Publications

Abstract

The mode of delivery in cases of very preterm or extremely preterm breech presentation remains a matter of debate. Available randomized trials are too few and underpowered to provide a definitive answer, and most of the evidence comes from observational, hospital-based or population-based studies, often limited by bias, particularly indication bias. Practices vary widely depending on teams and institutional policies. Analyses from different cohorts, including EPIPAGE 1 and 2, show no clear superiority of planned cesarean section over planned vaginal delivery with respect to neonatal mortality, severe morbidity, or long-term sequelae, although a rare but documented risk of death due to entrapment of the aftercoming head is described, especially in low-birth-weight infants. A meta-analysis published in 2024 reported, for breech singletons, a significant reduction in mortality with cesarean delivery, whether performed or planned, a result largely driven by two retrospective studies with a high risk of bias. These findings highlight the need to balance neonatal risks against maternal complications (and neonatal risks in subsequent pregnancies) related to cesarean section at such an early gestational age, without any delivery mode being clearly recommended.

Abstract

Spontaneous preterm births, particularly those occurring before 32 weeks of gestation, are a major cause of neonatal morbidity. In women with a prior spontaneous preterm birth, the risk of recurrence is estimated at around 30%. Two main preventive strategies are proposed: prophylactic cerclage, performed before 16 weeks, and cervical ultrasound surveillance with ultrasound-indicated cerclage in case of cervical shortening. In the absence of a standardized clinical definition of cervical insufficiency, comparisons between these strategies are limited by three main factors: indication bias, as women at highest risk are more likely to undergo cervical ultrasound monitoring; the lack of a standardized clinical definition of cervical insufficiency, which leads to the inclusion of lower-risk women and dilutes potential benefits; and the relative rarity of the condition, which reduces the statistical power of available studies. Meta-analyses cannot correct for these limitations. The absence of a demonstrated difference despite indication bias suggests that classical cases of cervical insufficiency may benefit more from prophylactic cerclage. Future research should also consider medico-economic and psychological aspects. In conclusion, for women with an isolated history of spontaneous preterm birth, the choice between prophylactic cerclage and ultrasound surveillance should be individualized, taking into account clinical history, patient preferences, and available resources.

Abstract

Preterm birth is a major cause of perinatal morbidity and mortality. In France, about 7% of births occur before 37 weeks of gestation, nearly two-thirds of which are spontaneous. Preterm labor (PTL), defined as the combination of uterine contractions and cervical changes between 22 and 37 weeks, represents the most frequent condition leading to prematurity. However, half of the women hospitalized for PTL ultimately deliver at term, highlighting the need for reliable tools to identify those truly at risk. Transvaginal ultrasound measurement of cervical length is currently the reference exam. Its negative predictive value is excellent, but its positive predictive value remains limited and depends on the threshold used. Other ultrasound parameters, such as internal os funneling or the presence of intra-amniotic sludge, have been investigated, though with variable results. Biomarkers identified in cervicovaginal secretions represent an alternative or complementary approach. Fetal fibronectin, initially assessed qualitatively, is now studied quantitatively, allowing sensitivity or specificity to be adjusted depending on the chosen threshold. PAMG-1 shows higher specificity, but its use is not recommended by most professional societies. Maternal serum biomarkers, particularly those related to inflammation or infection, are also being studied, though only on an exploratory basis. Finally, several algorithms combining clinical data, ultrasound, and biomarkers have shown promising results in predicting the risk of short-term delivery. The challenge remains to optimize the management of PTL by identifying all women at high risk, while limiting the iatrogenic effects of unnecessary hospitalizations.

Abstract

This study presents a summary of the results from two cohorts of children born very preterm, EPIPAGE-2 (Epidemiological Study of Small Gestational Ages) in France, and EPICE-SHIPS (“Effective Perinatal Intensive Care in Europe”) in Europe. In 2011, these two cohorts collected data on very preterm infants and their families between birth and age 10. The survival of very preterm infants has improved over the past 25 years, but with significant differences between countries, particularly for extreme prematurity. At preschool age in France, 28% of children born at 24-26 weeks, 19% of those born at 27-31 weeks, and 12% of children born at 32-34 weeks had moderate to severe impairments, compared with 5% of children born at term. 52% of children born at 24-26 weeks of gestation received specialized care, compared to 33% at 27-31 weeks, 26% at 32-34 weeks, and 25% at term. Among children with moderate to severe disabilities, 30-40% did not receive any specialized care. In Europe, the percentage of children receiving such care varied from 28% to 50% depending on the European region. These cohorts provided original data on the prognosis of children born very preterm, its evolution over time, and the care offered. They helped to redefine certain practices, healthcare organization methods and public health policies. Despite the progress made, these children, who represent only 1% of births, account for 50% of perinatal deaths and 50% of disabilities associated with the perinatal period. Nearly 15 years after EPIPAGE-2 and EPICE, the question arises of re-evaluating the care and prognosis for these children.

