Accuracy of the combination of commercially available biomarkers and cervical length measurement to predict preterm birth in symptomatic women: A systematic review.

An accurate prognostic method for preterm birth (PTB) could avoid unnecessary treatment(s) with potentially negative effects. The objective was to explore the prognostic accuracy of commercially available bedside cervicovaginal biomarker tests in combination with cervical length (CL) compared to CL measurement alone and/or a biomarker test alone, for PTB within 7 days after testing symptomatic women at 22-34 weeks. The MEDLINE, Cochrane, Embase and Web of Science databases were searched from inception to August 28th, 2019. Seven hundred and eight articles were identified and screened using Rayyan. Studies reporting on the predictive accuracy of combined tests compared to CL or biomarker alone for the prediction of PTB within 7 days of testing in symptomatic women with intact membranes were included. A piloted data extraction form was used. Direct comparisons of the prognostic accuracy of the combination test with CL measurement or a biomarker alone were done, as well as comparisons of prognostic accuracy of the included combination tests (indirect comparisons). Twelve articles were included (seven on fetal fibronectin, four on phosphorylated insulin-like growth factor binding protein-1, one comparing both). A variety of CL cut-offs was reported. The results could not demonstrate superiority of a combination method compared to single methods. Due to data scarcity and quality, the superiority of either predictive test for PTB, either combination or single, cannot be demonstrated with this systematic review. We recommend further research to compare available biomarkers.

Association between extremely preterm caesarean delivery and maternal depressive and anxious symptoms: a national population-based cohort study.

OBJECTIVE: To evaluate whether caesarean delivery before 26 weeks of gestation was associated with symptoms of depression and anxiety in mothers in comparison with deliveries between 26 and 34 weeks. DESIGN: Prospective national population-based EPIPAGE-2 cohort study. SETTING: 268 neonatology departments in France, March to December 2011. POPULATION: Mothers who delivered between 22 and 34 weeks and whose self-reported symptoms of depression (Center for Epidemiologic Studies Depression Scale: CES-D) and anxiety (State-Trait Anxiety Inventory: STAI) were assessed at the moment of neonatal discharge. METHODS: The association of caesarean delivery before 26 weeks with severe symptoms of depression (CES-D ≥16) and anxiety (STAI ≥45) was assessed by weighted and design-based log-linear regression model. MAIN OUTCOME MEASURES: Severe symptoms of depression and anxiety in mothers of preterm infants. RESULTS: Among the 2270 women completing CES-D and STAI questionnaires at the time of neonatal discharge, severe symptoms of depression occurred in 25 (65.8%) women having a caesarean before 26 weeks versus in 748 (50.6%) women having a caesarean after 26 weeks. Caesarean delivery before 26 weeks was associated with severe symptoms of depression compared with caesarean delivery after 26 weeks (adjusted relative risk [aRR] 1.42, 95% CI 1.12-1.81) adjusted to neonatal birthweight and severe neonatal morbidity among other factors. There was no evidence of an association between mode of delivery and symptoms of anxiety. CONCLUSIONS: Mothers having a caesarean delivery before 26 weeks' gestation are at high risk of symptoms of depression and may benefit from specific preventive care. TWEETABLE ABSTRACT: Mothers having caesarean delivery before 26 weeks' gestation are at high risk of symptoms of depression.

The impact of chorionicity on pregnancy outcome and neurodevelopment at 2 years old among twins born preterm: the EPIPAGE-2 cohort study.

