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.

Maternal consumption of quinine-containing sodas may induce G6PD crises in breastfed children.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect often presenting with neonatal jaundice and/or hemolytic anemia. G6PD hemolytic events are linked with exposure to a pro-oxidant agent. We here report three cases of initial G6PD crises in breastfed children secondary to maternal consumption of a tonic drink which contains quinine. Quinine was found in breast milk of one of the mothers after she consumed tonic water. CONCLUSION: The amount of quinine that is transmitted through breast milk appears to be sufficient to induce G6PD crises in breastfed children. We hence recommend that consumption of quinine-containing sodas during breastfeeding should be avoided in populations with a high prevalence of G6PD deficiency. What is Known: • G6PD hemolytic events are linked with exposure to a pro-oxidant agent. • Ingestion of fava beans by a mother who was breastfeeding has been reported to induce a neonatal G6PD crisis. What is New: • Maternal consumption of tonic drink which contains quinine appears to be sufficient to induce G6PD crises in breastfed children. • Maternal consumption of quinine-containing sodas during breastfeeding should be avoided in populations with a high prevalence of G6PD deficiency.

Comparative phenotypic analysis of "Clostridium neonatale" and Clostridium butyricum isolates from neonates.

"Clostridium neonatale" was recently described as a new species within the Cluster I of the Clostridium genus sensu stricto. In this study, we characterized "C. neonatale" isolates (n = 42) and compared their phenotypic properties with those of Clostridium butyricum (n = 26), a close related species. Strains isolated from fecal samples of healthy neonates were tested for different phenotypic characteristics. Compared to C. butyricum, "C. neonatale" showed a significant higher surface hydrophobicity (p = 0.0047), exopolysaccharide production (p = 0.0069), aero-tolerance (p = 0.0222) and viability at 30 °C (p = 0.0006). A lower swimming ability (p = 0.0146) and tolerance against bile (0.3%) (p = 0.0494), acid (pH 4.5) (p < 0.0001), osmolarity (NaCl 5%, p = 0.0188) and temperature at 50 °C (p = 0.0013) characterized "C. neonatale" strains. Our results showed that "C. neonatale" behaves very differently from C. butyricum and suggests specific responses to environmental changes. Besides it is the first study on clinical isolates for these two anaerobic members of the newborns' gut microbiota and broadens our knowledge about their phenotypic traits.

Association of severe placental inflammation with death prior to discharge and cerebral palsy in preterm infants.

OBJECTIVE: The objective of our study was to identify placental patterns associated with death before discharge or cerebral palsy in a large cohort of preterm infants with a high follow-up rate at 2 years of corrected age. DESIGN: Population-based monocentric study. SETTINGS: Monocentric study in the maternity unit of the University Hospital of Angers, France between 24+0 and 33+6  weeks of gestation, between January 2008 and December 2011. POPULATION: All singleton infants born alive with a placental examination were eligible. METHODS: Clinical data (obstetric and neonatal) were collected prospectively through the LIFT cohort. Placental data were collected retrospectively from medical records. The main outcome measure was death before discharge or cerebral palsy. RESULTS: We did not find any significant association between severe inflammatory lesions on the placenta and death [odds ratio (OR) 1.49; 95% CI 0.55-4.01; P = 0.43] or cerebral palsy (OR 1.41; 95% CI 0.43-4.62; P = 0.57). This lack of significant association persisted even after adjustment (aOR 0.9; 95% CI 0.20-2.30; P = 0.54; aOR 0.98; 95% CI 0.27-3.58; P = 0.97). CONCLUSION: Our results do not provide evidence for a significant association between severe inflammatory placental lesions and either death before discharge or cerebral palsy at 2 years of corrected age in preterm infants born at <34 weeks of gestational age. Further studies remain necessary to confirm this result. TWEETABLE ABSTRACT: We found no significant association between inflammatory placental lesions and death or cerebral palsy.

A new procalcitonin cord-based algorithm in early-onset neonatal infection: for a change of paradigm.

