Continuous Deep Sedation Until Death of Children at the End of Life: French Physicians' Opinions.

Objectives: To evaluate physicians' opinions concerning continuous deep sedation until death (CDSUD) and implementation of Claeys-Leonetti; a law intended to be applicable to all patients, but without a specific framework for children thus giving rise to ethically and legally complex situations. The secondary objective was to identify if physicians' characteristics could influence their opinions. Study Design: This was a national, multicenter, noninterventional cross-sectional survey from January 30, 2020, until March 1, 2020. The target population consisted of French physicians involved in children's end-of-life situations. The validated questionnaire explored respondents' characteristics and their opinions on four hypothetical pediatric clinical cases. Results: Analysis was conducted on 391 respondents. The oncological situation was more easily recognized as end of life compared with the neurological pathology (77% vs. 40.4%). Dependence on mechanical ventilation was another major factor influencing physicians in identifying end-of-life situations. Physicians clearly recognized the difference in intention between CDSUD and euthanasia. They accepted to implement CDSUD more easily in newborns. The withdrawal of artificial nutrition and hydration gave rise to divergent opinions. Respondents were in favor of adolescents' decision-making autonomy and their access to drafting advance directives. The child's best interest prevailed in case of objection by parents, except in situations outside the law's framework or in cases of disagreement within the health care team. Conclusion: Results of our study showed differences in the interpretation of the law concerning the CDSUD application framework and provide elements for reflection, which may ultimately contribute to the development of specific guidelines in CDSUD in children at the end of life.

Circumstances, causes and timing of death in extremely preterm infants admitted to NICU: The EPIPAGE-2 study.

AIM: To describe the circumstances, causes and timing of death in extremely preterm infants. METHODS: We included from the EPIPAGE-2 study infants born at 24-26 weeks in 2011 admitted to neonatal intensive care units (NICU). Vital status and circumstances of death were used to define three groups of infants: alive at discharge, death with or without withholding or withdrawing life-sustaining treatment (WWLST). The main cause of death was classified as respiratory disease, necrotizing enterocolitis, infection, central nervous system (CNS) injury, other or unknown. RESULTS: Among 768 infants admitted to NICU, 224 died among which 89 died without WWLST and 135 with WWLST. The main causes of death were respiratory disease (38%), CNS injury (30%) and infection (12%). Among the infants who died with WWLST, CNS injury was the main cause of death (47%), whereas respiratory disease (56%) and infection (20%) were the main causes in case of death without WWLST. Half (51%) of all deaths occurred within the first 7 days of life, and 35% occurred within 8 and 28 days. CONCLUSION: The death of extremely preterm infants in NICU is a complex phenomenon in which the circumstances and causes of death are intertwined.

Neonatal Care Unit Interventions on Preterm Development.

Prematurity is becoming a real public health issue as more and more children are being born prematurely, alongside a higher prevalence of neurodevelopmental disorders. Early intervention programs in Neonatal Intensive Care Units (NICUs) correspond to these uni- or multi-sensorial solicitations aiming to prevent and detect complications in order to support the development of preterm infants. This article aims to distinguish sensory intervention programs according to the gradient of the type of solicitations, uni- or multi-modal, and according to the function of the person who performs these interventions. Uni-sensorial interventions are essentially based on proprioceptive, gustatory, or odorant solicitations. They allow, in particular, a reduction of apneas that support the vegetative states of the preterm infant. On the other hand, the benefits of multi-sensory interventions seem to have a longer-term impact. Most of them allow the support of the transition from passive to active feeding, an increase in weight, and the improvement of sleep-wake cycles. These solicitations are often practiced by caregivers, but the intervention of parents appears optimal since they are the main co-regulators of their preterm child's needs. Thus, it is necessary to co-construct and train the parents in this neonatal care.

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.

Impact of Early Hemoglobin Levels on Neurodevelopment Outcomes of Two-Year-Olds in Very Preterm Children.

