during their pregnancy. The principal factors significantly associated with greater vaccination uptake were previous influenza vaccination (50.9% vs 20.2%, OR 4.1, 95% CI 3.1-5.5), nulliparity (41.0% vs 31.3%, OR 2.5, 95% CI 1.7-3.7), history of preterm delivery < 34 weeks (43.4% vs 30.3%, OR 2.3, 95% CI 1.1-4.9), the mother's perception that the frequency of vaccine complications for babies is very low (54.6% vs 20.6%, OR 1.1, 95% CI 0.5-2.2), the mother's good knowledge of influenza and its vaccine (61.7% vs 24.4%, OR 3.1, 95% CI 2.2-4.4), hospital-based prenatal care in their first trimester of pregnancy (55.0% vs 30.2%, OR 2.1, 95% CI 1.2-3.7), vaccination recommendations during pregnancy by a healthcare worker (47.0% vs 2.7%, OR 18.8, 95% CI 10.0-35.8), receipt of a vaccine reimbursement form (52.4% vs 18.6%, OR 2.0, 95% CI 1.5-2.7), and information from at least one healthcare worker about the vaccine (43.8% vs 19.1%, OR 1.8, 95% CI 1.3-2.6). CONCLUSIONS: Our findings suggest that in order to increase flu vaccination compliance among pregnant women, future public health programmes must ensure cost-free access to vaccination, and incorporate education about the risks of influenza and the efficacy/safety of vaccination and clear recommendations from healthcare professionals into routine antenatal care.

Maternal red blood cell alloimmunization requiring intrauterine transfusion: a comparative study on management and outcome depending on the type of antibody.

BACKGROUND: The antibody primarily responsible for fetal anemia may influence treatment and prognosis. The primary objective was to compare ante- and postnatal management and the outcomes of maternal red blood cell (RBC) alloimmunizations according to the antibody involved. The secondary objective was to compare anti-D alloimmunizations according to associated number of antibodies. STUDY DESIGN AND METHODS: A single-center study from 1999 to 2015 including maternal RBC alloimmunizations requiring intrauterine transfusion (IUT) was conducted. Patients were classified according to the antibody involved: anti-D, other Rh (anti-c and anti-E), and anti-K1. Obstetric data, IUT characteristics, and neonatal outcome were compared. A specific study on the anti-D, when isolated or associated, was then conducted. RESULTS: There were 106 pregnancies included, with 77.4% having anti-D, 9.4% having another anti-Rh (Rh group), and 13.2% having anti-K1. No significant difference between the anti-D and Rh groups was found for management and prognosis. The hemoglobin level in the first IUT was higher in the anti-D group than in the Kell group (6.8 vs. 4.7 g/dL, p = 0.008). Newborns in the anti-D group had significantly higher bilirubin levels and phototherapy duration than those in the Kell group. The mean estimated daily decrease in hemoglobin and that between the first two IUTs were lower with an isolated anti-D, compared with anti-D associated with two antibodies (p = 0.04). CONCLUSION: Anti-K1 alloimmunizations seem to cause more severe fetal anemia than anti-D alloimmunizations. Moreover, a decrease in hemoglobin appears to be more rapid when anti-D is associated with other antibodies.

Preterm premature rupture of membranes at 22-25 weeks' gestation: perinatal and 2-year outcomes within a national population-based study (EPIPAGE-2).

BACKGROUND: Most clinical guidelines state that with early preterm premature rupture of membranes, obstetric and pediatric teams must share a realistic and individualized appraisal of neonatal outcomes with parents and consider their wishes for all decisions. However, we currently lack reliable and relevant data, according to gestational age at rupture of membranes, to adequately counsel parents during pregnancy and to reflect on our policies of care at these extreme gestational ages. OBJECTIVE: We sought to describe both perinatal and 2-year outcomes of preterm infants born after preterm premature rupture of membranes at 22-25 weeks' gestation. STUDY DESIGN: EPIPAGE-2 is a French national prospective population-based cohort of preterm infants born in 546 maternity units in 2011. Inclusion criteria in this analysis were women diagnosed with preterm premature rupture of membranes at 22-25 weeks' gestation and singleton or twin gestations with fetus(es) alive at rupture of membranes. Latency duration, antenatal management, and outcomes (survival at discharge, survival at discharge without severe morbidity, and survival at 2 years' corrected age without cerebral palsy) were described and compared by gestational age at preterm premature rupture of membranes. RESULTS: Among the 1435 women with a diagnosis of preterm premature rupture of membranes, 379 were at 22-25 weeks' gestation, with 427 fetuses (331 singletons and 96 twins). Median gestational age at preterm premature rupture of membranes and at birth were 24 (interquartile range 23-25) and 25 (24-27) weeks, respectively. For each gestational age at preterm premature rupture of membranes, nearly half of the fetuses were born within the week after the rupture of membranes. Among the 427 fetuses, 51.7% were survivors at discharge (14.1%, 39.5%, 66.8%, and 75.8% with preterm premature rupture of membranes at 22, 23, 24, and 25 weeks, respectively), 38.8% were survivors at discharge without severe morbidity, and 46.4% were survivors at 2 years without cerebral palsy, with wide variations by gestational age at preterm premature rupture of membranes. Survival at 2 years without cerebral palsy was low with preterm premature rupture of membranes at 22 and 23 weeks but reached approximately 60% and 70% with preterm premature rupture of membranes at 24 and 25 weeks. CONCLUSION: Preterm premature rupture of membranes at 22-25 weeks is associated with high incidence of mortality and morbidity, with wide variations by gestational age at preterm premature rupture of membranes. However, a nonnegligible proportion of children survive without severe morbidity both at discharge and at 2 years' corrected age.