Abstract

The aim of this review is to gather the most recent data on the association between intrauterine inflammation and neurodevelopmental disorders in preterm infants. Two major methodological challenges will be emphasized: first, the heterogeneity of definitions of intrauterine inflammation; and second, the heterogeneity of study populations, in which the causes of preterm birth (spontaneous labor, preterm premature rupture of membranes, maternal hypertensive disorders, etc.) are not always distinguished. These elements introduce a risk of confounding bias and partly explain the divergence between studies. In the short term, intrauterine inflammation is associated with an increased risk of early-onset sepsis and necrotizing enterocolitis. However, the effects on respiratory and neurological outcomes are less clear, and whether an association exists remains controversial. In the longer term, in populations homogeneous with respect to the cause of prematurity, clinical chorioamnionitis has been associated with an increased risk of cerebral palsy at 2 years, a risk further amplified when combined with histological chorioamnionitis. However, this risk of cerebral palsy does not appear to persist beyond 5 years, and no major association has been reported on cognitive, sensory, coordination, or behavioral functions. Regarding isolated histological chorioamnionitis, most studies conducted on homogeneous populations do not report an association with neurodevelopmental disorders. Nevertheless, some suggest that severe inflammation, particularly in the presence of a fetal inflammatory response, may increase the risk of neurodevelopmental impairment. In conclusion, while intrauterine inflammation is associated with increased neonatal morbidity, its long-term impact on neurodevelopment appears limited and dependent on the severity of the inflammation. These findings highlight the importance of conducting longitudinal studies on homogeneous populations to refine our understanding of developmental trajectories in preterm infants.

Abstract

Retrospective foreign studies conducted using data from medical-administrative registers have all reported an increase in neonatal mortality and morbidity associated with vaginal delivery, mainly for the second twin. However, these studies suffer from major methodological flaws: lack of comparison according to the planned route of delivery, difficulty in distinguishing extreme prematurity from moderate or late prematurity, lack of adjustment for the most important confounding factors, so that their results do not allow any conclusion regarding a protective effect of cesarean section. Conversely, 3 high-quality French studies, including 2 prospective studies, report no benefit associated with cesarean section in women with preterm labor or premature rupture of membranes. In these 3 studies, even if the differences are not significant, severe neonatal morbidity is lower or survival without severe neonatal morbidity is higher in the planned vaginal delivery group compared to the planned cesarean group. In conclusion, there is no scientific evidence to support any protective effect of elective caesarean section in cases of spontaneous prematurity before 32 weeks of gestation. Therefore, planned vaginal delivery should be the preferred option in France.

Abstract

Extremely premature infants (22-26 weeks) are at high risk of neonatal death, severe morbidity, and disability. The survival of these infants is essentially linked to the obstetrical-pediatric team’s willingness to provide intensive care. Numerous studies show that this increased survival rate in cases of willingness to actively manage them is not accompanied by an increased risk of morbidity and psychomotor delay in the longer term. The great variability in antenatal practices for the management of extremely premature infants reflects the confusion among medical teams who, in the absence of consensus and formalized decision-making processes, end up making management decisions that are at best based on local habits, and at worst on the individual habits of the attending clinician. This variability in practices across centers poses a problem of equity. Thus, in our country, practices and outcomes vary greatly depending on the child’s place of birth. Intensive antenatal care rates for these children vary from 22 to 61% depending on the region. One consequence is a survival rate in France that is much lower than in other countries. Survival in the USA, Great Britain, Japan, Australia, and Sweden is 10 to 50% higher than in France. To improve this situation, new principles have been proposed: administration of corticosteroid therapy independently of treatment, prognostic assessment not based solely on gestational age, and collective decision-making on treatment outside of an emergency setting, and consensus on the information to be provided to parents before informing them and seeking their opinions. This approach requires consistency in care before, during, and after birth and relies on close obstetric-pediatric collaboration. This new organization is being tested in the PREMEX Cluster randomized trial involving 25 perinatal networks in France, the results of which will be available in 2026.

Abstract

Objective: To explore term mortality rates in relation to rates of early-term birth (gestational ages 37 + 0 to 38 + 6 weeks), regarded as a proxy indicator of practices of elective birth by induction or caesarean.

Design: Ecological study using national birth data.

Setting: 28 European countries.

Population: Births ≥ 37 weeks between 2015 and 2020.

