[Towards an ideal environment in neonatology]. / Vers un environnement idéal en néonatalogie.

The establishment of sensory systems occurs gradually along a transnatal continuum. During premature birth, hospitalization in neonatology, through its atypical sensory stimulations, can disrupt the development of the baby's still immature brain. To promote harmonious development in children, caregivers and parents must learn to take into account their sensory expectations in order to create the most suitable environment possible for their development.

Early skin-to-skin contact and risk of late-onset-sepsis in very and extremely preterm infants.

BACKGROUND: To evaluate the association between exposure to early skin-to-skin contact (SSC) and incidence of late-onset sepsis (LOS) in extremely and very preterm infants. METHODS: Observational study using the national population-based EPIPAGE-2 cohort in 2011. A propensity score for SSC exposure was used to match infants with and without exposure to SSC before day 4 of life and binomial log regression used to estimate risk ratios and CIs in the matched cohort. The primary outcome was at least one episode of LOS during hospitalization. Secondary outcomes were the occurrence of any late-onset neonatal infection (LONI), LOS with Staphylococcus or Staphylococcus aureus, incidence of LOS and LONI per 1000 central venous catheter days. RESULTS: Among the 3422 included infants, 919 were exposed to early SSC. The risk ratio (RR) for LOS was 0.86 (95% CI, 0.67-1.10), for LONI was 1.00 (95% CI, 0.83-1.21), and for LOS with Coagulase-negative Staphylococcus or Staphylococcus aureus infection was 0.91 (95% CI, 0.68-1.21) and 0.77 (95% CI, 0.31-1.87). The incidence RR for LOS per-catheter day was 0.87 (95% CI, 0.64-1.18). CONCLUSION: Early SSC exposure was not associated with LOS or LONI risk. Thus, their prevention should not be a barrier to a wider use of SSC. IMPACT: Kangaroo Mother Care decreased neonatal infection rates in middle-income countries. Skin-to-skin contact is beneficial for vulnerable preterm infants but barriers exist to its implementation. In a large population-based study using a propensity score methods, we found that skin-to-skin contact before day 4 of life was not associated with a decreased risk of late-onset-sepsis in very and extremely preterm infants. Early skin-to-skin contact was not associated with an increased risk of any late-onset-neonatal-infection, in particular with staphylococcus. The fear of neonatal infection should not be a barrier to a wider use of early skin-to-skin contact in this population.

French Neonatal Society issues recommendations on preventing nasal injuries in preterm newborn infants during non-invasive respiratory support.

AIM: To issue practical recommendations regarding the optimal care of nasal skin when non-invasive ventilation support is used. METHODS: We performed a systematic search of PubMed to identify relevant papers published in English or French through December 2019. Different grades of evidence were evaluated. RESULTS: Forty-eight eligible studies. The incidence in preterm infants was high. The lesions were more frequent for preterm infants born under 30 weeks of gestational age and/or below 1500 g. The lesion was most often located on the skin of the nose but could also be found on the intranasal mucous membranes or elsewhere on the face. Nasal injuries appear early after the beginning of non-invasive ventilation at a mean of 2-3 days for cutaneous lesions and eight or nine for intranasal lesions. The most effective strategies to prevent trauma are the use of a hydrocolloid at the beginning of the support ventilation, the preferential use of a mask and the rotation of ventilation interfaces. CONCLUSION: Nasal injuries with continuous positive airway pressure treatment in preterm newborn infants were frequent and can induce pain, discomfort and sequelae. The immature skin of preterm newborn infants needs specific attention from trained caregivers and awareness by parents.

The burden of early life stress on the nociceptive system development and pain responses.