OBJECTIVE: To evaluate, in very preterm infants, the hemoglobin (Hb) levels during the first 24 h and the neurodevelopment outcomes at 24 months of corrected age. DESIGN, SETTING, AND PATIENTS: We conducted a secondary analysis of the French national prospective and population-based cohort EPIPAGE-2. The eligible study participants were live-born singletons who were born before 32 weeks of gestational age, with early Hb levels who were admitted to the neonatal intensive care unit. MAIN OUTCOME MEASURES: The early Hb levels for an outcome survival at 24 months of corrected age without neurodevelopmental impairment were measured. The secondary outcomes were survival at discharge and without severe neonatal morbidity. RESULTS: Of the 2158 singletons of <32 weeks with mean early Hb levels of 15.4 (±2.4) g/dL, 1490 of the infants (69%) had a follow-up at two years of age. An early Hb of 15.2 g/dL is the minimum receiving operating characteristic curve at the 24 months risk-free level, but the area under the curve at 0.54 (close to 50%) indicates that this rate was not informative. In logistic regression, no association was found between early Hb levels and outcomes at two years of age (aOR 0.966; 95% CI [0.775-1.204]; p = 0.758) but rather there was a correlation found with severe morbidity (aOR 1.322; 95% CI [1.003-1.743]; p = 0.048). A risk stratification tree showed that male newborns of >26 weeks with Hb of <15.5 g/dL (n = 703) were associated with a poor outcome at 24 months (OR 1.9; CI: [1.5-2.4] p < 0.01). CONCLUSIONS: Early low Hb levels are associated with major neonatal morbidities in VP singletons, but not with neurodevelopment outcomes at two years of age, except in male infants of >26 Weeks GA.

A correlation between Magnetic Resonance Spectroscopy (1-H MRS) and the neurodevelopment of two-year-olds born preterm in an EPIRMEX cohort study.

Background: Preterm infants are at risk of neurodevelopmental impairments. At present, proton magnetic resonance spectroscopy (1H-MRS) is currently used to evaluate brain metabolites in asphyxiated term infants. The purpose of this study was to identify in the preterm EPIRMEX cohort any correlations between (1H-MRS) metabolites ratio at term equivalent age (TEA) and neurodevelopmental outcomes at 2 years. Methods: Our study included EPIRMEX eligible patients who were very preterm infants (gestational age at birth ≤32 weeks) and who underwent a brain MRI at TEA and 1H-MRS using a monovoxel technique. The volumes of interest (VOI) were periventricular white matter posterior area and basal ganglia. The ratio of N Acetyl Aspartate (NAA) to Cho (Choline), NAA to Cr (creatine), Cho to Cr, and Lac (Lactate) to Cr were measured. Neurodevelopment was assessed at 24 months TEA with ASQ (Ages and Stages Questionnaire). Results: A total of 69 very preterm infants had a 1H-MRS at TEA. In white matter there was a significant correlation between a reduction in the NAA/Cho ratio and a total ASQ and/or abnormal communication score, and an increase in the Lac/Cr ratio and an abnormality of fine motor skills. In the gray nuclei there was a trend correlation between the reduction in the NAA/Cho ratio and sociability disorders; and the increase in the Lac/Cr ratio and an anomaly in problem-solving. Conclusions: Using NAA as a biomarker, the vulnerability of immature oligodendrocytes in preterm children at TEA was correlated to neurodevelopment at 2 years. Similarly, the presence of lactate at TEA was associated with abnormal neurodevelopment at 2 years in the preterm brain.

Implementation Outcomes and Challenges of Partnerships between Resource Parents and Parents with Sick Infants in Intensive Neonatal Care Units: A Scoping Review.

Parents with a sick child in a neonatal intensive care unit (NICU) usually experience stress, anxiety, and vulnerability. These precarious feelings can affect early parent-child interactions and have consequences for the child's neurodevelopment. Parents who have had a sick child in an NICU (veteran parents) can offer helpful interventions for these vulnerable families. This article is a scoping review of parental interventions used with the families of NICU infants, and an overview of French perspectives. Two independent reviewers studied the scientific literature published in English between 2001 to 2021 using Covidence software. The databases used were MEDLINE, ISI Web of Science, the Cochrane Database, and Google Scholar. Themes were identified from the articles' results using an open coding approach. The data are presented in a narrative format. Ten articles were included, and four major themes addressed: (1) description of activities, (2) recommendations, (3) impact, and (4) barriers (resulting from recruitment, training, remuneration, and organization). Activities were very diverse, and a step-by-step implementation was recommended by all authors. Peer-support interventions might be a potential resource for those anxious parents and improve their NICU experiences. These challenges are described by SOS Préma in France. This article brings together recent studies on partnership in the NICU. It is an innovative topic in neonatology with vast issues to explore.

Neonatal and Long-Term Prognosis of Monochorionic Diamniotic Pregnancies Complicated by Selective Growth Restriction.