OBJECTIVE: To compare the short- and mid-term outcomes of preterm twins by chorionicity of pregnancy. DESIGN: Prospective nationwide population-based EPIPAGE-2 cohort study. SETTING: 546 maternity units in France, between March and December 2011. POPULATION: A total of 1700 twin neonates born between 24 and 34 weeks of gestation. METHODS: The association of chorionicity with outcomes was analysed using multivariate regression models. MAIN OUTCOME MEASURES: First, survival at 2-year corrected age with or without neurosensory impairment, and second, perinatal, short-, and mid-term outcomes (survival at discharge, survival at discharge without severe morbidity) were described and compared by chorionicity. RESULTS: In the EPIPAGE 2 cohort, 1700 preterm births were included (850 twin pregnancies). In all, 1220 (71.8%) were from dichorionic (DC) pregnancies and 480 from monochorionic (MC) pregnancies. MC pregnancies had three times more medical terminations than DC pregnancies (1.67 versus 0.51%, P < 0.001), whereas there were three times more stillbirths in MC than in DC pregnancies (10.09 versus 3.78%, P < 0.001). Both twins were alive at birth in 86.6% of DC pregnancies compared with 80.0% among MC pregnancies (P = 0.008). No significant difference according to chorionicity was found regarding neonatal deaths and morbidities. Likewise, for children born earlier than 32 weeks, the 2-year follow-up neurodevelopmental results were not significantly different between DC and MC twins. CONCLUSIONS: This study confirms that MC pregnancies have a higher risk of adverse outcomes. However, the outcomes among preterm twins admitted to neonatal intensive care units are similar irrespective of chorionicity. TWEETABLE ABSTRACT: Monochorionicity is associated with adverse perinatal outcomes, but outcomes for preterm twins are comparable irrespective of their chorionicity.

Neurodevelopment at 2 years and umbilical artery Doppler in cases of very preterm birth after prenatal hypertensive disorder or suspected fetal growth restriction: EPIPAGE-2 prospective population-based cohort study.

OBJECTIVE: To investigate the association between absent or reversed end-diastolic flow (ARED) on umbilical artery Doppler ultrasound and poor neurological outcome at 2 years of age after very preterm birth associated with suspected fetal growth restriction (FGR) or maternal hypertensive disorders. METHODS: The study population comprised all very preterm (22-31 completed weeks) singleton pregnancies delivered because of suspected FGR and/or maternal hypertensive disorders that had umbilical artery Doppler and 2-year follow-up available included in EPIPAGE-2, a prospective, nationwide, population-based cohort of preterm births in France in 2011. Univariate and two-level multivariable logistic regression analyses were used to assess the association of ARED in the umbilical artery, as compared with normal or reduced end-diastolic flow, with severe or moderate neuromotor and/or sensory disability and with an Ages and Stages Questionnaire (ASQ) score below a threshold. This was defined as a score more than 2 SD below the mean in any of the five domains, at age 2, adjusting for gestational age at delivery. ASQ is used to identify children at risk of developmental delay requiring reinforced follow-up and further evaluation. Descriptive statistics and bivariate tests were weighted according to the duration of the inclusion periods. RESULTS: The analysis included 484 children followed up at 2 years of age, for whom prenatal umbilical artery Doppler ultrasound was available. Among them, 8/484 (1.6%) had severe or moderate neuromotor and/or sensory disability, and 156/342 (45.4%) had an ASQ score below the threshold. Compared with normal or reduced end-diastolic flow in the umbilical artery (n = 305), ARED (n = 179) was associated with severe or moderate neuromotor and/or sensory disability (adjusted odds ratio (OR), 11.3; 95% CI, 1.4-93.2) but not with an ASQ score below the threshold (adjusted OR, 1.2; 95% CI, 0.8-1.9). CONCLUSION: Among children delivered before 32 weeks of gestation due to suspected FGR and/or maternal hypertensive disorder who survived until 2 years of age, prenatal ARED in the umbilical artery was associated with a higher incidence of severe or moderate neuromotor and/or sensory disability. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Planned delivery route of preterm breech singletons, and neonatal and 2-year outcomes: a population-based cohort study.