For a long time, the capacity of the newborn infant to feel pain was denied. Today it is clear that the nociceptive system, even if still immature, is functional enough in the newborn infant to elicit pain responses. Unfortunately, pain is often present in the neonatal period, in particular in the case of premature infants which are subjected to a high number of painful procedures during care. These are accompanied by a variety of environmental stressors, which could impact the maturation of the nociceptive system. Therefore, the question of the long-term consequences of early life stress is a critical question. Early stressful experience, both painful and non-painful, can imprint the nociceptive system and induce long-term alteration in brain function and nociceptive behavior, often leading to an increase sensitivity and higher susceptibility to chronic pain. Different animal models have been developed to understand the mechanisms underlying the long-term effects of different early life stressful procedures, including pain and maternal separation. This review will focus on the clinical and preclinical data about early life stress and its consequence on the nociceptive system.

Optimising homeothermy in neonates: a systematic review and clinical guidelines from the French Neonatal Society.

AIM: Thermal instability is harmful on the newborn infant. We sought to draw up practical guidelines on maintaining homeothermy alongside skin-to-skin contact. METHODS: A systematic analysis of the literature identified relevant studies between 2000 and 2021 in the PubMed database. Selected publications were evaluated, and their level of evidence were graded, in order to underpin the development of clinical guidelines. RESULTS: We identified 7 meta-analyses and 64 clinical studies with a focus on newborn infants homeothermy. Skin-to-skin contact is the easiest and most rapidly implementable method to prevent body heat loss. Alongside skin-to-skin contact, monitoring the newborn infant's body temperature with a target of 37.0°C is essential. For newborn infants <32 weeks of gestation, a skullcap and a polyethylene bag should be used in the delivery room or during transport. To limit water loss, inhaled gases humidification and warming is recommended, and preterm infants weighing less than 1600 g should be nursed in a closed, convective incubator. With regard to incubators, there are no clear benefits for single vs. double-wall incubators as well as for air vs. skin servo control. CONCLUSION: Alongside skin-to-skin contact, a bundle of practical guidelines could improve the maintenance of homeothermy in the newborn infant.

Practical recommendations on room sizes for hospitalised newborn infants and their families based on a systematic review of the literature.

AIM: Neonatal unit design may affect the neurodevelopment of hospitalised neonates and the well-being of parents and healthcare staff (HCS). We aimed to provide recommendations regarding the minimum area required for a hospital room for a single neonate and their family. METHODS: We searched PubMed and Web of Science for relevant articles published from 1 January 2011 to 1 May 2021 by using the keywords NICU and facility design. Recommendations were developed after internal and external review by a multidisciplinary group including 15 professionals and parent representatives. RESULTS: We identified 314 studies and developed six recommendations from four eligible studies. Recommendations for room size were developed according to three perspectives: opinions of users, who emphasised the need for a spacious room; proposals of organisations by HCS, which advocated for a minimum floor area of 11.2-18 m2 in a single non-family room and 15.3-24 m2 in a single-family room; and simulation methods indicating that the minimum floor area in the neonatal unit should be 18.5-24 m2 . CONCLUSION: Units need to provide a minimum room size to allow for optimal newborn development and a better experience for parents and caregivers.

Association of Continuous Opioids and/or Midazolam During Early Mechanical Ventilation with Survival and Sensorimotor Outcomes at Age 2 Years in Premature Infants: Results from the French Prospective National EPIPAGE 2 Cohort.

OBJECTIVE: To evaluate the association of early continuous infusions of opioids and/or midazolam with survival and sensorimotor outcomes at age 2 years in very premature infants who were ventilated. STUDY DESIGN: This national observational study included premature infants born before 32 weeks of gestation intubated within 1 hour after birth and still intubated at 24 hours from the French EPIPAGE 2 cohort. Infants only treated with bolus were excluded. Treated infants received continuous opioid and/or midazolam infusion started before 7 days of life and before the first extubation. Naive infants did not receive these treatments before the first extubation, or received them after the first week of life, or never received them. This study compared treated (n = 450) vs naive (n = 472) infants by using inverse probability of treatment weighting after multiple imputation in chained equations. The primary outcomes were survival and survival without moderate or severe neuromotor or sensory impairment at age 2 years. RESULTS: Survival at age 2 years was significantly higher in the treated group (92.5% vs 87.9%, risk difference, 4.7%; 95% CI, 0.3-9.1; P = .037), but treated and naive infants did not significantly differ for survival without moderate or severe neuromotor or sensory impairment (86.6% vs 81.3%; risk difference, 5.3%; 95% CI -0.3 to 11.0; P = .063). These results were confirmed by sensitivity analyses using 5 alternative models. CONCLUSIONS: Continuous opioid and/or midazolam infusions in very premature infants during initial mechanical ventilation that continued past 24 hours of life were associated with improved survival without any difference in moderate or severe sensorimotor impairments at age 2 years.