Preterm premature rupture of membranes: Which criteria contraindicate home care management?

INTRODUCTION: Home care management offers a suitable alternative to hospitalization for management of preterm premature rupture of membranes (PPROM). Eligibility criteria have not been clearly established. Our aim was to determine predictive factors of complication during home care management of PPROM in order to define optimal eligibility criteria. MATERIAL AND METHODS: Retrospective cohort study of all women with singleton pregnancies with PPROM managed as outpatients between 2009 and 2015. Complications were defined as the occurrence of one of these events: fetal death, placental abruption, umbilical cord prolapse, delivery outside maternity hospital, neonatal death. RESULTS: In all, 187 women with PPROMs were managed as outpatients, of whom 12 had a complication (6.4%). In the "complication" group, gestational age at diagnosis (P = 0.006) and at delivery (P < 0.001) were lower, with no difference in latency between these two events. Three criteria significantly increased the risk for a severe complication: PPROM occurring before 26 weeks (P = 0.008), non-cephalic fetal presentation (P = 0.02) and oligoamnios (P = 0.02). When unfavorable criteria were associated with PPROM, the risk was increased (1 criterion, odds ratio [OR] 1.6; 2 criteria, OR 6.9 and 3 criteria, OR 32.8). CONCLUSIONS: Combination of these three criteria is an indication for conventional hospitalization to limit maternal and fetal morbidity. When two criteria are combined, home care should be discussed for each case. If only one unfavorable criteria is present, outpatient management is suitable. To validate these results, a prospective randomized study should be conducted.

Histologic Chorioamnionitis and Bronchopulmonary Dysplasia in Preterm Infants: The Epidemiologic Study on Low Gestational Ages 2 Cohort.

OBJECTIVE: To investigate the association between histologic chorioamnionitis (HCA) and bronchopulmonary dysplasia (BPD) in very preterm infants, both in a general population and for those born after spontaneous preterm labor and after preterm premature rupture of membranes (pPROM). STUDY DESIGN: This study included 2513 live born singletons delivered at 24-31 weeks of gestation from a national prospective population-based cohort of preterm births; 1731 placenta reports were available. HCA was defined as neutrophil infiltrates in the amnion, chorion of the membranes, or chorionic plate, associated or not with funisitis. The main outcome measure was moderate or severe BPD. Analyses involved logistic regressions and multiple imputation for missing data. RESULTS: The incidence of HCA was 28.4% overall: 38% in cases of preterm labor, 64% in cases of pPROM, and less than 5% in cases of vascular disorders. Overall, the risk of BPD after adjustment for gestational age, sex, and antenatal steroids was reduced for infants with HCA (HCA alone: aOR 0.6 [95% CI 0.4-0.9]; associated with funisitis: aOR 0.5 [95% CI 0.3-0.8]). This finding was explained by the high rate of BPD and low rate of chorioamnionitis among children with fetal growth restriction. HCA was not associated with BPD in the preterm labor (13.4% vs 8.5%; aOR 0.9; 95% CI 0.5-1.8) or in the pPROM group (12.9% vs 12.1%; aOR 0.6; 95% CI 0.3-1.3). CONCLUSION: In homogeneous groups of infants born after preterm labor or pPROM, HCA is not associated with BPD.

Impact of Latency Duration on the Prognosis of Preterm Infants after Preterm Premature Rupture of Membranes at 24 to 32 Weeks' Gestation: A National Population-Based Cohort Study.

