Isabelle Marc

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Purpose: Limited data are available on the cardiorespiratory and muscle fitness of children with acute lymphoblastic leukemia (ALL) during chemotherapy. This pilot study evaluated the safety of testing the cardiorespiratory and muscle fitness of two children with ALL at different risk levels in early chem treatment. Methods: Two girls with low- and high-risk B-cell ALL (DFCI-16-001) took part in two test sessions: T1 (induction, consolidation 1A/C) and T2 (consolidation 2). Each testing session included a maximal oxygen uptake ( V ˙ O ₂ max) exercise test, muscular strength tests, physical activity and quality of life questionnaires, and a semi-structured interview. The parents agreed to these assessments at the start of chemotherapy treatment. Results: The participants experienced no significant adverse effects from undertaking the cardiorespiratory and muscular tests, and there was no impact on their chemotherapy treatment schedule. At their post-test interview, both participants reported that thigh pain and fatigue were the most difficult part of the V ˙ O ₂ max exercise test. Regarding physical performance outcomes, both participants exhibited low scores compared to their gender, weight- and age-predicted V ˙ O ₂ max and on most strength test values. Conclusion: The physical tests were safely and successfully conducted with these two participants during early chemotherapy.

To explore whether prenatal conditions (i.e. chorioamnionitis, preeclampsia or small-for-gestational age (SGA)) affect the very preterm infant’s response to docosahexaenoic acid (DHA) on bronchopulmonary dysplasia (BPD), according to mode of delivery, an independent factor shown to modulate this association. Secondary exploratory analysis of the MOBYDIck randomized controlled trial (NCT02371460) evaluating the effect of a neonatal high-dose DHA supplementation through maternal breastmilk compared to placebo. Population was preterm infants born before 29 weeks of gestation in sixteen Canadian neonatal intensive care units. Primary outcome was physiological BPD based on pulse oximetry assessment. Secondary outcomes included “death or BPD”; “moderate-or-severe” BPD; severe BPD; death from any causes. Heterogeneity in the effect of DHA on outcomes was assessed by prenatal conditions and mode of delivery using generalized estimating equation logistic regression models. The trial intended to enroll 800 mothers but was stopped early for safety, likely making subgroup analysis underpowered. 230 mothers (271 infants) were included in DHA group and 226 mothers (252 infants) in placebo group. The association between high-dose DHA and BPD differed by chorioamnionitis status (heterogeneity P=0.04). In infants exposed to chorioamnionitis and vaginal delivery, DHA supplementation was associated with a reduced risk of physiological BPD (adjusted odds ratio, 0.18 [95% CI, 0.05 to 0.62], P=0.007). No heterogeneity was found by maternal preeclampsia (heterogeneity P=0.44) nor SGA status (heterogeneity P=0.17). Conclusion: This secondary analysis generated hypotheses for a potential differential effect of neonatal enteral high-dose DHA supplementation on BPD in very preterm infants according to chorioamnionitis exposure. What is Known: • The MOBYDIck trial reported a potential protective effect of docosahexaenoic acid (DHA) supplementation on bronchopulmonary dysplasia (BPD) in infants born vaginally, but not in those born via cesarean section. • Placenta pathologies are associated with inflammation in the infants and could affect the very preterm infant’s response to a high-dose DHA supplementation on BPD according to the mode of delivery. What is New: • This study suggests that, in infants born very preterm before 29 weeks of gestation, the association between enteral high-dose DHA supplementation in neonatal period and BPD at 36 weeks’ postmenstrual age differ according to the maternal status for chorioamnionitis at delivery.

Introduction Severe bronchopulmonary dysplasia (BPD) is a well-known factor consistently associated with impaired cognitive outcomes. Regarding reported benefits on long-term neurodevelopmental outcomes, the potential adverse effects of high-dose docosahexaenoic acid (DHA) supplementation on this short-term neonatal morbidity need further investigations in infants born very preterm. This study will determine whether high-dose DHA enteral supplementation during the neonatal period is associated with the risk of severe BPD at 36 weeks’ postmenstrual age (PMA) compared with control, in contemporary cohorts of preterm infants born at less than 29 weeks of gestation. Methods and analysis As part of an Australian–Canadian collaboration, we will conduct an individual participant data (IPD) meta-analysis of randomised controlled trials targeting infants born at less than 29 weeks of gestation and evaluating the effect of high-dose DHA enteral supplementation in the neonatal period compared with a control. Primary outcome will be severe grades of BPD (yes/no) at 36 weeks’ PMA harmonised according to a recent definition that predicts early childhood morbidities. Other outcomes will be survival without severe BPD, death, BPD severity grades, serious brain injury, severe retinopathy of prematurity, patent ductus arteriosus and necrotising enterocolitis requiring surgery, sepsis, combined neonatal morbidities and growth. Severe BPD will be compared between groups using a multivariate generalised estimating equations log-binomial regression model. Subgroup analyses are planned for gestational age, sex, small-for-gestational age, presence of maternal chorioamnionitis and mode of delivery. Ethics and dissemination The conduct of each trial was approved by institutional research ethics boards and written informed consent was obtained from participating parents. A collaboration and data sharing agreement will be signed between participating authors and institutions. This IPD meta-analysis will document the role of DHA in nutritional management of BPD. Findings will be disseminated through conferences, media interviews and publications to peer-reviewed journals. PROSPERO registration number CRD42023431063. Trial registration number NCT05915806.