Emotional responses of parents participating for the first time in caregiving for their baby in a neonatal unit.

BACKGROUND: Parents of term and preterm infants hospitalised at birth experience a stressful situation. They are considered as primary caregivers in neonatal units and are encouraged to participate in their child's care. OBJECTIVES: The aim of our study was to analyse the feelings of parents participating for the first time in caregiving for their baby admitted at birth in a neonatal unit in France and to compare the feelings reported by parents of term and preterm infants. METHODS: An online survey was created in 2014 for parents who had a baby hospitalised at birth. We analysed parents' responses to this open-ended question: "How did you feel when you participated in caregiving for your baby for the first time?" using a qualitative discourse analysis by two analysts. Themes were identified and coded. RESULTS: Between February 2014 and March 2018, 1603 parents of preterm infants and 239 parents of term infants responded to this open-ended question. Twenty-five per cent of parents expressed positive feelings exclusively (confidence, ease, joy, pride, feeling supported by healthcare professionals, by their family and feeling of being a parent), 41% expressed negative feelings exclusively (stress, fear, feeling of being judged, frustration, anger, uselessness and clumsiness) and 34% expressed mixed feelings (both positive and negative). Parents of term infants expressed less frequent feelings of stress and fear than parents of preterm infants: with a relative risk (RR) of 0.69, 95% confidence interval (CI) 0.56, 0.87. Parents of term babies more frequently expressed feelings of frustration: RR 2.40 (95% CI 1.33, 4.32). CONCLUSIONS: Infant- and Family-Centred Developmental Care supportive programmes are recommended within neonatal units in order to improve the experience of parents participating in caregiving for their baby hospitalised at birth.

Systematic review shows the benefits of involving the fathers of preterm infants in early interventions in neonatal intensive care units.

AIM: This review identifies interventions involving the fathers of preterm infants that have been tested in neonatal intensive care units (NICU). It examines their effects on the fathers and infants and highlights any differences between fathers and mothers who took part in the same interventions. METHODS: A systematic search was performed in English from 1995 to 1 September 2020, using the CINAHL, Cochrane Central Register of Controlled Trials, Embase, PubMed and PsycINFO databases. We examined 14 peer-reviewed studies that investigated NICU interventions involving 478 fathers, whose 511 infants were born before 37 weeks of gestation. These included empirical studies with clinical outcomes. RESULTS: Studies on fathers' interventions in NICUs were limited and mainly restricted to basic skin-to-skin contact or tactile interventions. The interventions had similar general positive effects on mothers and fathers when it came to infant physiological and behavioural reactions. There was also evidence of a positive effect on the fathers, including their mental health. CONCLUSION: Including fathers as active partners in the care of their preterm newborn infants produced good outcomes for both of them. Further research is needed to develop new, multimodal and interactive interventions that provide fathers with positive contact with their preterm infants.

Very preterm infants displayed similar imitation skills to full-term infants at term equivalent age.

