Optimal Delivery Management for the Prevention of Early Neonatal SARS-CoV-2 Infection: Systematic Review and Meta-analysis.

OBJECTIVE: Delivery management interventions (DMIs) were recommended to prevent delivery-associated transmission of maternal SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) to infants without evidence of effect on early neonatal SARS-CoV-2 infection (ENI) and neonatal death <28 days of life (ND). This systematic review describes different DMI combinations and the frequency of ENI and ND. STUDY DESIGN: Individual patient data were collected from articles published from January 1, 2020 to December 31, 2021 from Cochrane review databases, Medline, and Google Scholar. Article inclusion criteria were: documented maternal SARS-CoV-2 polymerase chain reaction (PCR)-positive status 10 days before delivery or symptomatic at delivery with a positive test within 48 hours, known delivery method, and known infant SARS-CoV-2 PCR result. Primary outcomes were ENI (positive PCR at 12 hours to 10 days) and ND. All characteristics were pooled using the DerSimonian-Laird inverse variance method. Primary outcome analyses were performed using logit transformation and random effect. Pooled results were expressed as percentages (95% confidence intervals). Continuity correction was applied for all pooled results if any included study has 0 event. RESULTS: A total of 11,075 publications were screened. 117 publications representing 244 infants and 230 mothers were included. All publications were case reports. ENI and ND were reported in 23.4% (18.2-29.18) and 2.1% (0.67-4.72) of cases, respectively. Among cases with available information, DMIs were reported for physical environment (85-100%), delivery-specific interventions (47-100%), and infant care practices (80-100%). No significant comparisons could be performed between different DMI combinations due to small sample size. CONCLUSION: The evidence supporting any DMI in SARS-CoV-2-infected mothers to prevent ENI or ND is extremely limited. Limitations of this meta-analysis include high risk of bias, small sample size, and large confidence intervals. This identifies the need for multinational database generation and specific studies designed to provide evidence of DMI guidelines best suited to prevent transmission from mother to neonate. KEY POINTS: · In this review we analyzed 2 years of maternal SARS-CoV-2 published cases.. · We assessed association of delivery management interventions with infant SARS-CoV-2 infection.. · We found no evidence supporting any DMI for that purpose..

Impact of corticosteroid exposure on preterm labor in neonates eventually born at term.

OBJECTIVE: To evaluate the impact of antenatal corticosteroid therapy (ACS) on birth outcomes in term infants exposed during pregnancy. STUDY DESIGN: Exposed newborns were compared with non-exposed controls in a 1 to 2 design. Multivariate analysis was used to assess the effect of ACS exposure on neonatal outcomes. RESULT: 408 newborns were included (136 exposed to ACS, 272 non-exposed). Mean ± SD head circumference (HC) was 33.7 ± 1.4 vs 34.3 ± 1.6 cm, p = 0.001 in exposed vs controls; birth weight was 3.1 ± 0.4 vs 3.3 ± 0.4 kg, p = 0.0001; and birth height was 47.9 ± 2.1 vs. 49.1 ± 2.0 cm, p < 0.0001. Hypocalcemia (4.4 vs 0.7%, p = 0.019) and feeding difficulties (5.1 vs 1.5%, p = 0.047) were significantly more common in exposed newborns. Multivariate analysis for HC showed a significant independent association with ACS exposure (ß = -0.5, p = 0.009). CONCLUSION: Term newborns exposed to ACS have lower birth HC and higher risk of neonatal complications. CLINICAL TRIAL REGISTRATION: NCT05640596.

Outcomes at 7 Years of Age of Former Very Preterm Neonates with Repeated Surfactant Treatment for Prolonged Respiratory Distress in the Neonatal Period.

