Publications

Abstract

Background: Very preterm children are at greater risk of academic difficulties (AD). Some of them start school a year earlier than anticipated during pregnancy due to being born preterm. The aim of this study was to analyze the relationship between neurodevelopment, school-entry age, and AD at age seven.

Method: AD were assessed at age seven in children born before 33 weeks of gestation between January 1st, 2007 and December 31, 2014 and enrolled in LIFT cohort. To analyze the relationship between school-entry age and AD, we used generalized equations with adjustment for perinatal, socio-economic factors, and neurodevelopment assessed by Age Stages Questionnaire (ASQ) at 5 years. Moreover, we used Global Scholar Adaptation (GSA) score to evaluate the school adaptation.

Results: 2599 children were in routine schooling. Entering school a year earlier was observed in 597 (23.0 %). AD was known for 1943/2599 (74.8 %). Starting school a year earlier was associated with an increased rate of AD: 35.4 % in the exposed group versus 20.2 % in the non-exposed group, with a relative risk of 1.76 (95 % CI: 1.48; 2.08). Both starting school a year earlier and ASQ at 5 years old were independently associated with the GSA score at age 7: standardized β = -0.15 (95 % CI:-0.10;-0.20) and 0.40 (95 % CI: 0.35; 0.45) respectively.

Conclusion: Starting school a year earlier than anticipated during pregnancy was associated with an increased rate of AD at age 7 in children born very preterm, independently of their neurodevelopment at age 5 assessed by ASQ. Basing school entry age on corrected age seems appropriate to mitigate this risk.

Abstract

Aim: Prematurity is a risk factor for strabismus, but the roles of intermediate factors like retinopathy of prematurity (ROP) and neurological lesions are less understood. We aimed to identify neonatal risk factors for strabismus at age 5.5 in preterm children.

Methods: Data were extracted from the étude épidémiologique sur les petits âges gestationnels 2 cohort, a French prospective population-based study of preterm children born in 2011 with gestational age of 34 weeks or less. Strabismus was recorded during a medical interview at 5.5 years. Using a directed acyclic graph, intermediate and confounding factors were identified. Total and direct effects of gestational age on strabismus risk were analysed using generalised estimating equation.

Results: Among 2419 children assessed, 274 (52.6% male) presented strabismus at 5.5 years. The direct effect of gestational age remained significant after adjustment (p < 0.001). In the complete imputed model: maternal smoking during pregnancy (odds ratio, OR 1.8; 95% confident interval, 95% CI 1.3-2.6), neonatal severe cerebral lesions (OR 2.9, 95% CI 1.8-4.6) and severe ROP (OR 4.2, 95% CI 1.9-9.0) were independent risk factors.

Conclusion: Special attention is needed regarding strabismus screening at age 5.5 in preterm children, even without severe cerebral lesions and ROP. Smoking cessation during pregnancy should be encouraged.

Abstract

Aim: Healthcare givers are exposed to stress and therefore are at risk of the development of pathologies. We aimed to provide recommendations regarding psychosocial risks such as stress, moral distress, burnout syndrome or secondary stress syndrome in neonatal care units to best support neonatal healthcare givers.

Methods: We searched PubMed for articles published from 1 January 2017 to 1 December 2023 by using the keywords burnout OR (moral and distress) AND neonatal unit. Recommendations were developed after internal and external review by a multidisciplinary group including 15 professionals and parent representatives.

Results: We identified 207 studies and developed 15 recommendations based on 118 eligible studies. Recommendations to support neonatology healthcare givers were developed for the individual level, the collective or department level to organise the environment, the training of the team with communication sessions and team cohesion; and the institutional level to respect and organise working time.

Conclusion: Psychosocial risks have consequences for the neonatal healthcare givers themselves and possibly those being cared for. To date, prevention, screening and treatment have been insufficiently developed and explored. In this context, an overall institutional review of the chosen care model is needed.