AIM: Very preterm infants are exposed to an atypical environment that could alter their developmental trajectory. We aimed to examine neonatal imitation, a foundation of social cognition, in very preterm and full-term infants. METHODS: In Strasbourg, France, between 2015 and 2018, we prospectively investigated the development of imitation skills. Very preterm (27 to 33 weeks of gestational age, n = 20) and full-term infants (n = 20) were enrolled using four gestures: tongue protrusion, mouth opening, sequential finger movements and hand movements. All testing were performed in infants at term-equivalent age. Two independent and blinded observers coded the behaviour of each infant on video recording. Facial expressions or hand movements, similar to the one presented, were quantified and classified according to their timing. RESULTS: A total of 37 out of 40 infants imitated at least one gesture. The very preterm and term infants did not differ in the presence of imitation or its timing for the four gestures tested. The very preterm infants displayed more imitation abilities for sequential finger movement. Tongue protrusion and sequential finger movement were the particularly strong imitated gesture in both groups. CONCLUSION: These findings are the first to show similar neonatal imitation in term and very preterm infants. Our results may support early parent-infant social interactions.

Coronavirus disease 2019 in pregnancy was associated with maternal morbidity and preterm birth.

BACKGROUND: Despite the mainly reassuring outcomes for pregnant women with coronavirus disease 2019 reported by previous case series with small sample sizes, some recent reports of severe maternal morbidity requiring intubation and of maternal deaths show the need for additional data about the impact of coronavirus disease 2019 on pregnancy outcomes. OBJECTIVE: This study aimed to report the maternal characteristics and clinical outcomes of pregnant women with coronavirus disease 2019. STUDY DESIGN: This retrospective, single-center study includes all consecutive pregnant women with confirmed (laboratory-confirmed) or suspected (according to the Chinese management guideline [version 7.0]) coronavirus disease 2019, regardless of gestational age at diagnosis, admitted to the Strasbourg University Hospital (France) from March 1, 2020, to April 3, 2020. Maternal characteristics, laboratory and imaging findings, and maternal and neonatal outcomes were extracted from medical records. RESULTS: The study includes 54 pregnant women with confirmed (n=38) and suspected (n=16) coronavirus disease 2019. Of these, 32 had an ongoing pregnancy, 1 had a miscarriage, and 21 had live births: 12 vaginal and 9 cesarean deliveries. Among the women who gave birth, preterm deliveries were medically indicated for their coronavirus disease 2019-related condition for 5 of 21 women (23.8%): 3 (14.3%) before 32 weeks' gestation and 2 (9.5%) before 28 weeks' gestation. Oxygen support was required for 13 of 54 women (24.1%), including high-flow oxygen (n=2), noninvasive (n=1) and invasive (n=3) mechanical ventilation, and extracorporeal membrane oxygenation (n=1). Of these, 3, aged 35 years or older with positive test result for severe acute respiratory syndrome coronavirus 2 using reverse transcription polymerase chain reaction, had respiratory failure requiring indicated delivery before 29 weeks' gestation. All 3 women were overweight or obese, and 2 had an additional comorbidity. CONCLUSION: Coronavirus disease 2019 in pregnancy was associated with maternal morbidity and preterm birth. Its association with other well-known risk factors for severe maternal morbidity in pregnant women with no infection, including maternal age above 35 years, overweight, and obesity, suggests further studies are required to determine whether these risk factors are also associated with poorer maternal outcome in these women.

Early vocal contact and music in the NICU: new insights into preventive interventions.

It is now clearly established that the environment and the sensory stimuli, particularly during the perinatal period, have an impact on infant's development. During the last trimester of gestation, activity-dependent plasticity shapes the fetal brain, and prematurity has been shown to alter the typical developmental trajectories. In this delicate period, preventive interventions aiming at modulating these developmental trajectories through activity-inducing interventions are currently underway to be tested. The purpose of this review paper is to describe the potentialities of early vocal contact and music on the preterm infant's brain development, and their potential beneficial effect on early development. Scientific evidence supports a behavioral orientation of the newborn to organized sounds, such as those of voice and music, and recent neuroimaging studies further confirm full cerebral processing of music as multisensory stimuli. However, the impact of long-term effects of music exposure and early vocal contact on preterm infants' long-term neurodevelopment needs be further investigated. To conclude, it is necessary to establish the neuroscientific bases of the early perception and the long-term effects of music and early vocal contact on the premature newborns' development. Scientific projects are currently on the way to fill this gap in knowledge.