This study aimed at evaluating the 7-year outcomes of 118 very preterm newborns (VPNs, gestational age = 26 ± 1.4 w) involved in a randomized controlled trial. They presented neonatal respiratory distress (RDS), requiring ventilation for 14 ± 2 days post-natal age (PNA). A repeated instillation of 200 mg/kg poractant alfa (SURF) did not improve early bronchopulmonary dysplasia, but the SURF infants needed less re-hospitalization than the controls for respiratory problems at 1- and 2-year PNA. There was no growth difference at 7.1 ± 0.3 years between 41 SURF infants and 36 controls (80% of the eligible children), and 7.9% SURF infants vs. 28.6% controls presented asthma (p = 0.021). The children underwent cognitive assessment (WISC IV) and pulmonary function testing (PFT), measuring their spirometry, lung volume, and airway resistance. The spirometry measures showed differences (p < 0.05) between the SURF infants and the controls (mean ± standard deviation (median z-score)) for FEV1 (L/s) (1.188 ± 0.690(-0.803) vs. 1.080 ± 0.243 (-1.446)); FEV1 after betamimetics (1.244 ± 0.183(-0.525) vs. 1.091 ± 0.20(-1.342)); FVC (L) (1.402 ± 0.217 (-0.406) vs. 1.265 ± 0.267 (-1.141)), and FVC after betamimetics (1.452 ± 0.237 (-0.241) vs. 1.279 ± 0.264 (-1.020)). PFT showed no differences in the volumes or airway resistance. The global IQ median (interquartile range) was 89 (82:99) vs. 89 (76:98), with 61% of the children >85 in both groups. Repeated surfactant treatment in VPNs presenting severe RDS led to the attenuation of early lung injuries, with an impact on long-term pulmonary sequelae, without differences in neurodevelopmental outcomes.

Cognitive Training for Visuospatial Processing in Children Aged 5½ to 6 Years Born Very Preterm With Working Memory Dysfunction: A Randomized Clinical Trial.

Importance: Compared with term-born peers, children born very preterm generally perform poorly in executive functions, particularly in working memory and inhibition. By taking advantage of neuroplasticity, computerized cognitive training of working memory in those children could improve visuospatial processing by boosting visual inhibition via working memory. Objective: To evaluate the long-term effect of cognitive working memory training on visuospatial processing in children aged 5½ to 6 years born very preterm who have working memory impairment. Design, Setting, and Participants: This multicenter (18 French university hospitals), open-label randomized clinical trial with 2 parallel groups (EPIREMED) was conducted from November 2016 to April 2018, with the last follow-up during August 2019. Eligible children from the EPIPAGE 2 cohort were aged 5½ to 6 years, were born between 24 and 34 weeks' gestation, and had a global intelligence quotient greater than 70 and a working memory index less than 85. Data were analyzed from February to December 2020. Intervention: Children were randomized 1:1 to standard care management and a working memory cognitive training program (Cogmed software) for 8 weeks (25 sessions) (intervention) or to standard management (control). Main Outcomes and Measures: The primary outcome was the visuospatial index score from the Wechsler Preschool and Primary Scale of Intelligence, 4th Edition. Secondary outcomes were working memory, intellectual functioning, executive and attention processes, language skills, behavior, quality of life, and schooling. Neurobehavioral assessments were performed at inclusion and after finishing training at 6 months (intermeditate assessment; secondary outcomes) and at 16 months (final assessment; primary outcome). Results: There were 169 children randomized, with a mean (SD) age of 5 years 11 months (2 months); 91 (54%) were female. Of the participants, 84 were in the intervention group (57 of whom [68%] completed at least 15 cognitive training sessions) and 85 were in the control group. The posttraining visuospatial index score was not different between groups at a mean (SD) of 3.0 (1.8) months (difference, -0.6 points; 95% CI, -4.7 to 3.5 points) or 12.9 (2.6) months (difference, 0.1 points; 95% CI, -5.4 to 5.1 points). The working memory index score in the intervention group significantly improved from baseline at the intermediate time point (difference, 4.7 points; 95% CI, 1.2-8.1 points), but this improvement was not maintained at the final assessment. Conclusions and Relevance: This randomized clinical trial found no lasting effect of a cognitive training program on visuospatial processing in children aged 5½ to 6 years with working memory disorders who were born very preterm. The findings suggest that this training has limited long-term benefits for improving executive function. Transient benefits seemed to be associated with the developmental state of executive functions. Trial Registration: ClinicalTrials.gov Identifier: NCT02757794.