Abstract

The short-term respiratory consequences of small for gestational (SGA) are only partially known. Our aim was to compare the early respiratory features between SGA and appropriate for gestational age (AGA) in very preterm infants. We conducted a secondary analysis of the French prospective EPIPAGE-2 cohort. Eligible children were those born alive before 32 weeks’ gestation. The exposed group consisted of children with SGA. The unexposed group consisted of AGA children. SGA and AGA children were randomly matched in a ratio of 1:1 on the same gestational age and sex. Primary outcomes were age at final extubation and age at weaning from any respiratory support. Among 3.964 very preterm from the EPIPAGE2 cohort, 1123 SGA and 1123 AGA very preterm children were included in the study. The median gestational age was 30.0 weeks (interquartile range 28.0-31.0) in both groups. The median birthweight was 1440 g (1138-1680) in the AGA group and 1000 g (780-1184) in the SGA group. Invasive mechanical ventilation was less common in the SGA than in the AGA group: 68.6% (770/1123) versus 72.0% (808/1062), odds ratio 0.85 (95% CI [0.72-1.00]). In cases of mechanical ventilation, median age at final extubation was 4 days (1-23) and 2 days (1-9) in the SGA and AGA groups. Median postmenstrual age at weaning from any respiratory support was 33.4 weeks (31.7-35.9) in the SGA group and 32.4 weeks (31.4-34.3) in the AGA group.

Conclusion: SGA is associated with delayed extubation and respiratory support weaning.

What is known: • Small for gestational age concerns more than 30% of very preterm children. • The condition is strongly associated with increased neonatal mortality and morbidity, including bronchopulmonary dysplasia.

What is new: • Small for gestational age is associated with delayed extubation and respiratory support weaning in very preterm children. • Shortening invasive mechanical ventilation as much as possible is a crucial issue in this population to try to reduce the risk of bronchopulmonary dysplasia.

Abstract

Prophylactic administration of low-dose hydrocortisone, at replacement dosage, targets inability of extremely low gestational age neonates (ELGANs) to respond to postnatal stress due to adrenal glands immaturity and is intended to prevent serious complications such as death and bronchopulmonary dysplasia (BPD). Increasing evidence from systematic reviews shows that prophylactic hydrocortisone reduces pre-discharge mortality, improves survival without BPD, favors patent ductus arteriosus (PDA) closure, and may have beneficial effects on cardiovascular stability and urine output. In contrast, an increased risk of spontaneous intestinal perforation when prophylactic hydrocortisone is combined with indomethacin and late-onset sepsis, particularly in infants of 24-25 weeks of gestation, have been reported as major adverse events. No significant negative impact on long-term neurodevelopmental outcomes following prophylactic hydrocortisone exposure was observed. Recent real-world data, despite their intrinsic methodological limitations, generally confirm the benefits observed in clinical trials, even with additional potential benefits and without increased adverse events. Ongoing challenges and questions discussed in this invited review relate to the best population to treat, optimal timing and duration of treatment, and potential barriers to implementation due to evolving knowledge and guidelines. IMPACT STATEMENT: Prophylactic low-dose hydrocortisone improves survival without BPD in infants born extremely preterm. Recent real-world data generally confirm the benefits observed in clinical trials, even with additional potential benefits and without increased adverse events. Unanswered questions remain about optimal timing and duration of treatment, and potential barriers to implementation due to evolving knowledge and guidelines.

Abstract

Aim: Infants born very preterm spend their early postnatal life in a neonatal intensive care unit, where irregular and unpredictable sounds replace the structured and familiar intrauterine auditory environment. Music interventions may contribute to alleviate these deleterious effects by reducing stress and providing a form of environmental enrichment.

Material and methods: This was an ancillary study as part of a blinded randomised controlled clinical trial entitled the effect of music on preterm infant’s brain development. It measured the impact of music listening on the autonomic nervous system (ANS), we assessed heart rate variability (HRV) through high-resolution recordings of heart rate monitoring, at three specific postmenstrual ages in premature infants.

Results: From 29 included subjects, 18 were assessed for complete HRV dataset, including nine assigned to the music intervention and nine to the control group. Postmenstrual age appeared to be the main factor influencing HRV from 33 weeks to term equivalent age. Further analyses did not reveal any detectable effect of music intervention on ANS response.