BACKGROUND: There are few data concerning the neonatal and long-term prognosis of monochorionic biamniotic twin pregnancies (MCBA) complicated by selective intrauterine growth restriction (sIUGR). The aim of the study is to assess the neurological outcomes at two years of age of these newborns and compares these outcomes to those of newborns resulting from intrauterine growth restriction (IUGR) pregnancies. METHODS: The study focuses on a cross-sectional prospective cohort of patients treated between 2012 and 2019 in Marseille, France. The primary endpoint is the overall score of the Ages and Stages questionnaires (ASQ) at two years, which assesses the global neurodevelopment. The secondary endpoint is the assessment of neonatal morbi-mortality for both groups (composite endpoint). RESULTS: In total, 251 patients were included in the analysis: 67 in the sIUGR group and 184 in the IUGR group. There was no statistically significant difference in the overall ASQ score at two years but there was the finest motor skills impairment in the IUGR group. The areas most often impaired were communication and fine motor skills. There were no significant differences between the neonatal morbi-mortality of the two groups (adjusted OR = 0.95, p =0.9). CONCLUSIONS: Newborns from MCBA pregnancies with sIUGR appear to have similar overall neurological development to IUGR. Notably, IUGR seems to have the most moderate neurobehavioral disorder (fine motor) as a consequence of impaired antenatal brain development due to placenta insufficiency leading to chronic hypoxia.

Effect of Massage with Oil Balanced in Essential Fatty Acids on Development and Lipid Parameters in Very Premature Neonates: A Randomized, Controlled Study.

Background: Oil massage versus only massage can increase preterm newborn development, especially weight gain, via a supposed percutaneous absorption of oil lipids, but data are contradictory. Aims: Investigating whether massage with a vegetable oil balanced in essential fatty acids improves neonatal weight gain, and digestive autonomy as proxy for neuro-development outcomes. Methods: A prospective monocentric randomized study was conducted in very premature newborns who received massage with oil (isio4 10 mL/kg/day, n = 18) versus with no oil (n = 18) for five consecutive days (10-min session twice daily) at a corrected gestational age of 34−35 weeks. Anthropometrics and clinical characteristics were recorded. Plasma triglyceride and total cholesterol concentrations were analyzed with an enzymatic kit. The fatty acid composition (weight%, mg/mL) of total plasma lipids and of red blood cell (RBC) membrane was analyzed by gas chromatography. Results: Weight gain velocity at the end of massage period was 12.3 ± 1.4 g/kg/day with oil vs. 9.8 ± 1.4 g/kg/day with no oil (p = 0.1). Digestive autonomy, plasma lipid parameters, polyunsaturated fatty acids in plasma total lipids or in RBC were comparable. The no oil group displayed a higher RBC level in nervonic acid at discharge (4.3 ± 0.2 vs. 3.4 ± 0.2%; p = 0.025) and in C18:1n-9 plasmalogen species at the end of the massage period and at discharge (0.73 ± 0.06 vs. 0.48 ± 0.06; 0.92 ± 0.06 vs. 0.69 ± 0.06%; p < 0.01), two molecules that are involved in neurodevelopment. Conclusions: The use of isio4 oil did not provide additional benefits for the development of very premature newborns, neither changed lipid metabolism nor polyunsaturated fatty acid biological status, which did not corroborate the existence of a percutaneous route for oil lipid absorption. The reason for different levels of nervonic acid and plasmalogen in RBC remains to be explored.

Long Term Neurodevelopmental Outcomes after Sevoflurane Neonatal Exposure of Extremely Preterm Children: A Cross-Sectional Observationnal Study.

Sevoflurane, a volatile anesthetic, is used when extremely preterm neonates (EPT) undergo painful procedures. Currently, no existing studies analyze sevoflurane's long-term effects during the EPT's immediate neonatal period. Our primary objective was to compare the EPT's neurocognitive development regardless of any sevoflurane exposure prior to 45 weeks corrected gestational age (GA). We analyzed those live discharges, less than 28 weeks GA, who were either exposed, unexposed, and/or multiply exposed to sevoflurane before 45 weeks GA. All data were obtained from a cross-sectional multicenter study (GPQoL study, NCT01675726). Children, both exposed and non-exposed to sevoflurane, were sampled using a propensity-guided approach. Neurological examinations (Touwen), cognitive and executive functions (WISC IV, NEPSY, Rey figure), and assessments when the children were between 7 and 10 years old, were correlated to their neonatal sevoflurane exposure. There were 139 children in the study. The mean gestational age was 26.2 weeks (±0.8) GA and the mean birth weight was 898 g (±173). The mean age of their evaluation was 8.47 years old (±0.70). Exposure to sevoflurane to the mean corrected age 27.10 (3.37) weeks GA had a significant correlation with cerebral palsy (adjusted odds ratio (aOR): 6.70 (CI 95%: 1.84-32.11)) and other major disorders (cerebral palsy and/or severe cognitive retardation) (aOR: 2.81 [95% CI: 1.13-7.35]). Our results demonstrate the possibility of long-term effects on EPT infants who had a sevoflurane exposure before 45 weeks corrected GA. However, these results will require further confirmation by randomized controlled trials.