Risk factors associated with necrotizing enterocolitis in preterm infants: A case-control study.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common life-threatening gastrointestinal emergency in prematurity. The pathophysiology is multifactorial and remains incompletely understood. Early diagnosis and treatment could reduce the risk of mortality and morbidity. We aimed to identify factors associated with NEC in preterm newborns. METHOD: This case-control study included all preterm newborns presenting with NEC and managed between January 1, 2009 and December 31, 2018 in the neonatal intensive care unit of Nancy. For each case, two controls were matched according to three criteria: gestational age (WG), date of birth, and mode of delivery. Antenatal, peripartum, and postnatal risk factors prior to NEC were analyzed. RESULTS: A total of 292 infants were involved in the study, 113 of whom had NEC. Mean gestational age for newborns with NEC was 29 WG, and mean birth weight, 1340 g. Only early-onset infection was identified as a significant risk factor for NEC (15% vs. 6.6% for infection p<0.04, and 28.3% vs. 16.4% p<0.02 for infection and sepsis, NEC vs. controls, respectively). Late-onset feeding and initial continuous enteral feeding were significantly associated with the occurrence of more severe NEC (p<0.02 and p = 0.03, respectively). CONCLUSION: The results of this study are consistent with intestinal dysbiosis being a risk factor for NEC. Early-onset infection was found to be a significant risk factor. Enteral feeding practice may also be associated with NEC.

Infant exposure to Fluvoxamine through placenta and human milk: a case series - A contribution from the ConcePTION project.

Introduction: Fluvoxamine is widely used to treat depression during pregnancy and lactation. However, limited data are available on its transfer to the fetus or in human milk. This case series provides additional information on the infant exposure to fluvoxamine during pregnancy and lactation. Case presentation: Two women, aged 38 and 34 years, diagnosed with depression were treated with 50 mg fluvoxamine during pregnancy and lactation. At delivery a paired maternal and cord blood sample was collected for each woman. The first mother exclusively breastfed her child for 4 months and gave one foremilk and one hindmilk sample at 2 days and 4 weeks post-partum, whereas the second mother did not breastfeed. Results: The cord to plasma concentration ratios were 0.62 and 0.48, respectively. At 2 weeks post-partum, relative infant doses (RID) were 0.47 and 0.57% based on fluvoxamine concentrations in foremilk and hindmilk, respectively. At 4 weeks post-partum, the RIDs were 0.35 and 0.90%, respectively. The child from the first mother was born healthy and showed a normal development at the 6th, 18th and 36th month follow-ups. One of the twins from the second woman was hospitalized for hypoglycemia that was attributed to gestational diabetes and low birth weight. The second one was born healthy. Conclusion: These results suggest a minimal exposure to fluvoxamine during lactation which is in accordance with previously published data. Larger clinical and pharmacokinetic studies assessing the long-term safety of this drug during lactation and the variability of its exposure through breastmilk are warranted.

Neurodevelopment at seven years and parents' feelings of prematurely born children.

Background: The evolution of knowledge and technical advances in neonatal resuscitation have improved the survival of very premature babies. However, the long-term neurodevelopmental prognosis and cognitive and learning abilities are still uncertain. Objective: This study aimed to evaluate the neurodevelopment and learning abilities of 7-year-old children born prematurely, and their parents' feelings at 8 years of age. Patients and methods: Data from children born before 33 weeks gestation in a level III maternity hospital and involved in a regional follow-up network were analyzed at 7 years of age. Neurodevelopmental abnormalities were defined as cerebral palsy, hearing or visual impairment, and/or behavioral abnormalities. School performance was evaluated by the EDA test. A parents' questionnaire assessed their feelings about the child's and family's quality of life at 8 years of age. Results: At 7 years of age, 51% of the 238 children presented neurodevelopmental abnormalities: 3.3% with cerebral palsy, 6.2% with hearing impairments, 50.7% with visual impairments, and 11.3% with behavioral disorders. The children with neurodevelopmental abnormalities had lower gestational age (29.0 ± 2.0 vs. 30.0 ± 2.1 weeks, p = 0.003) and more EEG abnormalities during the neonatal period (31.1% vs. 19.8%, p = 0.048) than the children without abnormalities. Ninety-four percent of the children with abnormalities were enrolled in normal schools, 33% with special support. In the overall cohort, 31% of the children had all academic performance scores in the normal range of the reference population. At 8 years old, 39% of the parents of children with neurodevelopmental abnormalities felt that their child's situation significantly impacted their quality of life compared to 14% of parents of children without neurodevelopmental abnormality (p = 0.022). Conclusion: Half of children born very prematurely present with long-term neurodevelopmental abnormalities, which their parents feel significantly impacts their quality of life.