Diagnostic of early-onset neonatal infection (EONI) remains an emergency. Recent studies underline the potential benefit of using Procalcitonin (PCT) in early diagnosis of bacterial infections in neonates. The aim of this study was to evaluate the diagnostic value of an umbilical blood cord PCT based algorithm in newborns suspected of EONI. The diagnostic value of the PCT based algorithm was compared to the French one currently in use by analyzing an 18-months database of newborns suspected of EONI in University Hospital of Nantes from March 2011 to September 2012. Among the 2,408 (40.8 %) newborns suspected of infection during this period, 2,366 were included in the study. The incidence of EONI was 3.4‰ (n = 20). There was no significant difference between the sensibilities of the PCT based algorithm and the current algorithm (90 %, respectively, 95%CI 76.9-100 versus 85.4-100; p = 0.90) and between their specificities (respectively 91.7 % (90.6-92.8) versus 87.4 % (86-88.7); p = 0.25). The antibiotic treatment rate would be significantly reduced with the PCT based algorithm [211 i.e. 8.9 % (7.8-10) versus 314 i.e. 13.3 % (11.9-14.7) in the current algorithm; p < 0.005] and less biological analysis would be performed [301 i.e. 12.7 % (11.4-14) versus 937 i.e. 39.6 % (37.6-41.6); p < 0.005]. Blood cord PCT seems to be a new and efficient marker to guide neonatologists taking care of newborns suspected of EONI. The PCT algorithm seems to be a safe alternative in diagnosis of EONI, allowing detection of EONI significantly as well as the current algorithm, without resulting in a substantially higher number of missed infections. These results have to be confirmed by a multicentric validation study.

Respiratory morbidity of preterm infants of less than 33 weeks gestation without bronchopulmonary dysplasia: a 12-month follow-up of the CASTOR study cohort.

The aim of this study was to describe the incidence and risk factors for respiratory morbidity during the 12-month period following the first respiratory syncytial virus (RSV) season in 242 preterm infants [<33 weeks gestational age (GA)] without bronchopulmonary dysplasia and 201 full-term infants (39-41 weeks GA) from the French CASTOR study cohort. Preterm infants had increased respiratory morbidity during the follow-up period compared to full-terms; they were more likely to have wheezing (21% vs. 11%, P = 0·007) and recurrent wheezing episodes (4% vs. 1%, P = 0·049). The 17 infants (14 preterms, three full-terms) who had been hospitalized for RSV-confirmed bronchiolitis during their first RSV season had significantly more wheezing episodes during the follow-up period than subjects who had not been hospitalized for RSV-confirmed bronchiolitis (odds ratio 4·72, 95% confidence interval 1·71-13·08, P = 0·003). Male gender, birth weight <3330 g and hospitalization for RSV bronchiolitis during the infant's first RSV season were independent risk factors for the development of wheezing episodes during the subsequent 12-month follow-up period.

Lower risk of atopic dermatitis among infants born extremely preterm compared with higher gestational age.

BACKGROUND: It is not yet known whether the risk of developing atopic dermatitis (AD) is influenced by preterm birth. Moreover, AD risk has not been assessed in a large sample of extremely preterm infants (< 29 weeks' gestation). OBJECTIVES: To determine whether the risk of AD is influenced by preterm birth. METHODS: We investigated the relationship between gestational age (GA) and AD using data from two independent population-based cohorts, including a total of 2329 preterm infants, of whom 479 were born extremely preterm. RESULTS: There was a lower percentage of children with AD in the extremely preterm group compared with those born at a greater GA (Epipage cohort, 2-year outcome: 13·3% for 24-28 weeks, 17·6% for 29-32 weeks, 21·8% for 33-34 weeks, P = 0·02; LIFT cohort, 5-year outcome: 11% for 24-28 weeks, 21·5% for 29-32 weeks, 19·6% for 33-34 weeks, P = 0·11). After adjusting for confounding variables, a lower GA (< 29 weeks) was significantly associated with decreased risk of AD in the Epipage cohort [adjusted odds ratio (aOR) 0·57, 95% confidence interval (CI) 0·37-0·87; P = 0·009] and the LIFT cohort (aOR 0·41, 95% CI 0·18-0·90; P = 0·03). CONCLUSIONS: Very low GA (< 29 weeks) was associated with a lower risk of AD compared with higher GA (29-34 weeks) and full-term birth.

Hospitalizations for respiratory syncytial virus bronchiolitis in preterm infants at <33 weeks gestation without bronchopulmonary dysplasia: the CASTOR study.