OBJECTIVE: To assess whether planned route of delivery is associated with perinatal and 2-year outcomes for preterm breech singletons. DESIGN: Prospective nationwide population-based EPIPAGE-2 cohort study. SETTING: France, 2011. SAMPLE: Three hundred and ninety women with breech singletons born at 26-34 weeks of gestation after preterm labour or preterm prelabour rupture of membranes. METHODS: Propensity-score analysis. MAIN OUTCOME MEASURES: Survival at discharge, survival at discharge without severe morbidity, and survival at 2 years of corrected age without neurosensory impairment. RESULTS: Vaginal and caesarean deliveries were planned in 143 and 247 women, respectively. Neonates with planned vaginal delivery and planned caesarean delivery did not differ in survival (93.0 versus 95.7%, P = 0.14), survival at discharge without severe morbidity (90.4 versus 89.9%, P = 0.85), or survival at 2 years without neurosensory impairment (86.6 versus 91.6%, P = 0.11). After applying propensity scores and assigning inverse probability of treatment weighting, as compared with planned vaginal delivery, planned caesarean delivery was not associated with improved survival (odds ratio, OR 1.31; 95% confidence interval, 95% CI 0.67-2.59), survival without severe morbidity (OR 0.75, 95% CI 0.45-1.27), or survival at 2 years without neurosensory impairment (OR 1.04, 95% CI 0.60-1.80). Results were similar after matching on propensity score. CONCLUSIONS: No association between planned caesarean delivery and improved outcomes for preterm breech singletons born at 26-34 weeks of gestation after preterm labour or preterm prelabour rupture of membranes was found. The route of delivery should be discussed with women, balancing neonatal outcomes with the higher risks of maternal morbidity associated with caesarean section performed at low gestational age.

[Epidemiology, risk factors and child prognosis: CNGOF Preterm Premature Rupture of Membranes Guidelines]. / Épidémiologie, facteurs de risque et pronostic de l'enfant. RPC : rupture prématurée des membranes avant terme CNGOF.

OBJECTIVES: To synthetize the available evidence regarding the incidence and risk factors of preterm premature rupture of membranes (PPROM). To describe the evolution of pregnancy, neonatal outcomes and the prognosis of infants born in a context of PPROM, according to the existence of an associated intrauterine infection and to the latency duration. METHOD: Consultation of the Medline database, from 1980 to February 2018. RESULTS: PPROM before 37 and before 34 weeks' gestation occur in 2-3% and <1% of pregnancies, respectively (LE2). Although many risk factors are identified, few are modifiable, and the vast majority of patients have no risk factors (LE2). Consequently, individual prediction of the risk of PPROM and primary prevention measures have not been shown to be effective and are not recommended in clinical practice (Grade B). Most women give birth within the week following PPROM (LE2). The main complications of PPROM are prematurity, intrauterine infection and obstetric and maternal complications (LE2). Latency duration and the frequency of complications decrease with increasing gestational age at PPROM (LE2). Neonatal prognosis is largely conditioned by gestational age at birth, with no apparent over-risk of poor outcomes linked to PPROM compared to other causes of preterm birth (LE2). In contrast, intrauterine infection is associated with an increased risk of in utero fetal death (LE3), necrotizing enterocolitis (LE1) and early-onset sepsis (LE2). The association of intrauterine infection with neurological morbidity remains controversial. Prolongation of latency, from gestational age at PPROM, is beneficial for the child (LE2). CONCLUSION: PPROM is a major cause of prematurity and short- and long-term mortality and morbidity. Antenatal care is an important issue for obstetric and pediatric teams, aiming to reduce complications and adverse consequences for both mother and child.

[Preterm premature rupture of membranes: CNGOF Guidelines for clinical practice - Short version]. / Rupture prématurée des membranes avant terme : recommandations pour la pratique clinique du CNGOF ­ Texte court.