Influence of body mobility on attention networks in school-aged prematurely born children: A controlled trial.

School-aged prematurely born children (PC) have a higher risk of academic difficulties, which may be partly explained by attention difficulties. It has been suggested that children's attentional performance might be influenced by their body posture and spontaneous body motion. The aim of this study (ClinicalTrials.gov - NCT03125447) was to test the influence of three body mobility conditions on the three functions of attention (alertness, orienting, and executive control) among school-aged PC vs. term-born children (TC). Notably, 21 PC and 21 TC performed the Attention Network Test for Children in three body mobility conditions, namely, sitting and standing imposed fixed postures and a free-to-move condition. The children's median reaction times were compared between trials (1) with and without alerting cues, (2) with valid and invalid orienting cues, and (3) with and without distracting information, to calculate the performance of alertness, orienting, and executive control, respectively. Results showed that with distracting information, PC exhibited significantly slower responses in the standing-still posture than in the sitting-still posture (1,077 ± 240 vs. 1,175 ± 273 ms, p < 0.05), but not TC. No difference was observed with the free-to-move condition. PC and TC did not significantly differ in alertness or orienting, regardless of body mobility condition. These data suggest that PC must use executive resources to stand still and maintain position, which impairs their performance during executive tasks. We speculate that these results may be related to less developed postural control and motor inhibition in PC.

Use of a Liquid Supplement Containing 2 Human Milk Oligosaccharides: The First Double-Blind, Randomized, Controlled Trial in Pre-term Infants.

There is growing evidence supporting the benefit of human milk oligosaccharides (HMOs) on reducing risk of illnesses and improving immune function in newborn infants, but evidence in pre-term infants is lacking. This randomized, double-blind, placebo-controlled trial (NCT03607942) of pre-term infants evaluated the effects of HMO supplementation on feeding tolerance, growth, and safety in 7 neonatal units in France. Pre-term infants (27-33 weeks' gestation, birth weight <1,700 g) were randomized early after birth to receive HMO supplement (n = 43) [2'-fucosyllactose (2'FL) and lacto-N-neotetraose (LNnT) in a 10:1 ratio (0.374 g/kg body weight/day)] or an isocaloric placebo (n = 43) consisting of only glucose (0.140 g/kg/day) until discharge from the neonatal unit. Anthropometric z-scores were calculated using Fenton growth standards. Primary outcome was feeding tolerance, measured by non-inferiority (NI) in days to reach full enteral feeding (FEF) from birth in HMO vs. placebo group (NI margin = 4+ days). Mean number of days on intervention prior to FEF was 8.9 and 10.3 days in HMO and placebo, respectively. Non-inferiority in time to reach FEF in HMO (vs. placebo) was achieved [LS mean difference (95% CI) = -2.16 (-5.33, 1.00); upper bound of 95% CI < NI margin] in full analysis set and similar for per protocol. Adjusted mean time to reach FEF from birth was 2 days shorter in HMO (12.2) vs. placebo (14.3), although not statistically significant (p = 0.177). There was no difference in weight-for-age z-scores between groups throughout the FEF period until discharge. Length-for-age z-scores were higher in HMO at FEF day 14 [0.29 (0.02, 0.56), p = 0.037] and 21 [0.31 (0.02, 0.61), p = 0.037]. Head circumference-for-age z-score was higher in HMO vs. placebo at discharge [0.42 (0.12, 0.71), p = 0.007]. Occurrence of adverse events (AEs) was similar in both groups and relatively common in this population, whereas 2.3 and 14.3%, respectively, experienced investigator-confirmed, related AEs. HMO supplementation is safe and well-tolerated in pre-term infants. After 9 days of supplementation, the HMO group reached FEF 2 days earlier vs. placebo, although the difference was not statistically significant. In addition, HMO supplementation supports early postnatal growth, which may have a positive impact on long-term growth and developmental outcomes.