This study was conducted during the 2008-2009 respiratory syncytial virus (RSV) season in France to compare hospitalization rates for bronchiolitis (RSV-confirmed and all types) between very preterm infants (<33 weeks' gestational age, WGA) without bronchopulmonary dysplasia and full-term infants (39-41 WGA) matched for date of birth, gender and birth location, and to evaluate the country-specific risk factors for bronchiolitis hospitalization. Data on hospitalizations were collected both retrospectively and prospectively for 498 matched infants (249 per group) aged <6 months at the beginning of the RSV season. Compared to full-term infants, preterm infants had a fourfold [95% confidence interval (CI) 1·36-11·80] and a sevenfold (95% CI 2·79-17·57) higher risk of being hospitalized for bronchiolitis, RSV-confirmed and all types, respectively. Prematurity was the only factor that significantly increased the risk of being hospitalized for bronchiolitis. The risk of multiple hospitalizations for bronchiolitis in the same infant significantly increased with male gender and the presence of siblings aged ⩾2 years.

[Medical termination of pregnancy for isolated intrauterine growth retardation beyond 24 weeks and more than 450g]. / Interruption médicale de grossesse pour retard de croissance intra-utérin isolé au-delà de 24 SA et de 450g.

INTRODUCTION: Fetal growth restriction (FGR) is an obstetric complication responsible for increased perinatal morbidity and mortality. In some severe and early FGR situations, termination of pregnancy (TOP) may be considered. The main objective of our study was to describe the population of fetuses for whom a TOP was performed for isolated FGR beyond 24 days' gestation and for a birth weight>450g and to analyze the immediate outcome, at 2 and 5 years, of term- and weight-matched neonates born in a context of severe FGR after 24 weeks' gestation and over 450g. MATERIAL AND METHODS: We conducted an observational, descriptive, retrospective, uni-centric study between 2008 and 2018. The primary endpoint was survival at maternity discharge, 2 years and 5 years in these children. Secondary endpoints were assessment of immediate and longer-term postnatal morbidity. Twenty-five patients (36%) were selected for the study with a fetus weight>450g and term>24 weeks. Each fetus with an TOP was matched (on gestational age and weight) with two live-born children from the perinatal network cohort to assess immediate discharge outcome, and then at 2 and 5 years. RESULTS: The mortality rate was 24%. In neonatal management, for 67% (n=17) of the newborns the evolution was complicated by death or at least two sequelae (bronchopulmonary dysplasia, hyaline membrane disease stage≥2, intraventricular of grade 3 and 4, ulcerative colitis requiring surgery, retinopathy of prematurity stage 2 and more) at discharge. In 32% (n=8) of cases, there was at least one sequela at discharge. Regardless of gestational age at birth, development at 2 years was normal for 48% (n=11/23) of them and abnormal for 22% (n=5) and development at 5 years was normal for 56% (n=9/16) of them and abnormal for 19% (n=5). CONCLUSION: An ultrasound evaluation in a reference center as well as additional information by the obstetrician and neonatologist ensures the most appropriate informed involvement of the couple in the medical decisions before and after birth.

Identification of newborns at risk of early-onset neonatal infection: New French guidelines and practices at Nantes University Hospital.

New French guidelines in 2017 aimed to improve the identification of newborns at risk of early-onset neonatal infection (EONI). Identification is based on perinatal risk factors, management of perinatal antibiotic prophylaxis, and standardized clinical assessment. We conducted a retrospective cross-study at the University Hospital of Nantes. The main objective was to assess implementation of the French guidelines. Of 1240 births included, 40% (501) required perinatal antibiotic prophylaxis (adequate in 67.3%) and 306 (24.7%) needed a standardized clinical assessment (performed in 69.2%). Only two newborns (0.16%) included in the study received neonatal antibiotic therapy. On the basis of the assessment conducted in our maternity ward, implementation of the recommendations seems to be effective.

Antenatal phosphodiesterase 4 inhibition restores postnatal growth and pulmonary development in a model of chorioamnionitis in rabbits.