OBJECTIVE: To assess the impact of latency duration on survival, survival without severe morbidity, and early-onset sepsis in infants born after preterm premature rupture of membranes (PPROM) at 24-32 weeks' gestation. STUDY DESIGN: This study was based on the prospective national population-based Etude Épidémiologique sur les Petits Ȃges Gestationnels 2 cohort of preterm births and included 702 singletons delivered in France after PPROM at 24-32 weeks' gestation. Latency duration was defined as the time from spontaneous rupture of membranes to delivery, divided into 4 periods (12 hours to 2 days [reference], 3-7 days, 8-14 days, and >14 days). Multivariable logistic regression was used to assess the relationship between latency duration and survival, survival without severe morbidity at discharge, or early-onset sepsis. RESULTS: Latency duration ranged from 12 hours to 2 days (18%), 3-7 days (38%), 8-14 days (24%), and >14 days (20%). Rates of survival, survival without severe morbidity, and early-onset sepsis were 93.5% (95% CI 91.8-94.8), 85.4% (82.4-87.9), and 3.4% (2.0-5.7), respectively. A crude association found between prolonged latency duration and improved survival disappeared on adjusting for gestational age at birth (aOR 1.0 [reference], 1.6 [95% CI 0.8-3.2], 1.2 [0.5-2.9], and 1.0 [0.3-3.2] for latency durations from 12 hours to 2 days, 3-7 days, 8-14 days, and >14 days, respectively). Prolonged latency duration was not associated with survival without severe morbidity or early-onset sepsis. CONCLUSION: For a given gestational age at birth, prolonged latency duration after PPROM does not worsen neonatal prognosis.

Should optimal timing between two intrauterine transfusions be based on estimated daily decrease of hemoglobin or on measurement of fetal middle cerebral artery peak systolic velocity?

BACKGROUND: To best predict the recurrence of fetal anemia after intrauterine transfusion (IUT), the measurement of middle cerebral artery peak systolic velocity (PSV) and the estimation of hemoglobin (Hb) daily decrease are compared. STUDY DESIGN AND METHODS: A retrospective study including 38 patients who had at least two IUTs in a context of red blood cell alloimmunization was conducted. PSV values before first, second, and third IUTs were collected and expected Hb level was calculated according to various Hb daily decrease formulas as proposed in the literature. RESULTS: Comparison of PSV receiver operating characteristic curves with the various Hb levels did not find any significant difference between first and second IUTs. On the other hand, we found a significant difference between the second and third IUTs, with better prediction of fetal anemia through Hb decrease calculation, whatever the formula. Between the second and third IUTs, no formula was significantly better than the others. CONCLUSION: The timing of a second transfusion can be difficult to determine with certainty, but PSV can give an accurate assessment of when to resample the fetus with probably a higher recommended threshold for the diagnosis of fetal anemia. Subsequent to a second transfusion, the intertransfusion interval should be based on estimated Hb decrease rather than PSV thresholds, whatever the chosen formula proposed in the literature. Larger numbers are needed to definitely make this recommendation and it will be interesting to evaluate correlation between different antibodies.

Perinatal outcome of placental massive perivillous fibrin deposition: a case-control study.

OBJECTIVE: The objectives of the study are to describe the obstetric outcomes associated with massive perivillous fibrin deposition (MFD) compared with a control series and to determine if outcome differs according to the extent of fibrin deposition. METHOD: Retrospective case-control study based on placentas analyzed over a consecutive 12-year period. MFD was considered severe if it extended over more than 50% of the placenta and moderate between 25% and 50%. RESULTS: During the study period, MFD was observed on 71 placentas, 39 severe and 32 moderate. Compared with the 142 control women, the 39 women with severe MFD more often had histories of autoimmune disease and intrauterine fetal death. The case women with MFD were associated with elevated levels of maternal alpha-fetoprotein and with a high risk of severe growth restriction and/or intrauterine death. Compared with the infants with moderate MFD, those with severe MFD had also more abnormal umbilical artery Doppler velocimetry findings and more often intrauterine deaths and lower birthweights. CONCLUSION: Regardless of their extent, MFD that covered at least 25% of the placenta was almost always accompanied by severe growth restriction and by a high risk of intrauterine fetal death. Moreover, severe MFD tend to be associated with autoimmune diseases of the mothers, and pregnancies show more often a pathologic Doppler of the umbilical arteries and more often intrauterine fetal death that the moderate form. © 2017 John Wiley & Sons, Ltd.