Body Mobility and Attention Networks in 6- to 7-Year-Old Children.

Learning in 6- to 7-year-old children is strongly influenced by three functions of attention: alertness, orienting, and executive control. These functions share a close relationship with body mobility, such as the posture adopted or a request to stay still during tasks. The aim of this study (ClinicalTrials.gov) was to analyze the influence of body posture (standing versus sitting) and the influence of these imposed postures compared to a free body mobility on attention functions in 6- to 7-year-old children. Twenty-one children (11 girls) with a mean age of 6.7±0.6years performed the Attention Network Test for Children in three-body mobility conditions: sitting still, standing still, and free to move. Three attentional scores were calculated which would separately reflect performance of alertness, orienting, and executive control. Overall, no difference in alertness performance was found between the three bodily mobility conditions. In addition, our results suggest a general poor orienting performance in children, whatever the body mobility condition, which might be related to their young age. Finally, children improved their executive control performance when they stood still, probably due to an improvement in arousal and mental state.

Outcome of Very Premature Newborn Receiving an Early Second Dose of Surfactant for Persistent Respiratory Distress Syndrome.

Background: Infants presenting respiratory distress syndrome (RDS) not responding to surfactant often receive a second instillation. Few studies evaluated the consequences of this second administration. This study aimed at determining the outcome of infants presenting persistent RDS and receiving an early second dose of surfactant. Methods: Infants below 32 weeks' gestation who received a second dose of 100mg/kg of surfactant within the first 72 h of life, were retrospectively involved in this 42 months' study. They were matched to two controls receiving a single dose of 200mg/Kg based upon gender and gestational age. Results: 52/156 infants receiving two doses (Group 2-doses) were significantly more often SGA [22 (42%) vs. 21 (20%) p = 0.04] and outborn [29 (56%) vs. 13 (12%) p = 0.001]. They had received antenatal corticos teroid therapy less often [26 (50%) vs. 89 (86%) p = 0.001] and presented more severe RDS based upon FiO2 level, oxygenation index and radiography. Group 2-doses survival was lower (65.4% vs. 79.6 % p < 0.1) but surviving infants did not have different morbidity than controls. Discussion: Premature newborn receiving a second dose of surfactant had adverse antenatal characteristics, presented more severe RDS and only partially responded to the first dose. Outcomes of surviving infants who received 2 doses of surfactant were comparable to others.

Microbiota and Human Milk Oligosaccharides in Premature Infants.

Gut microbiota plays an important role in infants' health. The prevalence of bifidobacteria in the gastrointestinal tract of term breastfed infants has been associated with reduced infection rates compared with formula-fed infants. However, few studies evaluated microbiota in premature infants. In an observational study of 577 preterm newborns born below 32 weeks gestation, gut microbiota was not driven by bifidobacteria but could be classified into six different clusters with regard to the most abundant bacteria present. Clusters were related to infants' maturity, perinatal determinants, and were associated with short- and long-term outcome. In another study, the effects of caesarean birth on infant gut microbiota could be alleviated by human milk oligosaccharides (HMOs) in mothers' milk. In addition, 58 infants fed with a formula enriched with 2 HMOs had microbiota closer to breastfed infants than 63 infants receiving the same formula without HMOs. The question then arose of the benefit of HMO supplementation for microbiota in premature infants. Thus, a multicenter randomized controlled intervention study of the effect of a liquid supplement containing 2 HMOs was set up. Ongoing data analysis will evaluate gastrointestinal tolerance parameters, intake of HMOs from human milk, long-term growth outcomes, fecal microbiota, and fecal biomarkers of gut maturation and immunity.

