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Isabelle Sommer,1– 4 David Palmero,1 Céline Julie Fischer Fumeaux,5 Pascal Bonnabry,3,4,6 Lucie Bouchoud,6 Farshid Sadeghipour1– 4 1Service of Pharmacy, Lausanne University Hospital, Lausanne, Switzerland; 2Center for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; 3School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland; 4Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland; 5Clinic of Neonatology, Department Woman Mother Child, Lausanne University Hospital, Lausanne, Switzerland; 6Service of Pharmacy,Geneva University Hospital, Geneva, SwitzerlandCorrespondence: Isabelle Sommer Service of Pharmacy, Lausanne University Hospital, Lausanne, SwitzerlandTel +41 79 556 63 59Email Isabelle.sommer@chuv.chBackground: There are variable practices in the management of the parenteral nutrition (PN) process in hospitals having a neonatal intensive care unit (NICU). In our hospital, PN is prepared partially on the neonatal ward by nurses but also at the central pharmacy by trained pharmacy technicians. A previous study showed a concentration non-conformity of 34% of on-ward PN preparations potentially resulting in under- or overfeeding of the patients.Objective: The objectives were to perform preliminary risk analyses (PRA) in preparation for our hospital’s transition to universal central pharmacy PN compounding.Methods: A working group including pharmacists, neonatologists, nurses, and pharmacy technicians performed two PRA. The risks of 9 management steps of the PN process were identified, evaluated, and quoted. A comparison of the number of risks and their criticality index (CI) was conducted.Results: A total of 36 and 39 risks were identified for PN preparation in the NICU and the pharmacy, respectively. For the NICU, ten risks (28%) had an “acceptable” CI, 15 risks (42%) were “under control” and eleven (31%) were defined as “non-acceptable”. For the pharmacy, 14 risks (36%) had an “acceptable” CI, 19 risks (49%) were “under control” and six (15%) were defined as “non-acceptable”. Risks directly related to the preparation process, including the steps preparation hood, PN preparation and analytical quality control, represented a cumulated CI of 145 for eleven NICU-risks vs 108 for twelve pharmacy risks (− 26%). The implementation of immediate improvement measures, eg, an electronic prescription form, reduces the total CI by 5.7% and 2.2% for the NICU and the pharmacy, respectively.Conclusion: This PRA highlighted the safety differences between PN preparation in the NICU vs the pharmacy at our institution, and facilitated our moving forward with a process change that should improve the care of our neonatal patients. Nevertheless, long-term improvement measures have to be implemented to further reduce risks related to the PN management process.Keywords: parenteral nutrition, drug compounding, risk assessment, standardization, neonatology, preterm infants

Aims: Sertraline is frequently prescribed for mental health conditions in both pregnant and breastfeeding women. According to the limited available data, only small amounts of sertraline are transferred into human milk, yet with a large amount of unexplained interindividual variability. This study aimed to develop a population pharmacokinetic (popPK) model to describe the pharmacokinetics of sertraline during the perinatal period and explain interindividual variability., Methods: Pregnant women treated with sertraline were enrolled in the multicenter prospective cohort SSRI-Breast Milk study. A popPK model for sertraline maternal plasma and breast milk concentrations was developed and allowed estimating the milk-to-plasma ratio (MPR). An additional fetal compartment allowed cord blood concentrations to be described. Several covariates were tested for significance. Ultimately, model-based simulations allowed infant drug exposure through placenta and breast milk under various conditions to be predicted., Results: Thirty-eight women treated with sertraline were included in the study and provided 89 maternal plasma, 29 cord blood and 107 breast milk samples. Sertraline clearance was reduced by 42% in CYP2C19 poor metabolizers compared to other phenotypes. Doubling milk fat content increased the MPR by 95%. Simulations suggested a median daily infant dosage of 6.9 μg kg -1 after a 50 mg maternal daily dose, representing 0.95% of the weight-adjusted maternal dose. Median cord blood concentrations could range from 3.29 to 33.23 ng mL -1 after maternal daily doses between 25 and 150 mg., Conclusions: Infant exposure to sertraline, influenced by CYP2C19 phenotype and breast milk fat content, remains low, providing reassurance regarding the use of sertraline during pregnancy and breastfeeding., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Introduction: Neonatal linear immunoglobulin A (IgA) bullous dermatosis (NLABD) is a rare, life-threatening, mucocutaneous bullous disorder. The pathogenesis and optimal treatment remain poorly defined and raise critical clinical challenges., Case Presentation: We present a case of a full-term female infant with severe cutaneous and respiratory symptoms due to NLABD. Diagnosis was confirmed by immunofluorescence on the infant's skin biopsy, while IgAs directed against the basement membrane of the skin and mucosa were identified in the mother's milk. The infant fully recovered after nearly 8 weeks of intensive multidisciplinary care, including non-invasive ventilation, nutritional support, wound care, systemic corticoid treatment, and breastfeeding discontinuation., Conclusion: This case underscores the importance of timely adequate diagnosis and management of this rare and serious condition. Moreover, it adds novel evidence documenting the presence of pathogenic IgAs in breastmilk., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Interactions between stimuli from different sensory modalities and their integration are central to