Chorioamnionitis is implicated in the pathophysiology of bronchopulmonary disease, and the associated inflammatory response is responsible for adverse effects on alveolar development. The aim of this work was to analyze the effects of a phosphodiesterase 4 (PDE4)-selective inhibitor, rolipram (a modulator of the inflammatory response), in an experimental model of chorioamnionitis on pulmonary development and on the processes of infection and inflammation. Rabbit mothers were assigned to four groups: 1) saline serum inoculation (controls); 2) Escherichia coli intrauterine inoculation (C+); 3) rolipram infusion (R+); and 4) E. coli inoculation + rolipram infusion (C+R+). High rates of morbility and mortality were noticed in mothers and pups (5 of 13 pregnant rabbits in groups with rolipram). Alveolar development, inflammation, and infection were analyzed in pups at day 0 and day 5. At day 0, in the context of chorioamnionitis, rolipram significantly decreased birth weight (p < 0.01) relative to that of controls (p < 0.05). At day 5, weight normalized in group C+R+ but not in group C+ relative to controls (p < 0.001); moreover, alveolar airspace volume was preserved in group C+R+ but not in group C+ (p < 0.05). Interstitial volume decreased in group C+ versus controls (p < 0.05) but was preserved in group C+R+. Specific alveolar area was not significantly modified by rolipram. No significant difference was found concerning bronchoalveolar lavage cellularity, and all blood cultures remained sterile. In this model of impaired alveologenesis, rolipram significantly preserved specific alveolar density. However, PDE4 inhibition induced antenatal fetal demise and growth retardation.

Umbilical cord blood procalcitonin as a risk factor for mortality in very premature infants.

Fetal inflammatory response syndrome is implicated as a cause of fetal or neonatal injury. We analyzed the relationship between the procalcitonin umbilical cord blood level and neonatal outcome. A total of 237 preterms born in a level III perinatal medicine unit of a French university hospital were enrolled in a prospective observational study. Measurement of the procalcitonin umbilical cord blood level was performed at birth. After hospitalization, surviving infants were enrolled in the regional follow-up program. Outcome data were recorded on standardized questionnaires. The main outcome measures were neonatal mortality and impaired functional outcome at 2 years of corrected age. The terciles of procalcitonin levels were calculated. Preterm infants of the third tercile were defined as infants with elevated procalcitonin. Among the 237 infants, 13 (5.5%) died during the neonatal period, 20 (8.4%) were lost to follow-up, and 31 (13.1%) were classified as having an impaired functional outcome. After adjustment, elevated cord blood procalcitonin (>0.33 ng/ml) was significantly associated with an increase in mortality (adjusted odds ratio [aOR] = 8.3 [1.4-48]; p = 0.018), but not with the 2-year impaired functional outcome (aOR = 1.0 [0.4-2.5]; p = 0.93). Elevated umbilical blood cord procalcitonin concentration is an independent risk factor of mortality in preterm infants at less than 33 weeks' gestation.

Father newborn skin-to-skin wheelchair transfer from delivery room to neonatal care unit: Possible change in practices.

OBJECTIVE: To evaluate the transfer of newborns from the delivery room to the neonatal care unit with their fathers on wheelchairs in terms of the safety of the procedure and paternal anxiety. METHODS: A prospective observational single-center before-and-after pilot study was conducted from February to May 2018 at the University Maternity Hospital of Nantes. Safe transfer was judged on the basis of episodes of hypothermia or hypoglycemia. Paternal anxiety was assessed with the State-Trait Anxiety Inventory (STAI) scale after newborn transfer. RESULTS: Overall, 70 preterm newborns were enrolled, 44 were carried in wheelchairs in the father's arms (target group) and 26 were transferred in an incubator (control group). After adjusting for gestational age and birthweight, there were no statistically significantly differences between the target and the control group in the rates of hypothermia (43.9% vs 30.8%, p = 0,59) and hypoglycemia (9.52% vs 19.23%, p = 0,19). The STAI scale score was not significantly different between groups after incubator transfer or wheelchair transfer, at 35 ± 8.2 and 38 ± 10.2, respectively (p = 0.07). CONCLUSION: Transferring a newborn to the neonatal care unit via wheelchair with the father is a safe alternative to incubator transfer.

The role of nutrition in non-alcoholic fatty liver disease treatment in obese children.