Neurobehavioral Phenotype and Dysexecutive Syndrome of Preterm Children: Comorbidity or Trigger? An Update.

Premature birth is a worldwide public health priority. One in ten children is born before 37 weeks of gestational age and, in developed countries, survival rates without major neonatal morbidity are increasing. Although severe sequelae associated with these births have decreased, their neurobehavioral difficulties, often associated in multiple fields, remain stable but still widespread. These neurobehavioral difficulties hamper the normal development of academic achievements and societal integration and intensify the children's needs for rehabilitation during their preschool and academic years. Severe sequelae increase when gestational age decreases. This is even truer if the socio-cultural background is impeded by low income, education and language skills as compared with defined averages. However, moderate and/or minor neurocognitive and/or behavioral difficulties are almost identical for a moderate or a late preterm birth. Obtaining a better clinical description of neurobehavioral characteristics of those pretermly born, once they reach preschool age, is essential to detect behavioral issues as well as early specific cognitive difficulties (working memory, planning, inhibition, language expression and reception, attention and fine motor skills, etc.). Such information would provide a better understanding of the executive functions' role in brain connectivity, neurodevelopment and neuroanatomical correlation with premature encephalopathy.

Selective intrauterine growth restriction of monochorionic diamniotic twin pregnancies: What is the neonatal prognosis?

OBJECTIVE: This study compares the neonatal morbidity and mortality of the smallest twins of monochorionic diamniotic (MCDA) pregnancies complicated with selective intrauterine growth restriction (sIUGR) with newborns from singleton pregnancies with intrauterine growth restriction (IUGR). METHODS: We conducted a retrospective cohort study of patients managed at the prenatal diagnosis center in a single tertiary care hospital between 2012 and 2019. MCDA twin pregnancies complicated with sIUGR (sIUGR group) were compared with singleton pregnancies with IUGR (IUGR group). The primary outcome was the comparison in neonatal morbidity and mortality between the two groups. RESULTS: The analysis included 251 patients: 67 in the sIUGR group and 184 in the IUGR group. The two groups were comparable in gestational age and birth weight (p > 0.05). Multivariate analysis controlling for factors that may influence neonatal status showed no significant difference between the two groups in any of the neonatal morbidity criteria or the composite morbidity-mortality endpoint (adjusted OR = 0.946 [95% CI = 0.317-2.827]; p = 0.921). CONCLUSION: Despite supposedly different pathophysiological mechanisms, neonates from MCDA pregnancies complicated with sIUGR and those from singleton pregnancies with IUGR appear to have identical neonatal morbidity and mortality .

Influence of intrapartum maternal fluids on weight loss in breastfed newborns.

OBJECTIVE: The main purpose of our study has been to establish a link between the administration of intravenous fluids during Labor and the weight loss experienced by infants during hospitalization. METHODS: We conducted a retrospective observational study using a descriptive and comparative method. We studied 150 records of patients who gave birth at term (low-risk pregnancy) of a single healthy new born with breastfeeding in a university hospital center between 1 January 2016 and 31 July 2016. Maternal, obstetrical and neonatal characteristics were registered to determine the influence of vascular filling by univariate and multivariate analysis and identified factors that may lead to increase neonatal weight loss. RESULTS: One hundred and fifty mother-child couples were studied. Newborns whom mothers received at least 1500 mL of solute during Labor lose significantly more weight until the third day of life (p < .001) compared to women who received less than 1500 mL, also observed for neonatal weight loss greater than 8% (p = .043). In addition, the obstetrical factors most significantly associated with an increase in the volume of solute injected were the duration of Labor (p < .001), the administration of oxytocin (p < .001), epidural analgesia (p = .01) and emergency cesarean section during Labor (p < .001). CONCLUSION: We found a link between vascular volume injected during Labor and increased risk of neonatal weight loss. Taking this factor into account when monitoring Labor in the birth room is essential to prevent and adapt neonatal management in the event of excessive weight loss. Influence of intrapartum maternal fluids on weight loss in breastfed newborns.