daily life, contributing to improved perception. Being born prematurely and the subsequent hospitalization can have an impact not only on sensory processes, but also on the manner in which information from different senses is combined-i.e., multisensory processes. Very preterm (VPT) children (<32 weeks gestational age) present impaired multisensory processes in early childhood persisting at least through the age of five. However, it remains largely unknown whether and how these consequences persist into later childhood. Here, we evaluated the integrity of auditory-visual multisensory processes in VPT schoolchildren. VPT children (N = 28; aged 8-10 years) received a standardized cognitive assessment and performed a simple detection task at their routine follow-up appointment. The simple detection task involved pressing a button as quickly as possible upon presentation of an auditory, visual, or simultaneous audio-visual stimulus. Compared to full-term (FT) children (N = 23; aged 6-11 years), reaction times of VPT children were generally slower and more variable, regardless of sensory modality. Nonetheless, both groups exhibited multisensory facilitation on mean reaction times and inter-quartile ranges. There was no evidence that standardized cognitive or clinical measures correlated with multisensory gains of VPT children. However, while gains in FT children exceeded predictions based on probability summation and thus forcibly invoked integrative processes, this was not the case for VPT children. Our findings provide evidence of atypical multisensory profiles in VPT children persisting into school-age. These results could help in targeting supportive interventions for this vulnerable population., (© 2024. The Author(s).)

While the survival rate of very preterm (VPT) infants has increased in the last decades, they are still at risk of developing long-term neurodevelopmental impairments, especially regarding self-regulatory abilities, and goal-directed behaviors. These skills rely on executive functions (EFs), an umbrella term encompassing the core capacities for inhibition, shifting, and working memory. Existing comprehensive tests are time-consuming and therefore not suitable for all pediatric neuropsychological assessments. The Flanker task is an experimental computer game having the advantage to last less than ten minutes while giving multiple EFs measures. Here, we tested the potency of this task in thirty-one VPT children aged 8-10 years during their clinical assessment. First, we found that VPT children performed in the norm for most clinical tests (i.e., WISC-V, BRIEF, and NEPSY) except for the CPT-3 where they were slower with more omission errors, which could indicate inattentiveness. Second, some Flanker task scores were correlated with standardized clinical testing without resisting to multiple comparisons correction. Finally, compared to full-term children, VPT children showed poorer performance in global EFs measure and lower accuracy in the Flanker task. These findings suggest that this child-friendly version of the Flanker task demonstrated a reasonable sensitivity in capturing EFs with good discrimination between VPT and term children despite VPT children's mild difficulties. It may represent a promising tool for neuropsychological assessments and be suitable as a screening test, providing further validating larger studies. Moreover, while VPT schoolchildren globally display normal intelligence, subtle difficulties that seem to relate to EFs are observed.

Medication intake during the postpartum period is common with discontinuation of breastfeeding sometimes unnecessarily recommended for fear of adverse effects in the breastfed infant, while exposure through human milk is generally low. The assessment of risks associated with medication intake during breastfeeding is based, among other things, on the little clinical evidence available in specialized sources of information, and on pharmacokinetic principles. A decision-making support is presented to facilitate communication with mothers, foster medication adherence and prevent unnecessary interruption of breastfeeding., Competing Interests: Les auteur-es n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Donor human milk is the recommended alternative for feeding preterm or low birth weight infants when the mother's own milk is unavailable or not in sufficient quantity. Globally, the needs of vulnerable infants for donor human milk exceed the supply. This review aimed to identify the factors impacting the sustainability of human milk donation to milk banks. A systematic review of the literature was performed on eight databases to retrieve articles published until December 2021. The study protocol is available in PROSPERO (#CRD42021287087). Among the 6722 references identified, 10 studies (eight quantitative observational and two qualitative) met the eligibility criteria for a total of 7053 participants. Thirty factors influencing the sustainability of the donations to milk banks were identified and categorized as follows: (1) donation duration, (2) donors' infant features (e.g., gestational age, birth weight), (3) donors' features (e.g., socio-demographic characteristics, milk donation history), and (4) factors related to the milk bank and health care systems (awareness and support). The available evidence suggests that larger volumes of donated milk are associated with a longer duration of donation, as are early donation, previous milk donation, and donors with an infant of smaller weight and gestational age. Supporting and encouraging early donation and recruiting donors with infants of low birth weight and low gestational age could support longer donation times and greater volumes of milk donated. To identify efficient strategies and to draw appropriate recommendations to improve donor milk access, future studies should further explore the issues of the sustainability of human milk donation to milk banks.