Importance: High-dose docosahexaenoic acid (DHA), a long-chain polyunsaturated fatty acid, may affect the risk of bronchopulmonary dysplasia (BPD). However, high-level summative evidence supporting such clinical association in very preterm infants is lacking.Objective: To examine the association between enteral supplementation with high-dose DHA during the neonatal period and the risk of BPD in preterm infants born at less than 29 weeks’ gestation.Data Sources: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, medRxiv, and ClinicalTrials.gov were searched from inception to August 1, 2022, for eligible articles with no language restrictions.Study Selection: Randomized clinical trials (RCTs) were eligible for inclusion (1) if their interventions involved direct administration of a minimum DHA supplementation of 40 mg/kg/d or breast milk or formula feeding of at least 0.4% of total fatty acids, and (2) if they reported data on either BPD, death, BPD severity, or a combined outcome of BPD and death.Data Extraction and Synthesis: Two investigators completed independent review of titles and abstracts, full text screening, data extraction, and quality assessment using the Cochrane Risk of Bias 2.0. Risk ratios (RRs) with 95% CIs were pooled using random-effect meta-analyses.Main Outcomes and Measures: Primary outcome was BPD using trial-specific definitions, which was further stratified for RCTs that used a more stringent BPD definition based on systematic pulse oximetry assessment at 36 weeks’ postmenstrual age. Other outcomes were BPD, death, BPD severity, or combined BPD and death.Results: Among the 2760 studies screened, 4 RCTs were included, which involved 2304 infants (1223 boys [53.1%]; mean [SD] gestational age, 26.5 [1.6] weeks). Enteral supplementation with high-dose DHA was associated with neither BPD (4 studies [n = 2186 infants]; RR, 1.07 [95% CI, 0.86-1.34]; P = .53; I² = 72%) nor BPD or death (4 studies [n = 2299 infants]; RR, 1.04 [95% CI, 0.91-1.18]; P = .59; I² = 61%). However, an inverse association with BPD was found in RCTs that used a more stringent BPD definition (2 studies [n = 1686 infants]; RR, 1.20 [95% CI, 1.01-1.42]; P = .04; I² = 48%). Additionally, DHA was inversely associated with moderate-to-severe BPD (3 studies [n = 1892 infants]; RR, 1.16 [95% CI, 1.04-1.29]; P = .008; I² = 0%).Conclusions and Relevance: Results of this study showed that enteral supplementation with high-dose DHA in the neonatal period was not associated overall with BPD, but an inverse association was found in the included RCTs that used a more stringent BPD definition. These findings suggest that high-dose DHA supplementation should not be recommended to prevent BPD in very preterm infants.

The status of breastfeeding practices remains unsatisfactory across China, but regional differences persist. However, disaggregated data for specific provinces are limited. This representative survey determined the status of breastfeeding and factors associated with breastfeeding practices in Shanghai. The questionnaire was designed in compliance with indicators for assessing infant and young child-feeding practices defined by the World Health Organization and the United Nations Children’s Fund (UNICEF). A total of 2665 children aged two years and younger (0–730 days) were investigated, among whom 1677 were aged under six months. The early initiation of breastfeeding (EIBF) rate was 60.3%. Among children aged under six months, 43.4% were exclusively breastfed (EBF). The univariate regression analysis showed that the EBF rate was influenced by multiple factors, including individual, socioeconomic, workplace and employment, and health system. The subsequent multivariate analysis suggested that mothers with a higher rate of EBF shared the following characteristics: intention to breastfeed during pregnancy, breastfeeding knowledge, and higher satisfaction with support through the healthcare system after delivery. The rate of EBF in Shanghai is over 40%, and supporting breastfeeding requires measures at multiple levels, including individual attributes, women’s work and employment conditions, breastfeeding knowledge, and health services.

Introduction Docosahexaenoic acid (DHA) supplementation in the neonatal period has been proposed to prevent bronchopulmonary dysplasia (BPD) in very preterm infants. We aim to determine the effects of an enteral supplementation with high doses of DHA on the risk for BPD at 36 weeks’ postmenstrual age (PMA) in very preterm infants born less than 29 weeks’ gestation compared with a control. Methods and analysis We will conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) searching PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, MedRxiv, ClinicalTrials.gov (up to 1 November 2021) as well as reference lists and citations of included articles and previous reviews. RCTs targeting infants born less than 29 weeks’ gestation and evaluating the effect of high doses of DHA enteral supplementation in the neonatal period compared with a control will be eligible. Primary outcome will be BPD defined as the need for oxygen and/or ventilation at 36 weeks’ PMA. Two authors will independently screen for inclusion, extract data and assess data quality using the Cochrane instrument (risk-of-bias tool 2.0). We will perform meta-analysis using random effects models. Prespecified subgroup analyses are planned for the infant gestational age and sex, the marine source of DHA, mode of administration and duration of exposure. Sensitivity analysis will be performed according to the accuracy of the BPD definition (ie, physiological definition) and according to the risk of bias of the RCTs. Ethics and dissemination This protocol for a systematic review and meta-analysis does not require ethics approval, as no primary data are collected. This study will assess the effectiveness of high doses of enteral DHA supplementation on BPD and provide evidence to clinicians and families for decision-making. Findings will be disseminated through conferences, media interviews and publications to peer review journals. PROSPERO registration number CRD42021286705.