Impact of an integrated health, nutrition, and early child stimulation and responsive care intervention package delivered to preterm or term small for gestational age babies during infancy on growth and neurodevelopment: study protocol of an individually randomized controlled trial in India (Small Babies Trial).

BACKGROUND: Preterm and term small for gestational age (SGA) babies are at high risk of experiencing malnutrition and impaired neurodevelopment. Standalone interventions have modest and sometimes inconsistent effects on growth and neurodevelopment in these babies. For greater impact, intervention may be needed in multiple domains-health, nutrition, and psychosocial care and support. Therefore, the combined effects of an integrated intervention package for preterm and term SGA on growth and neurodevelopment are worth investigating. METHODS: An individually randomized controlled trial is being conducted in urban and peri-urban low to middle-socioeconomic neighborhoods in South Delhi, India. Infants are randomized (1:1) into two strata of 1300 preterm and 1300 term SGA infants each to receive the intervention package or routine care. Infants will be followed until 12 months of age. Outcome data will be collected by an independent outcome ascertainment team at infant ages 1, 3, 6, 9, and 12 months and at 2, 6, and 12 months after delivery for mothers. DISCUSSION: The findings of this study will indicate whether providing an intervention that addresses factors known to limit growth and neurodevelopment can offer substantial benefits to preterm or term SGA infants. The results from this study will increase our understanding of growth and development and guide the design of public health programs in low- and middle-income settings for vulnerable infants. TRIAL REGISTRATION: The trial has been registered prospectively in Clinical Trial Registry - India # CTRI/2021/11/037881, Registered on 08 November 2021.

Calcium and Phosphorus: All You Need to Know but Were Afraid to Ask.

Inadequate intake of calcium and phosphorus during the perinatal period can result in metabolic bone disease (MBD), characterized by decreased bone mass, altered bone mineralization, and increased risk for fractures. Preterm neonates have higher risk of developing MBD. Treating MBD involves ensuring adequate calcium and phosphorus intake, early fortification, and vitamin D supplementation. Health care providers should closely monitor nutrient intake, postnatal growth, and screening of preterm neonates at risk for MBD. This review summarizes the critical roles of calcium and phosphorus in regulating bone physiology, how they regulate bone formation and resorption, and their influence on overall bone health.

Correlation between diminished vagal tone and somatic dysfunction severity in very and extremely low birth weight preterm infants assessed with frequency spectrum heart rate variability and salivary cortisol.

Osteopathic manipulative treatment (OMT) is evolving in the neonatal intensive care unit (NICU) setting. Studies showed its efficacy in length of stay and hospitalization costs reduction. Moreover, it was suggested that OMT has a modulatory effect on the preterm infants' autonomic nervous system (ANS), influencing saturation and heart rate. Even if OMT is based on the palpatory examination of the somatic dysfunctions (SD), there are controversies about its identification and clinical relevance. The objective of this study was to evaluate the inter-rater reliability, clinical characteristics, and functional correlation of the SD Grade score with the heart rate variability (HRV) and the salivary cortisol (sCor) using a multivariate linear model approach. To evaluate those features, we implemented an ad hoc SD examination for preterm infants that was performed by 2 trained osteopaths. It was based on the new variability model of SD that includes an SD Grade assessment procedure. The ANS features were assessed by frequency parameters of HRV studying high frequency (HF), low frequency (LF), and HF/LF, whereas sCor was tested with a radioimmunoassay. The ANS assessment was standardized and performed before SD testing. Sixty-nine premature infants were eligible. SD Grade showed excellent concordance between the blinded raters. Using SD Grade as a grouping variable, the infants presented differences in GA, Apgar, pathological findings, length of stay, and ventilatory assistance. In our multivariate model, HF, LF, and LF/HF resulted linearly correlated with SD Grade. Instead, sCor presented a linear correlation with 5' Apgar and respiratory distress syndrome but not with SD Grade. SD Grade was in line with the natural history of the underdevelopment due to prematurity. Our models indicate that the cardiac vagal tone is linearly related with SD Grade. This finding may improve the multidisciplinary decision making inside NICU and the management of modifiable factors, like SD, for cardiac vagal tone regulation.

Effect of Music Therapy Interventions on Heart Rate Variability in Premature Infants.