We aimed to investigate whether the participation in an observational study on breastfeeding (Doal) modified breastfeeding outcomes in enrolling neonatal intensive care units (NICUs). This bi-centric before-and-after study included neonates who were admitted during a 4-month period before and a 4-month period after the implementation of Doal. Breastfeeding intention and breastfeeding rates at discharge were compared between the two periods. The association between inclusion in Doal and breastfeeding at discharge was assessed among the infants fulfilling the inclusion criteria of Doal. The present study included 655 neonates. After adjustments, both breastfeeding (aOR 1.21, 95%CI [1.1; 1.4], p = 0.001) and exclusive breastfeeding (aOR 1.8, 95%CI [1.4; 2.3], p < 0.001) at discharge increased in the period after. Breastfeeding intention was higher in one center in the period after (79%) compared to before (59%, p = 0.019). Compared to the period before, neonates who were not included in Doal in the period after had a lower chance to be breastfed at discharge, whereas those included were more frequently exclusively breastfed. The participation in an observational study on breastfeeding was associated with an increase in breastfeeding outcomes in enrolling neonatal intensive care units (NICUs). Patients who are not included deserve attention as they are at risk to be disadvantaged regarding breastfeeding success.

Mother's own milk (MOM) is ideal for infant growth and health. When MOM is unavailable, donor human milk (DHM), rather than infant formula, is recommended for at-risk, preterm or sick neonates (NN), in view of its protective effects. Human milk banks (HMB) collect, secure, process and distribute DHM. In Switzerland, there is insufficient and unequal access to DHM in the absence of a national policy framework. With the support of the State of Vaud, the CHUV and the Interregional Blood Transfusion of the Swiss Red Cross will open the first HMB in Romandy in 2022. This HMB offers an innovative system in Switzerland, based on complementary expertise, in order to guarantee the quality and safety of DHM and to support the promotion of breastfeeding and human milk donation., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Objective: To determine the frequency, type, and severity of adverse events (AEs) during intrahospital transport of newborn infants and to identify associated factors., Study Design: We conducted a prospective observational study in a tertiary care academic neonatal unit. All patients hospitalized in the neonatal unit and undergoing intrahospital transport between June 1, 2015, and May 31, 2017 were included. Transports from other hospitals and the delivery room were not included., Results: Data from 990 intrahospital transports performed in 293 newborn infants were analyzed. The median postnatal age at transport was 13 days (Q1-Q3, 5-44). Adverse events occurred in 25% of transports (248/990) and were mainly related to instability of cardiovascular and respiratory systems, agitation, and temperature control. Adverse events were associated with no harm in 207 transports (207/990, 21%), mild harm in 37 transports (37/990, 4%), and moderate harm in 4 transports (4/990, 0.4%). There was no severe or lethal adverse event. Hemodynamic support with catecholamines, the presence of a central venous catheter, and a longer duration of transport were independent predictors for the occurrence of adverse events during transport., Conclusions: Intrahospital transports of newborns are associated with a substantial proportion of adverse events of low-to-moderate severity. Our data have implications to inform clinical practice, for benchmarking and quality improvement initiatives, and for the development of specific guidelines., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Differences in vitamin and carotenoids content of human milk (HM) produced for infants born at term and preterm is poorly understood. In this study, HM was collected weekly for four and two months post-partum for preterm and term groups, respectively. Nutrients of interest, from single full breast expressions were measured by liquid chromatography coupled with mass spectrometry. Microbiological assay was employed for vitamin B 12 . When compared at equivalent post-partum age, vitamins B 1 , B 2 , B 6 , and B 9 were significantly higher in preterm than in term HM, but only during the first two weeks. No significant differences were observed for A, E, B 3 and B 12 between groups. Lycopene was the only carotenoid exhibiting a significant higher concentration in term than in preterm HM between weeks 1 and 4 post-partum. When compared at equivalent post-menstrual age, preterm milk was significantly higher for vitamins B 1 , B 2 , B 3 , B 6 and B 9 and lower levels of vitamins A, E, β-carotene, β-cryptoxanthin, lutein, zeaxanthin and lycopene compared to their term counterparts. These results suggest that preterm breastfed infants at term equivalent age may receive lower amounts of these micronutrients than breast-fed term neonates, possibly highlighting the need to supplement or fortify their nutritional intake with vitamins and carotenoids. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT #02052245., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Aim: We aimed to identify variables associated with gestational age at full oral feeding in a cohort of very preterm infants., Methods: In this retrospective study, all infants born below 32 weeks of gestation and admitted to a level III neonatal unit in 2015 were included. We dichotomized our population of 122 infants through the median age at full oral feeding, and explored which variables were statistically different between the two groups. We then used linear regression analysis to study the association between variables known from the literature and variables we had identified and age at full oral feeding., Results: The median postnatal age at full oral feeding was 36 6/7weeks post menstrual age (Q1-Q3 35 6/7-392/7), and was associated with the duration of hospital of stay. In the univariable linear regression, the variables significantly associated with full oral feeding were gestational age, socioeconomic status, sepsis, patent ductus arteriosus, duration of supplementary oxygen, of non-invasive and invasive ventilation, and bronchopulmonary dysplasia. In the multivariable regression analysis, duration of non-invasive ventilation and oxygen therapy, bronchopulmonary dysplasia, and patent ductus arteriosus were associated with an older age at full oral feeding, with bronchopulmonary dysplasia the single most potent predictor., Discussion: Lung disease severity is a major determinant of age at full oral feeding and thus length of stay in this population. Other factors associated with FOF include socioeconomic status and patent ductus arteriosus, There is a need for research addressing evidence-based bundles of care for these infants at risk of long-lasting feeding and neurodevelopmental impairments., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Among preterm infants, mother's own milk feeding reduces neonatal morbidity and decreases the length of hospital stay. However, breastfeeding rates and duration are lower than among term infants. It is reported that peer counselling is effective in increasing breast feeding in term infants in low-income and middle-income countries, but results are mixed in high-income countries. We aim to investigate herein whether peer counselling may be a feasible and effective breastfeeding support among preterm infants in French-speaking high-income countries., Methods and Analysis: Eight European centres will participate in this stepped-wedge cluster randomised controlled trial. We plan to include 2400 hospitalised neonates born before 35 gestational weeks. Each centre will begin with an observational period. Every 3 months, a randomised cluster (centre) will begin the interventional period with peer counsellors until the end of the study. The counsellors will be trained and supervised by the trained nurses. They will have a weekly contact with participating mothers, with a face-to-face meeting at least once every fortnight. During these meetings, peer counsellors will listen to mothers' concerns, share experiences and help the mother with their own knowledge of breast feeding. The main outcome is breastfeeding rate at 2 months corrected age. Secondary outcomes are breastfeeding rates at hospital discharge and at 6 months, breastfeeding duration and severe neonatal morbidity and mortality. The mental health of the mother, mother-infant bonding and infant behaviour will be assessed using self-report questionnaires. A neurodevelopmental follow-up, a cost-effectiveness analysis and a cost-consequence at 2 years corrected age will be performed among infants in a French subgroup., Ethics and Dissemination: French, Belgian and Swiss ethics committees gave their agreement. Publications in peer-reviewed journals are planned on breast feeding, mental health and economic outcomes., Trial Registration Number: NCT03156946., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Gestational diabetes mellitus (GDM) exposes mothers and their offspring to short and long-term complications. The objective of this study was to identify the importance of potentially modifiable predictors of adverse outcomes in pregnancies with GDM. We also aimed to assess the relationship between maternal predictors and pregnancy outcomes depending on HbA1c values and to provide a risk stratification for adverse pregnancy outcomes according to the prepregnancy BMI (Body mass index) and HbA1c at the 1st booking., Methods: This prospective study included 576 patients with GDM. Predictors were prepregnancy BMI, gestational weight gain (GWG), excessive weight gain, fasting, 1 and 2-h glucose values after the 75 g oral glucose challenge test (oGTT), HbA1c at the 1st GDM booking and at the end of pregnancy and maternal treatment requirement. Maternal and neonatal outcomes such as cesarean section, macrosomia, large and small for gestational age (LGA, SGA), neonatal hypoglycemia, prematurity, hospitalization in the neonatal unit and Apgar score at 5 min < 7 were evaluated. Univariate and multivariate regression analyses and probability analyses were performed., Results: One-hour glucose after oGTT and prepregnancy BMI were correlated with cesarean section. GWG and HbA1c at the end pregnancy were associated with macrosomia and LGA, while prepregnancy BMI was inversely associated with SGA. The requirement for maternal treatment was correlated with neonatal hypoglycemia, and HbA1c at the end of pregnancy with prematurity (all p < 0.05). The correlations between predictors and pregnancy complications were exclusively observed when HbA1c was ≥5.5% (37 mmol/mol). In women with prepregnancy BMI ≥ 25 kg/m 2 and HbA1c ≥ 5.5% (37 mmol/mol) at the 1st booking, the risk for cesarean section and LGA was nearly doubled compared to women with BMI with < 25 kg/m 2 and HbA1c <  5.5% (37 mmol/mol)., Conclusions: Prepregnancy BMI, GWG, maternal treatment requirement and HbA1c at the end of pregnancy can predict adverse pregnancy outcomes in women with GDM, particularly when HbA1c is ≥5.5% (37 mmol/mol). Stratification based on prepregnancy BMI and HbA1c at the 1st booking may allow for future risk-adapted care in these patients.