Methods: Aggregated data on live and stillbirths by completed week of gestation was compiled from routine sources in the Euro-Peristat network. Countries were divided into three groups based on their percentages of early-term births using terciles (high, medium and low) and mortality rates were compared between groups with random-effects meta-analysis of proportions.

Main outcome measures: Stillbirths (antepartum or intrapartum fetal death) and perinatal death (stillbirth or early neonatal death) per 1000 total births ≥ 37 weeks.

Results: Early-term birth rates ranged from 17.8% (Iceland) to 49.1% (Cyprus), with terciles being < 21%, 21%-27%, and > 27%. Post-term birth rates were low in countries with higher early-term birth rates. The pooled stillbirth rate ≥ 37 weeks was 1.28 per 1000 total births (95% CI: 1.13-1.46) in the lowest tercile and 1.05 (95% CI: 0.95-1.16) in the highest (p = 0.05), but prediction intervals were wide reflecting heterogeneity within groups. No evidence of difference was seen between perinatal mortality rates by tercile (p = 0.71).

Conclusion: On average, the stillbirth rate was lower in countries where early-term birth rates were highest, but no difference was found in perinatal mortality rates. Heterogeneity was high within groups.

Abstract

The incidence of haematological malignancies during pregnancy ranges from 4·0 to 15·8 cases per 100 000 pregnancies, with Hodgkin lymphoma, acute leukaemia, and aggressive B-cell non-Hodgkin lymphoma being the most frequent subtypes. Although survival rates are similar to those in patients who are not pregnant with similar disease profiles, pregnant women face higher risks of maternal morbidity, along with adverse obstetric and neonatal outcomes. Their management, therefore, requires a carefully balanced approach that minimises obstetric risks and ensures effective oncological control. Physiological adaptations of pregnancy can obscure the clinical presentation of sepsis, modulate the course of infections, and, through altered pharmacokinetics, complicate antimicrobial therapy. Safety data on antimicrobials are scarce and concerns about teratogenicity further constrain therapeutic decisions. As a result, infection management in pregnant women requires tailored approaches to diagnosis, antimicrobial therapy, and fetal monitoring. This Review summarises the physiological changes influencing infection risk and treatment efficacy in pregnant women with haematological malignancies; it outlines key challenges in prevention and management and identifies crucial knowledge gaps to guide practice and research in this complex interplay.

Abstract

Importance: Progress in perinatal care has improved survival for children born very preterm (VPT), but these children remain at higher risk of cognitive impairment compared with children born at term.

Objective: To synthesize cohort studies on childhood cognitive ability following VPT birth to investigate trends over time.

Data sources: All studies from 5 previous meta-analyses of VPT birth and cognition published before 2019 were included, and PubMed, Web of Science, and PsycInfo were searched for new studies published up to June 2024.

Study selection: Studies reporting IQ scores of children (aged <18 years) born VPT (<32 weeks’ gestational age [GA] or birth weight <1500 g) with a term-born comparison group were included.

Data extraction and synthesis: Two reviewers independently selected studies, extracted data, and evaluated study quality using a modified version of the Newcastle-Ottawa Scale. Unique cohorts were identified to avoid duplicate measures from studies on the same children.

Main outcomes and measures: The standardized mean difference (SMD) of IQ scores between VPT-born and term-born children was calculated, and mixed-effects metaregression was used to investigate linear and nonlinear associations between median birth year and the SMD. The main analysis focused on cohorts with IQ measured between 4 and 7 years of age to allow comparison at similar assessment ages. Secondary analyses were conducted in all cohorts using IQ obtained at the latest assessment age.

Results: A total of 257 studies reported data from 131 cohorts of 25 746 individuals born from 1977 to 2016 (15 548 born VPT and 10 198 at term). In the 61 cohorts assessed at age 4 to 7 years (13 842 children born between 1977 and 2014 [8847 born VPT and 4995 at term]; mean [SD] GA, 28.2 [1.7] weeks for the VPT cohorts), IQ was lower for VPT-born children compared with term-born children (SMD = -0.88; 95% CI, -0.97 to -0.79). The linear model showed no association with birth year (β = -0.002; 95% CI,-0.012 to 0.008). Three types of nonlinear models were fit, with no nonlinear associations observed. Adjustment for GA and study characteristics did not change the results (β = -0.001; 95% CI, -0.013 to 0.011). Secondary analysis of 131 cohorts found a similar difference between VPT and term groups (SMD = -0.84; 95% CI, -0.90 to -0.79), with no time trend (β = 0.001; 95% CI, -0.005 to 0.007).

Conclusions and relevance: On average, children born VPT had significantly lower IQ scores than term-born children, and this deficit did not decrease in studies conducted over 4 decades