Perceived maternal information on premature infant's pain during hospitalization: the French EPIPAGE-2 national cohort study.

BACKGROUND: Parents of preterm neonates wish greater involvement in pain management; little is known about factors associated with this involvement. We aim to describe perceived maternal information on infants' pain during hospitalization (PMIP), to study associations between PMIP and mothers' attitudes during painful procedures, and to identify individual and contextual factors associated with PMIP. METHODS: Analyses of questionnaires from the French national cohort study of preterm neonates, EPIPAGE-2. PMIP was derived from mothers' answers to questions about information perceived on both pain assessment and management. RESULTS: Among 3056 eligible neonates born before 32 weeks, 1974, with available maternal reports, were included in the study. PMIP was classified as "sufficient," "little, not sufficient," or "insufficient, or none" for 22.7, 45.9, and 31.3% of neonates, respectively. Mothers reporting PMIP as "sufficient" were more frequently present and more likely comforting their child during painful procedures. Factors independently associated with "sufficient" PMIP were high maternal education, gestational age <29 weeks, daily maternal visits, perception of high team support, and implementation of the neonatal and individualized developmental care and assessment program. CONCLUSION: Perceived maternal information on premature infants' pain reported as sufficient increased maternal involvement during painful procedures and was associated with some units' policies.

Is laterality of congenital diaphragmatic hernia a reliable prognostic factor? French national cohort study.

OBJECTIVES: The objective of this study was to assess whether the laterality of congenital diaphragmatic hernia (CDH) was a prognostic factor for neonatal survival. METHODS: This was a cohort study using the French national database of the Reference Center for Diaphragmatic Hernias. The principal endpoint was survival after hospitalization in intensive care. We made a comparative study between right CDH and left CDH by univariate and multivariate analysis. Terminations and stillbirths were excluded from analyses of neonatal outcomes. RESULTS: A total of 506 CDH were included with 67 (13%) right CDH and 439 left CDH (87%). Rate of survival was 49% for right CDH and 74% for left CDH (P < .01). Multivariate analysis showed two factors significantly associated with mortality: thoracic herniation of liver (OR 2.27; IC 95% [1.07-4.76]; P = .03) and lung-to-head-ratio over under expected (OR 2.99; IC 95% [1.41-6.36]; P < .01). Side of CDH was not significantly associated with mortality (OR 1.87; IC 95% [0.61-5.51], P = .26). CONCLUSION: Rate of right CDH mortality is more important than left CDH. Nevertheless after adjusting for lung-to-head-ratio and thoracic herniation of liver, right CDH does not have a higher risk of mortality than left CDH.

Promoting attachment between parents and neonates despite the COVID-19 pandemic.

Social distancing is the only option available during the COVID-19 pandemic until a vaccine is developed. However, this is having a major impact on human relationships and bonding between parents and neonates is a major concern. Separation during this health emergency could have lifelong consequences for offspring, and there are even greater concerns if newborn infants are sick or vulnerable and need intensive care. We look at how bonding can be safely supported and maintained without risking infecting neonates, by comparing the international guidelines and proposing safe actions within those frameworks.

Neonatal cortical perceptions of maternal breast odours: A fNIRS study.

AIM: The aim was to determine whether preterm and full-term newborn infants could process maternal breast odour at a cortical level. METHODS: Newborn infants were exposed to cloths containing their own mother's breast odour and freshly laundered control cloths for 10 seconds, while functional near-infrared spectroscopy measured cortical activation in their olfactory processing areas. We studied 45 newborn infants born at 28-41 weeks of gestation and divided them into three groups: full-term (37-41 weeks), late preterm (33-36 weeks) and very preterm (28-32 weeks). Cortical activation was defined as a regional increase of oxyhaemoglobin following maternal breast odour stimuli. RESULTS: Full-term infants demonstrated bilateral activation of their olfactory cortices following exposure to maternal breast odour. Late preterm infants and very preterm boys exhibited unilateral cortical activation, unlike very preterm girls. CONCLUSION: Infants born from 32 weeks, and possibly earlier, could process low concentration maternal odours at a cortical level, which suggests they were more aware of their environment. These findings could make a significant contribution to improving the sensory environment of preterm infants and improve bonding.