Introduction : Depression affects 300 million individuals worldwide. While selective serotonin reuptake inhibitors (SSRI) are one of the first-line pharmacological treatments of major depression in the general population, there is still uncertainty regarding their potential benefits and risks during pregnancy. Areas covered : Outcomes requisite for a proper risk/benefit assessment of SSRI in pregnancy and lactation were considered: (a) potential risks associated with untreated depression, (b) effectiveness of different treatment options of depression, (c) potential risks associated with SSRI. Expert opinion : Despite the growing amount of literature on SSRI use during pregnancy, no new trials assessing the benefits of SSRIs on maternal depression were found. In the light of new data regarding the potential risks, depressed SSRI-treated pregnant women and their children seem at increased risk for several complications (mostly of small absolute risk). The interpretation of these findings remains quite similar to our previous review as the available methodology does not allow to disentangle the potential effect of SSRIs from those of the disease itself or/and of its unmeasured associated risk factors. Thus, in pregnant or lactating women who require a pharmacological treatment, SSRIs can still be considered as appropriate when effective as the abundant data support their relative safety.

We sought to establish guidelines for hygiene care in newborns based on a systematic review of the literature and grading of evidence using the Groupe de Réflexion et d'Evaluation de l'Environement des Nouveau-nés (GREEN) methodology. We examined 45 articles and 4 reports from safety agencies. These studies recommend a tub bath (rather than a sponge bath) for full-term infants and a swaddle bath for preterm newborns. They also recommend against daily cleansing of preterm infants. The literature emphasized that hygiene care must consider the clinical state of the newborn, including the level of awareness and behavioral responses. Hospitalized newborns treated with topical agents may also experience high exposure to potentially harmful excipients of interest. Caregivers should therefore be aware of the excipients present in the different products they use. In high-resource countries, the available data do not support the use of protective topical agents for preterm infants.Conclusions: We recommend individualization of hygiene care for newborns. There is increasing concern regarding the safety of excipients in topical agents that are used in neonatology. A multidisciplinary approach should be used to identify an approach that requires lower levels of excipients and alternative excipients. What is known: • Hygiene care is one of the most basic and widespread types of care received by healthy and sick newborns worldwide. • There is no current guideline on hygiene for preterm or hospitalized term newborn. What is new: • The French Group of Reflection and Evaluation of the environment of Newborns (GREEN) provided here guidelines based on the current body of evidence. • Caregivers should be aware of the many issues related to hygiene care of newborns including newborns' behavioral responses to hygiene care, exposition to excipients of interest, and the potential risk of protective topical agents in a preterm infant. provided here guidelines based on the current body of evidence. • Caregivers should be aware of the many issues related to hygiene care of newborns including newborns' possible behavioral responses to hygiene care, exposition to excipients of interest and the potential risk of protective topical agents in a preterm infant.

Background: Proteins are major contributors to the beneficial effects of human milk (HM) on preterm infant health and development. Alpha-lactalbumin, lactoferrin, serum albumin and caseins represent approximately 85% of the total HM protein. The temporal changes of these proteins in preterm (PT) HM and its comparison with term (T) HM is poorly characterized., Aims: To quantify and compare the temporal changes of the major proteins in PT HM and T HM., Methods: HM was collected for 4 months postpartum at 12 time points for PT HM (gestational age 28 0/7-32 6/7 weeks; 280 samples) and for 2 months postpartum at 8 time points for T HM (gestational age 37 0/7-41 6/7 weeks; 220 samples). Proteins were measured with a micro-fluidic LabChip system., Results: Casein, alpha-lactalbumin and lactoferrin decreased with advancing stages of lactation in PT and T HM, whereas serum albumin remained stable. Only marginal differences between PT and T HM were observed for alpha-lactalbumin during postpartum weeks 3-5 and for serum albumin at the first week. However, a comparison of HM provided to preterm and term infants at the same postmenstrual ages revealed that alpha-lactalbumin contents were significantly lower in PT HM than in T HM during the 39-48 postmenstrual weeks., Conclusions: This study provides comprehensive information of the longitudinal changes of major proteins in PT and T HM, and suggests limited availability of alpha-lactalbumin, a nutritionally important protein, in breastfed PT infants after reaching the term corrected age. This information may be important to optimize HM protein fortification, although its biological relevance needs to be confirmed by intervention studies., Clinical Trial Registry: ClinicalTrials.gov (NCT02052245), https://clinicaltrials.gov/ct2/show/NCT02052245., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Mother's own milk is the optimal source of nutrients and provides numerous health advantages for mothers and infants. As they have supplementary nutritional needs, very preterm infants may require fortification of human milk (HM). Addressing HM composition and variations is essential to optimize HM fortification strategies for these vulnerable infants., Aims: To analyze and compare macronutrient composition in HM of mothers lactating very preterm (PT) (28 0/7 to 32 6/7 weeks of gestational age, GA) and term (T) infants (37 0/7 to 41 6/7 weeks of GA) over time, both at similar postnatal and postmenstrual ages, and to investigate other potential factors of variations., Methods: Milk samples from 27 mothers of the PT infants and 34 mothers of the T infants were collected longitudinally at 12 points in time during four months for the PT HM and eight points in time during two months for the T HM. Macronutrient composition (proteins, fat, and lactose) and energy were measured using a mid-infrared milk analyzer, corrected by bicinchoninic acid (BCA) assay for total protein content., Results: Analysis of 500 HM samples revealed large inter- and intra-subject variations in both groups. Proteins decreased from birth to four months in the PT and the T HM without significant differences at any postnatal time point, while it was lower around term equivalent age in PT HM. Lactose content remained stable and comparable over time. The PT HM contained significantly more fat and tended to be more caloric in the first two weeks of lactation, while the T HM revealed higher fat and higher energy content later during lactation (three to eight weeks). In both groups, male gender was associated with more fat and energy content. The gender association was stronger in the PT group, and it remained significant after adjustments., Conclusion: Longitudinal measurements of macronutrients compositions of the PT and the T HM showed only small differences at similar postnatal stages in our population. However, numerous differences exist at similar postmenstrual ages. Male gender seems to be associated with a higher content in fat, especially in the PT HM. This study provides original information on macronutrient composition and variations of HM, which is important to consider for the optimization of nutrition and growth of PT infants., Competing Interests: C.L.G.-R., C.A.D.C., M.-C.C.-C., S.K.T., and M.A. are all employees of Nestec Ltd.; C.J.F.F., L.B. and J.-F.T. declare no conflict of interest.

Human milk oligosaccharides (HMOs) are a major component of human milk, and play an important role in protecting the infant from infections. Preterm infants are particularly vulnerable, but have improved outcomes if fed with human milk. This study aimed to determine if the HMO composition of preterm milk differed from that of term milk at equivalent stage of lactation and equivalent postmenstrual age. In all, 22 HMOs were analyzed in 500 samples of milk from 25 mothers breastfeeding very preterm infants (< 32 weeks of gestational age, < 1500g of birthweight) and 28 mothers breastfeeding term infants. The concentrations of most HMOs were comparable at equivalent postpartum age. However, HMOs containing α-1,2-linked fucose were reduced in concentration in preterm milk during the first month of lactation. The concentrations of a number of sialylated oligosaccharides were also different in preterm milk, in particular 3'-sialyllactose concentrations were elevated. At equivalent postmenstrual age, the concentrations of a number of HMOs were significantly different in preterm compared to term milk. The largest differences manifest around 40 weeks of postmenstrual age, when the milk of term infants contains the highest concentrations of HMOs. The observed differences warrant further investigation in view of their potential clinical impact., Competing Interests: S.A., C.A.D.C., N.S., A.B., M.A., and C.L.G.R. are all employees of Nestec Ltd. L.B., J.F.T. and C.J.F.F. declare no conflict of interest.

We longitudinally compared fatty acids (FA) from human milk (HM) of mothers delivering term and preterm infants. HM was collected for 4 months postpartum at 12 time points for preterm and for 2 months postpartum at 8 time points for term group. Samples were collected from the first feed of the morning, and single breast was fully expressed. FA were analyzed by gas chromatography coupled with flame ionization detector. Oleic, palmitic and linoleic acids were the most abundant FA across lactation and in both groups. Preterm colostrum contained significantly ( p < 0.05) higher 8:0, 10:0, 12:0, sum medium chain fatty acids (MCFA), 18:3 n-3 FA compared to term counterparts. Preterm mature milk contained significantly higher 12:0, 14:0, 18:2 n-6, sum saturated fatty acids (SFA), and sum MCFA. We did not observe any significant differences between the preterm and term groups for docosahexaenoic acid, arachidonic acid and eicosapentaenoic acid at any stage of lactation. Overall, preterm milk was higher for SFA with a major contribution from MCFA and higher in 18:2 n-6. These observational differences needs to be studied further for their implications on preterm developmental outcomes and on fortification strategies of either mothers' own milk or donor human milk.