Conclusion: This study found that ANS responses were not modified by recorded music intervention in very preterm infants during wakefulness or sleep onset. Further research is warranted to explore other factors influencing ANS development in this population.

Keywords: autonomic nervous system; heart rate variability; music intervention; neonatal intensive care unit; preterm infants.

Abstract

Proteins play a crucial role in determining disease states in humans, making them prime targets for the development of diagnostic sensors. The developed sensor array is used to investigate global proteomic changes by fingerprinting multifactorial disease states in model urine simulating phenylketonuria and in serum from preeclamptic pregnant women. Here, we report a fluorescence-based chemical sensing array that exploits the host-guest interaction between cucurbit[7]uril (CB[7]) and fluorescent triphenylamine derivatives (TPA) to detect a range of proteins. Using linear discriminant analysis, we identify fluorescence fingerprints of 14 proteins with over 98% accuracy in buffer and human serum. The array is optimized on an automated droplet microfluidic-based platform, for high-throughput sensing with controlled composition and lower sample volumes. This sensor enables the discrimination of proteins in physiological buffer and human serum, with promising applications in disease diagnosis.

Abstract

Background: Pertussis vaccination in young mothers aims to protect neonates through cocooning. We estimated pertussis vaccination coverage (VC) in women at two months postpartum in France in 2021, and the proportion of women who got vaccinated in the first two months postpartum; associated determinants were studied.

Methods: We used data from the 2021 National Perinatal Surveys conducted in metropolitan France (ENP 2021) and French overseas territories (ENP-DROM 2021). Multivariate poisson regressions were employed to study the following determinants: age, educational level, monthly household income, socio-professional situation, birth country, parity, health professional who monitored pregnancy, influenza vaccination during pregnancy, region of residence, prenatal care consultations, having health insurance, having a partner, and having a chronic pathology. Results were weighted.

Results: The study sample comprised 7999 women. Estimated pertussis VC at two months postpartum was 66.8 % (95 %CI [65.5-68.0]). VC was significantly lower in i) unemployed women (vs. executives/managers, intermediate and higher intellectual professionals), ii) those on low income (vs. high), and iii) those with two or more children (vs. primiparous). It was significantly higher in i) women born in France, ii) those vaccinated against influenza during pregnancy, iii) those who received pre-natal care from a private midwife, and iv) those with more prenatal consultations. The proportion of women vaccinated against pertussis in the two-month postpartum period (33.4 % [31.7-35.9]) was significantly lower in i) women on low incomes, ii) unemployed women, iii) women with health insurance, and iv) multiparous women. It was significantly higher in those vaccinated against influenza during pregnancy.

Discussion – conclusion: Pertussis VC in women at two months postpartum in 2021 was insufficient and was marked by social and territorial inequalities in health. Vaccination for pregnant women has been recommended in France since 2022. A study monitoring the impact of this new recommendation is essential.

Summary

Background

Pregnancy-associated haematological malignancy is a rare event; therefore, data available to guide the treatment are scarce. We aimed to evaluate the incidence, overall survival, and maternal morbidity and mortality of women with pregnancy-associated haematological malignancies.

Methods

We conducted a nationwide observational cohort study using the French National Healthcare Data System (SNDS), a health-care administrative database covering up to 99% of the French population. We included all pregnancies in France ending between Jan 1, 2012, and Dec 31, 2022. Pregnancies with terminations or miscarriages managed on an outpatient basis, and women with a history of haematological malignancies before pregnancy were excluded. A Cox proportional hazards model was used to assess overall survival, defined as the date of haematological malignancy diagnosis to either death or the end of the study follow-up, in the haematological malignancy during pregnancy group (pregnancies with a diagnosis of haematological malignancy during pregnancy) compared with the haematological malignancy post-pregnancy group (pregnancies with a diagnosis of haematological malignancy in the year following pregnancy). Severe maternal morbidity was compared in the haematological malignancy during pregnancy group versus the reference group (pregnancies without a history of haematological malignancy or a diagnosis of pregnancy-associated haematological malignancy). Births were classified as very preterm (<32 weeks of pregnancy), preterm (32–36 weeks), and term (≥37 weeks) and compared in the haematological malignancy during pregnancy group versus the reference group. Inverse probability weighting (IPW) was used for confounder adjustment, using maternal age (categorised), comorbidities, socioeconomic status, and year of delivery (as a category).