OBJECTIVE: To determine management of women with preterm premature rupture of membranes (PPROM). METHODS: Bibliographic search from the Medline and Cochrane Library databases and review of international clinical practice guidelines. RESULTS: In France, PPROM rate is 2 to 3% before 37 weeks of gestation (level of evidence [LE] 2) and less than 1% before 34 weeks of gestation (LE2). Prematurity and intra-uterine infection are the two major complications of PPROM (LE2). Compared to other causes of prematurity, PPROM is not associated with an increased risk of neonatal mortality and morbidity, except in case of intra-uterine infection, which is associated with an augmentation of early-onset neonatal sepsis (LE2) and of necrotizing enterocolitis (LE2). PPROM diagnosis is mainly clinical (professional consensus). In doubtful cases, detection of IGFBP-1 or PAMG-1 is recommended (professional consensus). Hospitalization of women with PPROM is recommended (professional consensus). There is no sufficient evidence to recommend or not recommend tocolysis (grade C). If a tocolysis should be prescribed, it should not last more than 48hours (grade C). Antenatal corticosteroids before 34 weeks of gestation (grade A) and magnesium sulfate before 32 weeks of gestation (grade A) are recommended. Antibiotic prophylaxis is recommended (grade A) because it is associated with a reduction of neonatal mortality and morbidity (LE1). Amoxicillin, 3rd generation cephalosporins, and erythromycin in monotherapy or the association erythromycin-amoxicillin can be used (professional consensus), for 7 days (grade C). However, in case of negative vaginal culture, early cessation of antibiotic prophylaxis might be acceptable (professional consensus). Co-amoxiclav, aminosides, glycopetides, first and second generation cephalosporins, clindamycin, and metronidazole are not recommended for antibiotic prophylaxis (professional consensus). Outpatient management of women with clinically stable PPROM after 48hours of hospitalization is a possible (professional consensus). During monitoring, it is recommended to identify the clinical and biological elements suggesting intra-uterine infection (professional consensus). However, it not possible to make recommendation regarding the frequency of this monitoring. In case of isolated elevated C-reactive protein, leukocytosis, or positive vaginal culture in an asymptomatic patient, it is not recommended to systematically prescribe antibiotics (professional consensus). In case of intra-uterine infection, it is recommended to immediately administer an antibiotic therapy associating beta-lactamine and aminoside (grade B), intravenously (grade B), and to deliver the baby (grade A). Cesarean delivery should be performed according to the usual obstetrical indications (professional consensus). Expectative management is recommended before 37 weeks of gestation in case of uncomplicated PPROM (grade A), even in case of positive vaginal culture for B Streptococcus, provided that an antibiotic prophylaxis has been prescribed (professional consensus). Oxytocin and prostaglandins are two possible options to induce labor in case of PPROM (professional consensus). CONCLUSION: Expectative management is recommended before 37 weeks of gestation in case of uncomplicated PPROM (grade A).

[Management of preterm labor]. / Prise en charge d'une menace d'accouchement prématuré.

OBJECTIVE: To define the management of preterm labor (MAP). METHOD: The literature search was conducted using computer databases Medline and the Cochrane Library for a period from 1969 to March 2016. RESULTS: Leukocytosis screening may be useful in case of hospitalization for Preterm labor (PTL). Its use is not routine (professional consensus). Screening for urinary tract infection by urine culture should be systematic and antibiotic treatment should be performed in cases of bacterial colonization or urinary tract infection for a period of 7 days (grade A). The vaginal swab is useful to detect a strep B and was prescribed antibiotics during labor if positive (grade A). Routine antibiotic therapy is not recommended in case of PTL (grade A). Prolonged hospitalization does not reduce the risk of preterm delivery (NP3) and is not recommended (grade B). Bed rest does not reduce the risk of PTL (NP3), increases the risk of thromboembolism (NP3), and is not recommended (grade C). After hospitalization for PTL, a regular visit by a caregiver at home may be helpful when patients belong to a precarious environment or are psychologically vulnerable (Professional consensus). The benefit of monitoring home uterine activity repeated in the aftermath of hospitalization for PTL is not shown (NP3). It is not recommended to follow-up uterine activity systematically after hospitalization for PTL (grade C). CONCLUSION: The management of PTL should be individualized, include searching and treatment of infection and avoid prolonged hospitalization or bed rest.