Recommendations on neonatal light environment from the French Neonatal Society.

AIM: Hospital light may affect neonatal neurosensory development and the well-being of parents and caregivers. We aimed to issue practical recommendations regarding the optimal light environment for neonatal units. METHODS: A systematic evaluation was performed using PubMed to identify relevant papers published in English or French up to July 2018, and the different grades of evidence were evaluated. RESULTS: We identified 89 studies and one meta-analysis and examined 31 eligible studies. The major results were that natural or artificial light should not exceed 1000 lux and that all changes in light level should be gradual. Light protection should be used for infants of <32 weeks of postmenstrual age and but must be individualised to each infant. Infants should not be exposed to continuous high light levels regardless of their term and postnatal age. Cycled light before discharge seemed to be safe and beneficial. For medical caregivers' well-being, higher light levels and access to natural light are recommended. Special attention should be given to protecting neonatal patients from high light levels that may be necessary when performing specific care procedures. CONCLUSION: Consideration of general principles and practical applications can improve the neonatal light environment for newborn infants, parents and caregivers.

Cortical Responses to Alien Odors in Newborns: An fNIRS Study.

Very preterm (VPT) infants are exposed to odors released by healthcare products, triggering the trigeminal and olfactory subsystems. Irritation of the nasal mucosa induces pain in adults. We examined whether preterm and full-term (FT) newborns perceived trigeminal odors at different cortical levels, whether these odors elicit pain, and if oral glucose modulates this pain. We performed 44 recording sessions in newborn (15 VPT infants, 12 VPT infants at term-equivalent age, and 17 FT infants) following exposure to trigeminal/olfactory stimuli from the hospital environment. We repeated the exposure after oral glucose administration. We recorded cortical activation in the olfactory, frontal, and somatosensory cortices by functional near-infrared spectroscopy, and analyzed pain behaviors from videotaped recordings. Newborns integrated trigeminal/olfactory stimuli in trigeminal/olfactory and nociceptive processing areas beginning at 31 weeks postmenstrual age, and also exhibited pain behaviors. Pain scores were positively associated with the level of cortical activation. Oral glucose inhibited pain behaviors and cortical activation. There were developmental differences in cortical integration related to brain maturation and duration of the extra-uterine experience. In conclusion, VPT and FT infants showed trigeminal sensitivity after exposure to alien odors that induce pain, potentially affecting the wiring of the neuronal circuits of the newborn brain.

Recommendations on the environment for hospitalised newborn infants from the French neonatal society: rationale, methods and first recommendation on neonatal intensive care unit design.

AIM: Hospitalised newborn infants may be stressed due to inappropriate sensory stimuli and early separation from their families, that can negatively impact their neurodevelopment. The French Group of Reflection and Evaluation of the Environment of Newborns (GREEN) issues guidelines based on environmental neonatology and family-centred care. The first recommendation focuses on private family rooms versus large shared rooms. METHODS: These guidelines are based on a systematic evaluation of the literature providing different grades of evidence. Internal and external reviews by multidisciplinary experts examined the scientific evidence of all recommendations. The literature search was performed for the period January 1, 2000 to January 1, 2016 with the keywords 'single room' or 'private room' and 'neonatal intensive care unit'. RESULTS: A total of 25 studies were retained. Most studies reported a positive impact of private rooms on the health of newborn infants and satisfaction of families. Private rooms could lead to sensory deprivation if there is low parental involvement with limited presence and to reduced interaction among caregivers. CONCLUSION: We recommend that neonatal units should mostly have private rooms. With this architectural design, we recommend supporting the staff's needs for changes in the organisation and philosophy of care and to provide improved family support.