Case Series of COVID-19 Asymptomatic Newborns With Possible Intrapartum Transmission of SARS-CoV-2.

Background: Despite the pandemic, data are limited regarding COVID-19 infection in pregnant women and newborns. This report aimed to bring new information about presentation that could modify precautionary measures for infants born of mothers with a remote history of COVID-19. Methods: We report two infants with possible maternofetal transmission, and four mothers without immunologic reactions. Data were collected from the patient files. Results: One mother exhibited infection signs 10 days before uncomplicated delivery, with negative RT-PCR and no antibody detection thereafter. Another mother exhibited infection 6 weeks pre-delivery, confirmed by nasopharyngeal swab testing with positive RT-PCR, and positive antibody detection (IgM and IgG). Both newborns were asymptomatic but tested positive for nasopharyngeal and stool RT-PCR at 1 and 3 days of age for the first one and at 1 day of age for stool analysis for the second one. Two additional mothers exhibited infection confirmed by positive RT-PCR testing at 28- and 31-days pre-delivery but did not present detectable antibody reaction at the time of delivery. Conclusion: These observations raise concerns regarding contamination risk by asymptomatic newborns and the efficacy of immunologic reactions in pregnant mothers, questioning the reliability of antibody testing during pregnancy.

Impact of introducing a standardized nutrition protocol on very premature infants' growth and morbidity.

BACKGROUND: Inappropriate nutritional intake in premature infants may be responsible for postnatal growth restriction (PGR) and adverse long-term outcomes. OBJECTIVE: We evaluated the impact of an updated nutrition protocol on very premature infants' longitudinal growth and morbidity, and secondly the compliance to this new protocol. DESIGN: All infants born between 26-32 weeks gestation (GA) were studied retrospectively during two 6-month periods before (group 1) and after (group 2) the introduction of an optimized nutrition protocol, in a longitudinal comparative analysis. RESULTS: 158 infants were included; 72 before and 86 after the introduction of the protocol (Group 1: (mean±SD) birthweight (BW) 1154±276 g, GA 29.0±1.4 weeks; Group 2: BW 1215±332 g, GA 28.9±1.7 weeks). We observed growth improvement in Group 2 more pronounced in males (weight z-score) at D42 (-1.688±0.758 vs. -1.370±0.762, p = 0.045), D49 (-1.696±0.776 vs. -1.370±0.718, p = 0.051), D56 (-1.748±0.855 vs. -1.392±0.737, p = 0.072), D63 (-1.885±0.832 vs. -1.336±0.779 p = 0.016), and D70 (-2.001±0.747 vs. -1.228±0.765 p = 0.004). There was no difference in females or in morbidities between the groups. We observed low compliance to the protocol in both groups: similar energy intake but higher lipid intake in Group 1 and higher protein intake in Group 2. CONCLUSION: The quality of nutritional care with a strictly-defined protocol may significantly improve weight gain for very preterm infants. As compliance remained low, an educational reinforcement is needed to prevent PGR. CLINICAL TRIAL REGISTRATION: This retrospective study was registered by ClinicalTrials.gov under number NCT03217045, and by the CNIL (Commission Nationale de l'Informatique et des Libertés) under study number R2015-1 for the Maternity of the CHRU of Nancy.

Thyroxine Threshold Is Linked to Impaired Outcomes in Preterm Infants.