Background: Optimizing early nutritional intake in preterm neonates may promote brain health and neurodevelopment through enhanced brain maturation. Our objectives were (1) to determine the association of energy and macronutrient intake in the first 2 weeks of life with regional and total brain growth and white matter (WM) maturation, assessed by 3 serial MRI scans in preterm neonates; (2) to examine how critical illness modifies this association; and (3) to investigate the relationship with neurodevelopmental outcomes., Methods: Forty-nine preterm neonates (21 boys, median [interquartile range] gestational age: 27.6 [2.3] weeks) were scanned serially at the following median postmenstrual weeks: 29.4, 31.7, and 41. The total brain, basal nuclei, and cerebellum were semiautomatically segmented. Fractional anisotropy was extracted from diffusion tensor imaging data. Nutritional intake from day of life 1 to 14 was monitored and clinical factors were collected., Results: Greater energy and lipid intake predicted increased total brain and basal nuclei volumes over the course of neonatal care to term-equivalent age. Similarly, energy and lipid intake were significantly associated with fractional anisotropy values in selected WM tracts. The association of ventilation duration with smaller brain volumes was attenuated by higher energy intake. Brain growth predicted psychomotor outcome at 18 months' corrected age., Conclusions: In preterm neonates, greater energy and enteral feeding during the first 2 weeks of life predicted more robust brain growth and accelerated WM maturation. The long-lasting effect of early nutrition on neurodevelopment may be mediated by enhanced brain growth. Optimizing nutrition in preterm neonates may represent a potential avenue to mitigate the adverse brain health consequences of critical illness., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Background: Despite the critical importance of breast milk for preterm and sick neonates, there is no consensus regarding the use of raw mother's own milk (MOM) in neonatal units., Objectives: This study aimed to describe the use of raw MOM in hospitalised neonates before day 7 (early use), and to investigate: (i) related factors, (ii) maternal satisfaction, and (iii) the association with breastfeeding continuation., Methods: This prospective cohort included 516 neonates intended to be breastfed in 2 French neonatal units. Neonates receiving raw MOM before day 7 were compared to those who did not. The association between early use of MOM and breastfeeding continuation at hospital discharge, and up to 6 months later, was measured by logistic regression., Results: More than one-third (36.2%) of breastfed neonates did not receive any MOM during their first week, mainly due to organisational constraints and staff reluctance. Maternal satisfaction related to early raw MOM use was high (96%), and was coupled with a more frequent maternal feeling of being supported in breastfeeding (p = 0.003). There was a significant association between early use of MOM and breastfeeding continuation at discharge (OR 2.92, 95% CI 1.94-4.40, p < 0.0001), which persisted 6 months later (OR 2.70, 95% CI 1.21-6.03, p = 0.023). This association appeared independent in multivariable analyses (at discharge: aOR 2.03, 95% CI 1.27-3.25, p = 0.003; 6 months later: aOR 2.46, 95% CI 1.02-5.92, p = 0.045)., Conclusion: While the early use of raw MOM in hospitalised neonates can be limited by multiple factors, it appears supportive for mothers, and might represent a simple opportunity to improve breastfeeding in neonatal units., (© 2017 S. Karger AG, Basel.)

Objectives: To investigate the association between early nutritional intake and brain development assessed by magnetic resonance imaging (MRI)., Study Design: A cohort of neonates born at ≤30 weeks gestational age underwent MRI at term equivalent age. Brain maturation and injury were assessed using the Kidokoro score. Two groups were defined by severity of the scores. The associations between macronutrients intake during the first 2 weeks of life, clinical factors, and imaging scores were analyzed using logistic regression., Results: MRI scores from group 1 patients (n = 27) were normal to mildly abnormal (0-5). Group 2 (n = 15) had more abnormal scores (6-12). The median gestational ages (IQR) were 27.4 (1.9) weeks in group 1 and 27.0 (2.9) weeks in group 2, with birth weights of 900 (318) g (group 1) and 844 (293) g (group 2). In group 2, energy, lipid, and carbohydrate intake were significantly lower than in group 1. Group 2 also showed higher rates of sepsis and clinical risk scores than group 1. After adjustments in bivariate models, higher energy and lipid intake remained significantly associated with improved scores on MRI. This association was stronger for the gray matter component of the score., Conclusions: Higher energy and lipid intake during the first 2 weeks after birth was associated with a lower incidence of brain lesions and dysmaturation at term equivalent age in preterm neonates., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Nutrition is central in pediatric care : essential for growth and development, it plays also a role in the prevention of many diseases.Even if breastfeeding is highly recommended, its implementation may be difficult in particular for premature and ill newborns. The creation of a specific unit for breastfeeding support in neonatology allows to help mothers willing to nurse and to improve the rate of breastfeeding for these vulnerable infants.Eating disorders represent an important challenge for