Predictive value of brain MRI at term-equivalent age in extremely preterm children on neurodevelopmental outcome at school-age.

This study's objective was to correlate the abnormalities in brain MRIs performed at corrected-term age for minor or moderate neurocognitive disorders in children school-age born extremely premature (EPT) and without serious sequelae such as autism, cerebral palsy, mental impairment. Data were issued from a cross-sectional multicenter study (GP-Qol study, number NCT01675726). Clinical examination and psychometric assessments were performed when the children were between 7 and 10 years old during a day-long evaluation. Term-equivalent age brain MRIs on EPT were analyzed with a standardized scoring system. There were 114 children included in the study. The mean age at the time of evaluation, was 8.47 years old (± 0.70). 59% of children with at least one cognitive impairment and 53% who had a dysexecutive disorder. Only ten EPT (8.7%) presented moderate to severe white and grey matter abnormalities. These moderate to severe grey matter abnormalities were associated with at least two abnormal executive functions [OR 3.08 (95% CI 1.04-8.79), p = 0.04] and language delay [OR 3.25 (95% CI 1.03-9.80), p = 0.04]. These results remained significant in the multivariate analysis. Moderate to severe ventricular dilatation abnormalities (15%, n = 17) were associated with ideomotor dyspraxia [OR 7.49 (95% CI 1.48-35.95), p = 0.02] and remained significant in multivariate analysis [OR 11.2 (95% CI 1.45-131.4), p = 0.02]. Biparietal corrected diameters were moderate abnormal in 20% of cases (n = 23) and were associated to visuo spatial integration delay [OR 4.13 (95% CI 1.23-13.63), p = 0.02]. Cerebral MRI at term-equivalent age with scoring system analysis can provide information on long-term neuropsychological outcomes at school-age in EPTs children having no severe disability.

Anterior Minithoracotomy vs. Transcatheter Closure of Patent Ductus Arteriosus in Very Preterm Infants.

Introduction: Patent ductus arteriosus (PDA) is common in preterm infants and contributes to morbidity and mortality. Several studies have shown the feasibility and safety of percutaneous PDA closure. Minimally invasive surgical ligation by anterior thoracotomy is an alternative, bedside technique for PDA closure in very low birth weight preterm infants. Our study aimed to compare short- and medium-term morbidity and mortality between anterior minithoracotomy and transcatheter PDA closure. Methods: From 2010 to 2020, 92 preterm infants <1,600 g underwent PDA closure in two centers: 44 surgical anterior minithoracotomies (center 1) and 48 transcatheter closures (center 2). Using a 1:1 propensity score match analysis, 22 patients in each group were included. The primary outcome was time to extubation after intervention. Results: Preoperative characteristics were similar in both groups after propensity matching (mean weight at procedure, 1,171 ± 183 g; p = 0.8). Mean time to extubation was similar: 10 ± 15 days in the surgical group vs. 9 ± 13 days in the transcatheter group (p = 0.9). Mean age at hospital discharge was 114 ± 29 days vs. 105 ± 19 days (p = 0.2). Two deaths occurred in the surgical group and one in the transcatheter group (p = 0.61). Five complications (pneumothorax n = 2, chylothorax n = 2, phrenic nerve injury n = 1) occurred in three patients after surgery. Three complications (chylothorax n = 1, endocarditis n = 1, renal vein thrombosis n = 1) occurred in two patients after percutaneous closure (p = 0.63). Conclusion: Equivalent efficiency and safety of surgical mini-invasive vs. transcatheter PDA closure in preterm infants <1,600 g are in favor of applying these alternative techniques according to centers' facilities and competences.

Cardio-Respiratory Events and Food Autonomy Responses to Early Uni-Modal Orofacial Stimulation in Very Premature Babies: A Randomized, Controlled Study.