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease that occurs mostly in the context of insulin resistance and obesity. It has rapidly evolved into the most common cause of liver disease among children. The incidence is high in obese children and a greater risk of disease progression is associated with severe obesity, highlighting the role of nutrition. To date, there is no consensus on NAFLD management. This is a narrative review of clinical studies on the potential benefit of nutritional interventions, including lifestyle modifications, vitamins, docosahexaenoic acid, and probiotics in children with NAFLD. The Comité de nutrition de la Société Française de Pédiatrie (CN-SFP) emphasizes the effect of limiting added sugar intake, i.e., fructose or sucrose-containing beverages, and promoting physical activity in the care of NAFLD.

"Baby-led weaning" - Progress in infant feeding or risky trend?

Baby-led weaning (BLW), proposed as a new form of complementary feeding, has emerged as a real trend phenomenon in the media. Infants are seated at the family table from the age of 6 months, facing the foods they grab and bring to their mouth: they decide which foods they want to eat and what amount. The consumption of mashed foods and the use of a spoon are totally discouraged. BLW is increasingly used in nurseries and centers of young children. A bibliographic search carried out between 2000 and 2021 found 423 articles, of which 38 were selected. The clinical studies selected are 11 cross-sectional observational studies and two randomized controlled studies. BLW promotes breastfeeding, the early introduction of morsels, the respect of the child's appetite, the use of unprocessed foods, and the choice of "homemade" and friendliness. These benefits can nonetheless be reached with usual complementary feeding (SCF), according to current recommendations. Other benefits are claimed without scientific evidence such as easier achievement of dietary complementary feeding and an optimal growth with prevention of excess weight gain. BLW has some obvious downsides. The infant may not get enough energy, iron, zinc, vitamins, and other nutrients, or too much protein, saturated fat, salt, or sugar. The risk of choking, which must be distinguished from the physiological gagging reflex, has not been ruled out by scientific studies. Currently, the Nutrition Committee of the French Pediatric Society considers that the data published to date in terms of benefits and risks of BLW do not lend themselves to advice for this practice in preference over SCF carried out according to current recommendations.

Umbilical cord blood procalcitonin level in early neonatal infections: a 4-year university hospital cohort study.

This article describes a study of procalcitonin (PCT) measured in cord blood as a discriminating marker of early-onset neonatal infection. This was a monocenter retrospective study with prospective collection of data including all babies born during the study period. Those presenting infection risk factors had PCT measurement. Three groups were defined: certainly infected, probably infected, and non-infected. A total of 12,485 newborns were included, 2151 had PCT measurement, and 26 were infected. Receiver operating curves of PCT determined 0.6 ng/ml as the best cut-off, with an area under the curve of 0.96 (CI 95% 0.95-0.98). Sensitivity, specificity, positive and negative predictive value and positive and negative likelihood ratios were 0.92 (range, 0.75-0.98), 0.97 (0.96-0.98), 0.28 (0.20-0.36), 0.99 (0.99-0.99), 32 (24-41) and 0.08 (0.02-0.3), respectively. Post-test probabilities were 28% (23-33) if the test was positive, and less than 0.001% (0-1.10(-5)) if the test was negative. Gestational age between 28 and 32 weeks (OR 4.4; range, 1.2-16.2) and pH at birth < 7.10 (OR 2.9; 1.1-7.4) were other independent factors of increasing PCT (p < 0.05). PCT measured in umbilical cord blood is reliable to detect early infected and non-infected newborns.

Epidemiology of invasive early-onset neonatal infection in a French administrative district: A 10-year population-based study.