patient care. Early detection and rapid management of anorexia is essential for the prognosis. This article describes the challenges and the practical process underlying the development of a practical guideline to manage children and adolescents hospitalized for anorexia., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background & Aims: Hyperglycemia occurs in more than half of the extremely low birth weight (ELBW) neonates during the first weeks of life, and is correlated with an increased risk of morbi-mortality. Hypophosphatemia is another frequent metabolic disorder in this population. Data from animal, adult studies and clinical observation suggest that hypophosphatemia could induce glucose intolerance. Our aim was to determine whether a low phosphatemia is associated with hyperglycemia in ELBW neonates., Methods: This observational study included ELBW infants admitted in a tertiary neonatal care center (2010-2011). According to the center's policy, they received parenteral nutrition from birth and human milk from day 1. Phosphatemia and glycemia were measured routinely during parenteral nutrition. Hyperglycemia was defined by two consecutives values >8.3 mmol/L (150 mg/dL). Statistical analysis used a joint model combining a mixed-effects and a survival submodels to measure the association between phosphate and hyperglycemia., Results: The study included 148 patients. Mean gestational (Standard Deviation) age was 27.3 (1.6) weeks; mean birth weight was 803 (124) grams; 57% presented hyperglycemia. The multivariate joint model showed that the hazard of hyperglycemia at a given time was multiplied by 3 for each 0.41 mmol/L decrease of phosphate level at this time (p = 0.002) and by 3.85 for the same decreased of phosphate the day before (p = 0.0015)., Conclusion: To our knowledge, this is the first study suggesting that low phosphatemia can be associated with hyperglycemia in ELBW neonates. Further studies will have to demonstrate whether better control of phosphatemia could help in preventing hyperglycemia., (Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

This review includes five randomized controlled trials, published in the Medline database in 2015, which were selected by the Scientific commission of the French society of neonatology, taking into account their influence in perinatology. This selection was presented during the specific "Top five" session in the French congress of neonatal research., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Whether being small for gestational age (SGA) increases the risk of adverse neurodevelopmental outcome in premature infants remains controversial., Objective: to study the impact of SGA (birthweight < percentile 10) on cognition, behavior, neurodevelopmental impairment and use of therapy at 5 years old., Methods: This population-based prospective cohort included infants born before 32 weeks of gestation. Cognition was evaluated with the K-ABC, and behavior with the Strengths and Difficulties Questionnaire (SDQ). Primary outcomes were cognitive and behavioral scores, as well as neurodevelopmental impairment (cognitive score < 2SD, hearing loss, blindness, or cerebral palsy). The need of therapy, an indirect indicator of neurodevelopmental impairment, was a secondary outcome. Linear and logistic regression models were used to analyze the association of SGA with neurodevelopment., Results: 342/515 (76%) premature infants were assessed. SGA was significantly associated with hyperactivity scores of the SDQ (coefficient 0.81, p < 0.04), but not with cognitive scores, neurodevelopmental impairment or the need of therapy. Gestational age, socio-economic status, and major brain lesions were associated with cognitive outcome in the univariate and multivariate model, whereas asphyxia, sepsis and bronchopulmonary dysplasia were associated in the univariate model only. Severe impairment was associated with fetal tobacco exposition, asphyxia, gestational age and major brain lesions. Different neonatal factors were associated with the use of single or multiple therapies: children with one therapy were more likely to have suffered birth asphyxia or necrotizing enterocolitis, whereas the need for several therapies was predicted by major brain lesions., Discussion: In this large cohort of premature infants, assessed at 5 years old with a complete panel of tests, SGA was associated with hyperactive behavior, but not with cognition, neurodevelopmental impairment or use of therapy. Birthweight <10th percentile alone does not appear to be an independent risk factor of neurodevelopmental adverse outcome in preterm children.

There are growing concerns on long-term health consequences, notably on fertility rates, of plasticizers such as phthalates. While di(2-ethylhexyl)phthalate (DEHP) is currently used in several medical devices, newborns in the neonatal intensive care unit are both more exposed and more vulnerable to DEHP. The objectives of this study were to identify, count, and describe possible sources of DEHP in a neonatal care unit. Our method consisted in the listing and the inspection of the information on packaging, complemented by contact with manufacturers when necessary. According to the results, 6% of all products and 10% of plastic products contained some DEHP; 71% of these involved respiratory support devices. A vast majority of the items showed no information on the content of DEHP. Further research is needed, particularly to determine the effects of such an early exposure and to study and develop safer alternatives., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)