Uni-modal orofacial stimulation (OFS) for preventing very preterm infants' oral disorders is highly controversial. Our study sought to demonstrate that OFS reduced cardio-respiratory events and improved food autonomy in a population of very preterm infants. Our study was randomized, controlled, prospective, and unicentric. The preterm included were born between 26-29 weeks gestational age (GA) with a corrected postnatal age <33 weeks GA. They were randomized into two groups: the experimental group underwent OFS, according to a protocol established, over 10 consecutive days, and the control group underwent no OFS. The primary outcome was the number of cardiorespiratory events: apnea-bradycardia (with or without desaturations) or number of isolated desaturations, which were evaluated at four separate times. Measurements occurred during the first, fourth and eighth independent feedings. Seventeen patients were included in the experimental group and 18 in the control group. The number of cardiorespiratory events for all independent feeding times was significantly reduced in the OFS group (p = 0.003) with univariate analysis, but not with multivariable analysis. The quantity of milk ingested during the first autonomous feeding was higher in the experimental group. The acquisition of food autonomy and the duration of hospitalization were similar in the two groups. While our study does not affirm that an early unimodal OFS improves premature infants' cardiorespiratory evolution and/or the acquisition of food autonomy, it does indicate an improved food efficiency during their first autonomous feedings.

The Neurobehavioral Phenotype of School-Aged, Very Prematurely Born Children with No Serious Neurological Sequelae: A Quality of Life Predictor.

School-aged extremely preterm (EPT) children have multiple specific neurocognitive/behavioral disorders that are often associated with other disorders; this manifests a true neurobehavioral "phenotype" of prematurity. To determine a profile of cognitive/behavioral impairments in a population of school-aged EPT children (7-10 years-old) without major disabilities, a cross-sectional study was conducted in five medical centers. An algorithm distributed the study population according to four WISC-IV subtests, five NEPSY-2 subtests, and two variables of figure of Rey. The behavior (SDQ), anxiety (Spielberg STAI-C), and generic QoL (Kidscreen 10 and VSP-A) were also evaluated. The study included 231 school-aged EPT children. Three neurobehavioral "phenotypes" were defined according to their severity: 1 = moderately, 2 = minor, and 3 = unimpaired. In all the profiles, the working memory, perceptual reasoning, as well as mental flexibility, were close to or below average, and their emotional behavior was always troubled. Self-esteem and school-work were the most impacted QoL areas. The unimpaired neurobehavior exhibited emotional behavioral impairment and executive dysfunction. The profile analysis defined distinct outcome groups and provided an informative means of identifying factors related to developmental outcomes. The QoL deterioration is determined by the severity of the three neurobehavioral "phenotypes", which is defined as well as by dysexecutive and/or behavioral disorders.

Severe maternal morbidity in preterm cesarean delivery: A systematic review and meta-analysis.

OBJECTIVE: More than half of extremely preterm infants are delivered by cesarean section. Few data are available about severe maternal morbidity (SMM) of these extremely preterm cesarean. The objective was to determine whether gestational age under 26 weeks of gestation (weeks) was associated with an increased risk of SMM compared with gestational age between 26 and 34 weeks in women having a cesarean delivery. MATERIAL AND METHODS: We searched MEDLINE, ISI Web of Science, the Cochrane Database, PROSPERO, and ClinicalTrials.gov on January 31, 2020. The search strategy clustered terms describing SMM and preterm cesarean delivery. No restrictions on language, publication status, and study design were applied. Abstracts were included if there was sufficient information to assess study quality. The authors of all identified studies were contacted to request for aggregated data. Relative risks (RR) were calculated using the inverse variance method. The primary outcome was SMM as defined in each study. We analyzed data on preterm cesarean deliveries between 22 and 34 weeks. The protocol was registered in PROSPERO (registration: CRD42019128644). RESULTS: Six studies involving 45,572 women (3,440 delivering < 26 weeks; 42,132 delivering between 26 and 34 weeks) were included. SMM occurred in 607 women (17.6 %) < 26 weeks and 4,483 women (10.6 %) between 26 and 34 weeks. Gestational age < 26 weeks was associated with an increased risk of SMM (RR, 1.65; 95 % CI [Confidence Interval], 1.52-1.78; I2 = 40 %). Gestational age < 26 weeks remained associated with SMM in the subgroup analyses depending on the type of the study (prospective or retrospective), country of the study (European or non-European), and high quality of the study. A sensitivity analysis showed that gestational age < 25 weeks was also associated with SMM in preterm cesarean delivery (RR, 1.66; 95 % CI, 1.50-1.83; I2 = 3%). CONCLUSIONS: Gestational age < 26 weeks was associated with an increased risk of SMM in women having a preterm cesarean delivery. Obstetricians and neonatologists should be aware of the increased risk of SMM in cesarean.