Transient hypothyroxinaemia of prematurity (THOP) presents as decreased free thyroxine without an increase in thyroid stimulating hormone. Thyroxine availability is important in case of premature birth, and THOP could be associated with impaired adaptation to extra-uterine life but the association of thyroxine level and clinical status has not yet been clearly defined. Aim: To defined a free thyroxine threshold likely associated with neonatal clinical impairment and outcomes at age three years. Methods: This retrospective cohort study included infants born before or at 28 weeks' gestation at the Regional Maternity in Nancy, France. We defined a free thyroxine threshold as a function of clinical impairment by Receiver Operating Curve analysis, validated by log likelihood iteration in binary logistic regression, in infants born from October 2008 to December 2012 and meeting neonatal clinical impairment criteria. This threshold was validated in a distinct cohort of infants born from January 2014 to December 2016. Clinical impairment was defined as assisted ventilation requirement at seven days of age plus four minor clinical disorders among heart rate, blood pressure, temperature, serum sodium and potassium, APGAR score at five minutes, vasopressor treatment and patent ductus arteriosus. The first cohort was assessed at age three years for neurodevelopmental outcomes. Results: We identified a ≤10 pmol/L threshold with 85.7% sensitivity and 51% specificity. From the first and second cohorts, 196 and 176 infants respectively had available data, and 85% (97/112) and 26% (20/78) with free thyroxine ≤10 pmol/L met clinical impairment criteria. For infants with values >10 pmol/L, 41% (35/84) and 3% (3/98) from the first and second cohorts met impairment criteria. Of 147 children with available data at age 3 years, 65% (58/89) with neonatal free thyroxine ≤10 pmol/L had adverse neurodevelopmental outcomes vs. 34% (20/58) with >10 pmol/L (OR 3.55; 95% confidence interval, 1.77-7.13; p < 0.001). Conclusion: A free thyroxine level ≤10 pmol/L in infants is associated with neonatal clinical impairment and poor outcome at age three years.

Early Effect of Supplemented Infant Formulae on Intestinal Biomarkers and Microbiota: A Randomized Clinical Trial.

BACKGROUND: Post-natal gut maturation in infants interrelates maturation of the morphology, digestive, and immunological functions and gut microbiota development. Here, we explored both microbiota development and markers of gut barrier and maturation in healthy term infants during their early life to assess the interconnection of gut functions during different infant formulae regimes. METHODS: A total of 203 infants were enrolled in this randomized double-blind controlled trial including a breastfed reference group. Infants were fed starter formulae for the first four weeks of life, supplemented with different combination of nutrients (lactoferrin, probiotics (Bifidobacterium animal subsp. Lactis) and prebiotics (Bovine Milk-derived Oligosaccharides-BMOS)) and subsequently fed the control formula up to eight weeks of life. Stool microbiota profiles and biomarkers of early gut maturation, calprotectin (primary outcome), elastase, α-1 antitrypsin (AAT) and neopterin were measured in feces at one, two, four, and eight weeks. RESULTS: Infants fed formula containing BMOS had lower mean calprotectin levels over the first two to four weeks compared to the other formula groups. Elastase and AAT levels were closer to levels observed in breastfed infants. No differences were observed for neopterin. Global differences between the bacterial communities of all groups were assessed by constrained multivariate analysis with hypothesis testing. The canonical correspondence analysis (CCA) at genus level showed overlap between microbiota profiles at one and four weeks of age in the BMOS supplemented formula group with the breastfed reference, dominated by bifidobacteria. Microbiota profiles of all groups at four weeks were significantly associated with the calprotectin levels at 4 (CCA, p = 0.018) and eight weeks of age (CCA, p = 0.026). CONCLUSION: A meaningful correlation was observed between changes in microbiota composition and gut maturation marker calprotectin. The supplementation with BMOS seems to favor gut maturation closer to that of breastfed infants.

Risk factors for bronchiolitis hospitalization in infants: A French nationwide retrospective cohort study over four consecutive seasons (2009-2013).