Premature infants are at risk of developing serious complications after birth. Communicative interventions performed in neonatal intensive care units (NICUs), such as music therapy interventions, can reduce the stress experienced by these infants and promote the development of their autonomic nervous system. In this study we investigated the effects of music therapy interventions, consisting of singing, humming, talking or rhythmic reading, on premature infants by investigating the effects on their heart rate variability (HRV). A total of 27 communicative intervention from 18 patients were included in this study. The NN-intervals were extracted from the ECG and the mean ± SEM values for the 6 different features (HR, SDNN, RMSSD, pNN50, pDec and SDDec) was investigated. Median feature values for the pre- and communicative intervention were compared using the Wilcoxon signed-rank test. An increase in values for the SDNN, RMSSD and pNN50 was found in the 20 minutes preceding the communicative intervention, when caregiving activities were performed, and was followed by an immediate decrease at the start of the intervention. Features' variability during the intervention appeared to be smaller than in the pre-communicative intervention, indicating improved autonomic regulation. This difference was, however, not statistically significant possibly due to different types of activities applied during the communicative intervention per patient.

Short-term Music Therapy for Families With Preterm Infants: A Randomized Trial.

OBJECTIVES: To evaluate short-term effects of music therapy (MT) for premature infants and their caregivers on mother-infant bonding, parental anxiety, and maternal depression. METHODS: Parallel, pragmatic, randomized controlled-trial conducted in 7 level III NICUs and 1 level IV NICU in 5 countries enrolling premature infants (<35 weeks gestational age at birth) and their parents. MT included 3 sessions per week with parent-led, infant-directed singing supported by a music therapist. Primary outcome was mother-infant bonding as measured by the Postpartum Bonding Questionnaire (PBQ) at discharge from NICU. Secondary outcomes were parents' symptoms of anxiety measured by General Anxiety Disorder-7 (GAD-7) and maternal depression measured by Edinburgh Postpartum Depression Scale (EPDS). Group differences at the assessment timepoint of discharge from hospital were tested by linear mixed effect models (ANCOVA). RESULTS: From August 2018 to April 2020, 213 families were enrolled in the study, of whom 108 were randomly assigned to standard care and 105 to MT. Of the participants, 208 of 213 (98%) completed treatment and assessments. Participants in the MT group received a mean (SD) of 10 sessions (5.95), and 87 of 105 participants (83%) received the minimum of 6 sessions. The estimated group effect (95% confidence interval) for PBQ was -0.61 (-1.82 to 0.59). No significant differences between groups were found (P = .32). No significant effects for secondary outcomes or subgroups were found. CONCLUSIONS: Parent-led, infant-directed singing supported by a music therapist resulted in no significant differences between groups in mother-infant bonding, parental anxiety, or maternal depression at discharge.

Musical memories in newborns: A resting-state functional connectivity study.

Music is known to induce emotions and activate associated memories, including musical memories. In adults, it is well known that music activates both working memory and limbic networks. We have recently discovered that as early as during the newborn period, familiar music is processed differently from unfamiliar music. The present study evaluates music listening effects at the brain level in newborns, by exploring the impact of familiar or first-time music listening on the subsequent resting-state functional connectivity in the brain. Using a connectome-based framework, we describe resting-state functional connectivity (RS-FC) modulation after music listening in three groups of newborn infants, in preterm infants exposed to music during their neonatal-intensive-care-unit (NICU) stay, in control preterm, and full-term infants. We observed modulation of the RS-FC between brain regions known to be implicated in music and emotions processing, immediately following music listening in all newborn infants. In the music exposed group, we found increased RS-FC between brain regions known to be implicated in familiar and emotionally arousing music and multisensory processing, and therefore implying memory retrieval and associative memory. We demonstrate a positive correlation between the occurrence of the prior music exposure and increased RS-FC in brain regions implicated in multisensory and emotional processing, indicating strong engagement of musical memories; and a negative correlation with the Default Mode Network, indicating disengagement due to the aforementioned cognitive processing. Our results describe the modulatory effect of music listening on brain RS-FC that can be linked to brain correlates of musical memory engrams in preterm infants.

Clinical benefits of music-based interventions on preterm infants' health: A systematic review of randomised trials.

AIM: This systematic review aimed to differentiate and isolate the results of different music-based interventions used with preterm infants in the neonatal intensive care unit and explore their clinical benefits. METHODS: The last search was performed on 5 July 2021 on Web of Science, Scopus, EMBASE, PsycINFO, CINAHL, LILACS and CENTRAL. Only randomised clinical trials that explored the health benefits of music-based interventions were considered. RESULTS: A total of 39 studies were included. All music-based interventions were divided into music medicine and music therapy. The overall results suggested that music medicine interventions were associated with a significant improvement in pain relief; in turn, improvements in cardiac and respiratory function, weight gain, eating behaviour, and quiet alert and sleep states were more consistent in studies that followed a music therapy approach with the presence of a music therapist. CONCLUSION: This review supports the beneficial effects of music-based interventions on the health of preterm infants in a neonatal intensive care unit; however, it also offers suggestions for future studies in order to increase the number of interventions with music therapists, since the results of music therapy approaches were more consistent for physiological and behavioural outcomes.