Findings

Of 9 996 523 pregnancies in 5 995 235 women, 1366 pregnancy-associated haematological malignancies were identified: 413 during pregnancy (4·13 per 100 000 pregnancies) and 953 (9·53 per 100 000 pregnancies) within 12 months of the end of pregnancy (post-pregnancy). No significant differences in overall survival were observed between the haematological malignancy during and post-pregnancy groups across all types of haematological malignancy (IPW-adjusted hazard ratio 0·91 [95% CI 0·62–1·34], p=0·63), specifically for Hodgkin lymphoma (0·56 [0·07–4·53], p=0·59), aggressive B-cell non-Hodgkin lymphoma (0·52 [0·12–2·38], p=0·40), and acute leukaemia alone (0·84 [0·50–1·41], p=0·51). Severe maternal morbidity was more frequent in the haematological malignancy during pregnancy group than in the reference group (86 [26·2%] of 328 completed pregnancies vs 120 335 [1·5%] of 7 945 909 completed pregnancies; IPW-adjusted odds ratio 22·71 [95% CI 17·72–29·10], p<0·0001). We observed an increase in very preterm birth (32 [9·8%] vs 92 712 [1·2%]; IPW-adjusted odds ratio 11·90 [95% CI 7·91–17·91], p<0·0001) and preterm birth (116 [35·4%] vs 430 472 [5·4%]; 11·76 [9·34–14·81], p<0·0001) in the haematological malignancy during pregnancy group compared with the reference group.

Interpretation

This nationwide observational study examines pregnancy-associated haematological malignancies in France, revealing no significant difference in overall survival between women diagnosed during pregnancy and post-pregnancy. Our data highlight an increased frequency of severe maternal morbidity and obstetric complications among women diagnosed during pregnancy. Notably, the study underscores the necessity for specialised care to manage these complex cases effectively.

Abstract

Introduction: This study aimed to evaluate the agreement between the proteinuria/creatinuria (P/C) ratio and the traditional 24-hour proteinuria measurement for proteinuria levels above 3 g/24h in pregnant patients with preeclampsia. Additionally, we assessed whether high levels of each measurement are predictive of adverse maternal and neonatal outcomes.

Material and methods: We conducted a monocentric retrospective study of pregnant patients hospitalized for preeclampsia between January 1, 2019, and November 11, 2020. The primary outcome was a composite measure of adverse maternal outcomes associated with preeclampsia, and the secondary outcome focused on adverse neonatal outcomes. Agreement between high levels of 24-hour proteinuria and the P/C ratio was evaluated using Cohen’s Kappa. Maternal and neonatal outcomes were compared across three groups: those with neither, one, or both high proteinuria levels (24-hour proteinuria ≥ 3 g/24h and/or P/C ratio ≥ 300 mg/mmol). Logistic regression, adjusted for confounders, analyzed associations between measures and outcomes, with ROC curves and AUC calculated for predictive models.

Results: We found a strong correlation between 24-hour proteinuria and P/C ratio, with 95.1% agreement at the threshold of 3 g/24h and 300 mg/mmol, respectively (Kappa = 0.87, p < 0.01). Both measurements were associated with an increased risk of adverse maternal (aOR 6.78 [2.47-18.63]) and neonatal (aOR 7.00 [1.56-31.31]) outcomes.

Discussion: This study demonstrated a strong agreement between the P/C ratio ≥ 300 mg/mmol and 24-hour proteinuria ≥ 3 g/24h, both associated with an increased risk of adverse perinatal outcomes, with the P/C ratio offering a quicker, simpler alternative for managing preeclampsia.