OBJECTIVES: Large studies are needed to update risk factors of bronchiolitis hospitalization. We performed a nationwide analysis of hospitalization rates for bronchiolitis over four consecutive bronchiolitis seasons to identify underlying medical disorders at risk of bronchiolitis hospitalization and assess their frequency. METHODS: Data were retrieved from the French National Hospital Discharge database. Of all infants discharged alive from maternity wards from January 2008 to December 2013 in France (N = 3,884,791), we identified four consecutive cohorts at risk of bronchiolitis during the seasons of 2009-2010 to 2012-2013. The main outcome was bronchiolitis hospitalization during a season. Individual risk factors were collected. RESULTS: Among infants, 6.0% were preterm and 2.0% had ≥1 chronic condition including 0.2% bronchopulmonary dysplasia (BPD) and 0.2% hemodynamically significant congenital heart disease (HS-CHD). Bronchiolitis hospitalization rates varied between seasons (min: 1.26% in 2010-2011; max: 1.48% in 2012-2013; p<0.001). Except omphalocele, the following conditions were associated with an increased risk for bronchiolitis hospitalization: solid organ (9.052; 95% CI, 4.664-17.567) and stem cell transplants (6.012; 95% CI, 3.441-10.503), muscular dystrophy (4.002; 95% CI, 3.1095-5.152), cardiomyopathy (3.407; 95% CI, 2.613-4.442), HS-CHD (3.404; 95% CI, 3.153-3.675), congenital lung disease and/or bronchial abnormalities, Down syndrome, congenital tracheoesophageal fistula, diaphragmatic hernia, pulmonary hypertension, chromosomal abnormalities other than Down syndrome, hemodynamically non-significant CHD, congenital abnormalities of nervous system, cystic fibrosis, cleft palate, cardiovascular disease occurring during perinatal period, and BPD. CONCLUSION: Besides prematurity, BPD, and HS-CHD, eighteen underlying conditions were associated with a significant increased risk for bronchiolitis hospitalization in a nationwide population.

A population pharmacokinetic model for escitalopram and its major metabolite in depressive patients during the perinatal period: Prediction of infant drug exposure through breast milk.

BACKGROUND AND OBJECTIVES: Escitalopram (SCIT) is frequently prescribed to breastfeeding women. Available information on SCIT excretion into breast milk is based on heterogeneous and incomplete data. A population pharmacokinetic model that aimed to better characterize maternal and infant exposure to SCIT and its metabolite was developed. METHODS: The study population was composed of women treated by SCIT or racemic citalopram and enrolled in the multicenter prospective cohort study SSRI-Breast Milk study (ClinicalTrial.gov NCT01796132). A joint structural model was first built for SCIT and S-desmethylcitalopram (SDCIT) in plasma using NONMEM and the milk-to-plasma ratio (MPR) was estimated by adding the drug breast milk concentrations. The effect of different influential covariates was tested and the average drug exposure with variability through breastfeeding was predicted under various conditions by simulation. RESULTS: The study enrolled 33 patients treated with SCIT or racemic citalopram who provided 80 blood and 104 milk samples. Mean MPR for both parent drug and metabolite was 1.9. Increased milk fat content was significantly associated with an increased drug transfer into breast milk (+28% for SCIT and +18% for SDCIT when fat amount doubles from 3.1 to 6.2 g/100 mL). Simulations suggested that an exclusively breastfed infant would ingest daily through breast milk 3.3% of the weight-adjusted maternal SCIT dose on average. CONCLUSION: The moderate between-subject variability in milk concentration of SCIT and the limited exposure to escitalopram through breast milk observed provide reassurance for treated mothers of breastfed healthy infants.

Networks as culture: understanding and accounting for risks within networks of medico-social actors.

The anthropological part of the present research project addresses the issue of risk and uncertainties relating to perinatality and disability, and draws from the discourses of professionals in a perinatal network in the French Lorraine region. From an anthropological point of view, it is necessary to determine how and to what extent the views of professionals determine the network's management policies. The place conferred to 'the user' in these representations is one of several important issues to be analysed in order to gain better understanding of the management of relationships that result from it. What is the position of professionals who 'negotiate' and 'organise' the cost of the risk of disability when grasped in connection with their images of the 'users' (children and parents)? This qualitative study consisted of 40 semi-structured interviews conducted with 20 medical, social, and community professionals, all involved directly or indirectly with the network. The results demonstrate the importance of a network assessment as a 'culture' from the social and cultural relations of network professionals. These relations form the cement of a structure made of interpersonal ties and rooted in particular histories around a 'user' that are conveyed through individual narratives.