A Mixed-Lipid Emulsion Containing Fish Oil for the Parenteral Nutrition of Preterm Infants: No Impact on Visual Neuronal Conduction.

Fish oil is rich in omega-3 fatty acids and essential for neuronal myelination and maturation. The aim of this study was to investigate whether the use of a mixed-lipid emulsion composed of soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF-LE) compared to a pure soybean oil-based lipid emulsion (S-LE) for parenteral nutrition had an impact on neuronal conduction in preterm infants. This study is a retrospective matched cohort study comparing preterm infants <1000 g who received SMOF-LE in comparison to S-LE for parenteral nutrition. Visual evoked potentials (VEPs) were assessed longitudinally from birth until discharge. The latencies of the evoked peaks N2 and P2 were analyzed. The analysis included 76 infants (SMOF-LE: n = 41 and S-LE: n = 35) with 344 VEP measurements (SMOF-LE: n= 191 and S-LE n = 153). Values of N2 and P2 were not significantly different between the SMOF-LE and S-LE groups. A possible better treatment effect in the SMOF-LE group was seen as a trend toward a shorter latency, indicating faster neural conduction at around term-equivalent age. Prospective trials and follow-up studies are necessary in order to evaluate the potential positive effect of SMOF-LE on neuronal conduction and visual pathway maturation.

Association of Docosahexaenoic Acid and Arachidonic Acid Serum Levels With Retinopathy of Prematurity in Preterm Infants.

Importance: Supplementing preterm infants with long-chain polyunsaturated fatty acids (LC-PUFA) has been inconsistent in reducing the severity and incidence of retinopathy of prematurity (ROP). Furthermore, few studies have measured the long-term serum lipid levels after supplementation. Objective: To assess whether ROP severity is associated with serum levels of LC-PUFA, especially docosahexaenoic acid (DHA) and arachidonic acid (AA), during the first 28 postnatal days. Design, Setting, and Participants: This cohort study analyzed the Mega Donna Mega study, a randomized clinical trial that provided enteral fatty acid supplementation at 3 neonatal intensive care units in Sweden. Infants included in this cohort study were born at a gestational age of less than 28 weeks between December 20, 2016, and August 6, 2019. Main Outcomes and Measures: Severity of ROP was classified as no ROP, mild or moderate ROP (stage 1-2), or severe ROP (stage 3 and type 1). Serum phospholipid fatty acids were measured through gas chromatography-mass spectrometry. Ordinal logistic regression, with a description of unadjusted odds ratio (OR) as well as gestational age- and birth weight-adjusted ORs and 95% CIs, was used. Areas under the curve were used to calculate mean daily levels of fatty acids during postnatal days 1 to 28. Blood samples were obtained at the postnatal ages of 1, 3, 7, 14, and 28 days. Results: A total of 175 infants were included in analysis. Of these infants, 99 were boys (56.6%); the median (IQR) gestational age was 25 weeks 5 days (24 weeks 3 days to 26 weeks 6 days), and the median (IQR) birth weight was 785 (650-945) grams. A higher DHA proportion was seen in infants with no ROP compared with those with mild or moderate ROP or severe ROP (OR per 0.5-molar percentage increase, 0.49 [95% CI, 0.36-0.68]; gestational age- and birth weight-adjusted OR, 0.66 [95% CI, 0.46-0.93]). The corresponding adjusted OR for AA levels per 1-molar percentage increase was 0.83 (95% CI, 0.66-1.05). The association between DHA levels and ROP severity appeared only in infants with sufficient AA levels, suggesting that a mean daily minimum level of 7.8 to 8.3 molar percentage of AA was necessary for a detectable association between DHA level and less severe ROP. Conclusions and Relevance: This cohort study found that higher mean daily serum levels of DHA during the first 28 postnatal days were associated with less severe ROP even after adjustment for known risk factors, but only in infants with sufficiently high AA levels. Further studies are needed to identify LC-PUFA supplementation strategies that may prevent ROP and other morbidities.

Effect of non-pharmacological interventions on sleep in preterm infants in the neonatal intensive care unit: A protocol for systematic review and network meta-analysis.