BACKGROUND: In light of the pending update of the French guidelines for the management of neonatal infections, knowing the current epidemiology of early-onset neonatal infection (EONI) is essential. OBJECTIVES: The aim of this study was to assess the current epidemiology of a French administrative district population of proven EONI, including umbilical cord blood procalcitonin levels. METHODS: We conducted a retrospective population-based study in the Nantes metropolitan area. We included all infants treated for proven EONI in the maternity, neonatology, and intensive care wards between 1 January 2006 and 31 December 2015 in the Nantes University Hospital. RESULTS: Among the 140,502 children born during the study period, 61 cases of EONI were documented. The overall incidence of confirmed EONI was 0.43/1000 live births, with 0.23/1000 GBS (group B streptococcus) infections and 0.08/1000 Escherichia coli infections. The majority of infected newborns were full-term or late-preterm infants (67% were≥34 weeks of gestation), 88% had symptoms of EONI in the first 24h of life, most of which were respiratory. The mortality rate was 8% (in premature infants). Available in 51% of the population, the cord blood PCT value could contribute to an earlier diagnostic screening in 10% of cases but with a very low sensitivity. CONCLUSIONS: The incidence of confirmed EONI is low in this French district. The diagnostic value of PCT umbilical blood cord should be assessed based on further studies before confirming its value. We suggest that a national registry of these rare but serious cases of EONI could contribute to monitoring the epidemiological progression as well as to optimizing our diagnostic and therapeutic strategies.

Variations in patterns of care across neonatal units and their associations with outcomes in very preterm infants: the French EPIPAGE-2 cohort study.

OBJECTIVES: To describe patterns of care for very preterm (VP) babies across neonatal intensive care units (NICUs) and associations with outcomes. DESIGN: Prospective cohort study, EPIPAGE-2. SETTING: France, 2011. PARTICIPANTS: 53 (NICUs); 2135 VP neonates born at 27 to 31 weeks. OUTCOME MEASURES: Clusters of units, defined by the association of practices in five neonatal care domains - respiratory, cardiovascular, nutrition, pain management and neurodevelopmental care. Mortality at 2 years corrected age (CA) or severe/moderate neuro-motor or sensory disabilities and proportion of children with scores below threshold on the neurodevelopmental Ages and Stages Questionnaire (ASQ). METHODS: Hierarchical cluster analysis to identify clusters of units. Comparison of outcomes between clusters, after adjustment for potential cofounders. RESULTS: Three clusters were identified: Cluster 1 with higher proportions of neonates free of mechanical ventilation at 24 hours of life, receiving early enteral feeding, and neurodevelopmental care practices (26 units; n=1118 babies); Cluster 2 with higher levels of patent ductus arteriosus and pain screening (11 units; n=398 babies); Cluster 3 with higher use of respiratory, cardiovascular and pain treatments (16 units; n=619 babies). No difference was observed between clusters for the baseline maternal and babies' characteristics. No differences in outcomes were observed between Clusters 1 and 3. Compared with Cluster 1, mortality at 2 years CA or severe/moderate neuro-motor or sensory disabilities was lower in Cluster 2 (adjusted OR 0.46, 95% CI 0.25 to 0.84) but with higher proportion of children with an ASQ below threshold (adjusted OR 1.49, 95% CI 1.07 to 2.08). CONCLUSION: In French NICUs, care practices for VP babies were non-randomly associated. Differences between clusters were poorly explained by unit or population differences, but were associated with mortality and development at 2 years. Better understanding these variations may help to improve outcomes for VPT babies, as it is likely that some of these discrepancies are unwarranted.

Efficacy and safety of hydrolyzed rice-protein formulas for the treatment of cow's milk protein allergy.

Foods for special medical purposes (FSMPs) with a protein fraction made of hydrolyzed rice protein (HRPs) have been on the market in Europe since the 2000s for the treatment of cow's milk protein allergy (CMPA). HRP formulas (HRPFs) are proposed as a plant-based alternative to cow's milk protein-based extensively hydrolyzed formulas (CMP-eHF) beside the soy protein formulas whose use in CMPA is controversial. HRPFs do not contain phytoestrogens and are derived from non-genetically modified rice. HRPFs are strictly plant-based apart from the addition of vitamin D3 (cholecalciferol). As the amino acid content of rice proteins differs from that of human milk proteins, the protein quality of these formulas is improved by supplementation with free lysine, threonine, and tryptophan. The consumption of HRPFs has risen: for example, in France HRPFs account for 4.9% in volume of all formulas for children aged 0-3 years. Several studies have shown the adequacy of HRPFs in treating CMPA. They ensure satisfactory growth from the 1st weeks of life for infants and toddlers, both in healthy children and in those with CMPA. HRPFs can be used to treat children with CMPA either straightaway or in second intention in cases of poor tolerance to CMP-eHF for organoleptic reasons or for lack of efficacy. In France, the cost of HRPFs is close to that of regular infant or follow-on formulas.