BACKGROUND: Premature infants are prone to suffer multisystem complications after birth due to the incomplete development of organ tissues and low immunity, and they require a longer period of supervised treatment in the neonatal intensive care unit (NICU). However, due to the specificity of medical care in the NICU, the sleep of preterm infants is highly susceptible that has an impact on the prognosis of preterm infants. Recently, various non-pharmacological interventions have been applied to the sleep of preterm infants in the NICU, which have shown positive outcomes. However, the efficacy and safety of them are unclear. This study aims to evaluate the effects of non-pharmacological interventions on sleep in preterm infants in the NICU through a network meta-analysis. METHODS: Randomized controlled trials of non-pharmacological interventions on sleep in preterm infants in the NICU published before September 2021 will be searched in online databases, including the Chinese Scientific Journal Database, China National Knowledge Infrastructure Database, Wanfang, China Biomedical Literature Database, PubMed, Cochrane Library, Embase, and Web of Science. Two researchers will be independently responsible for screening and selecting eligible literatures, extracting data and evaluating the risk of bias in the included studies. Stata 14.0 software will be used for data analysis. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will provide comprehensive and reliable evidence-based references for the efficacy and safety in different non-pharmacological interventions on sleep in preterm infants in the NICU.

Administration of parenteral nutrition during therapeutic hypothermia: a population level observational study using routinely collected data held in the National Neonatal Research Database.

BACKGROUND: Parenteral nutrition is commonly administered during therapeutic hypothermia. Randomised trials in critically ill children indicate that parenteral nutrition may be harmful. OBJECTIVE: To examine the association between parenteral nutrition during therapeutic hypothermia and clinically important outcomes. DESIGN: Retrospective, population-based cohort study using the National Neonatal Research Database; propensity scores were used to create matched groups for comparison. SETTING: National Health Service neonatal units in England, Scotland and Wales. PARTICIPANTS: 6030 term and near-term babies, born 1/1/2010 and 31/12/2017, who received therapeutic hypothermia; 2480 babies in the matched analysis. EXPOSURE: We compared babies that received any parenteral nutrition during therapeutic hypothermia with babies that did not. MAIN OUTCOME MEASURES: Primary outcome: blood culture confirmed late-onset infection; secondary outcomes: treatment for late onset infection, necrotising enterocolitis, survival, length of stay, measures of breast feeding, hypoglycaemia, central line days, time to full enteral feeds, discharge weight. RESULTS: 1475/6030 babies (25%) received parenteral nutrition. In comparative matched analyses, the rate of culture positive late onset infection was higher in babies that received parenteral nutrition (0.3% vs 0.9%; difference 0.6; 95% CI 0.1, 1.2; p=0.03), but treatment for presumed infection was not (difference 0.8%, 95% CI -2.1 to 3.6, p=0.61). Survival was higher in babies that received parenteral nutrition (93.1% vs 90.0%; rate difference 3.1, 95% CI 1.5, 4.7; p<0.001). CONCLUSIONS: Receipt of parenteral nutrition during therapeutic hypothermia is associated with higher late-onset infection but lower mortality. This finding may be explained by residual confounding. Research should address the risks and benefits of parenteral nutrition in this population.

Comparing the effectiveness of mother's live lullaby and recorded lullaby on physiological responses and sleep of preterm infants: a clinical trial study.

OBJECTIVES: Environmental stimuli in neonatal intensive care units can disrupt the physiological stability and sleep of infants. It is essential to perform nursing interventions to reduce the adverse effects of such stimuli. This study aimed to compare the effect of recorded lullabies and mothers' live lullabies on physiological responses and sleep duration of preterm infants. METHODS: This study was a randomized clinical trial. The participants were 90 preterm infants selected using convenience sampling. In the intervention groups, music (recorded lullabies and mother's live lullabies) was played for 14 days, 20 min a day, while the control group did not receive any intervention. The data were collected using physiological criteria and infant sleep checklists before, during, and after the intervention. The data were analyzed using SPSS software (Version 21.0). RESULTS: The mean scores of physiological parameters (O2 saturation and heart rate) were not significantly different in the three groups before, during, and after the intervention (p>0.05). However, there was an improvement in O2-saturation and a decrease in the heart rate in two intervention groups. The mean duration of the infants' overnight sleep was not statistically significant between the groups before the intervention (p>0.05). However, there was a statistically significant difference in the intervention groups after the intervention, (p<0.05), and the infants' overnight sleep was longer in the recorded-lullaby group than the other two groups. CONCLUSIONS: Although performing interventions, including recorded lullaby and mother's live lullaby did not differ significantly with that of the control group in physiological criteria, it can be clinically important. In addition, recorded-lullaby increased the infants' overnight sleeping. Thus, it is suggested that further studies be conducted to confirm the effect of recorded lullaby and mother's live lullaby interventions on physiological parameters and sleep duration of hospitalized infants.

Early protein intake predicts functional connectivity and neurocognition in preterm born children.

Nutritional intake can promote early neonatal brain development in very preterm born neonates (< 32 weeks' gestation). In a group of 7-year-old very preterm born children followed since birth, we examined whether early nutrient intake in the first weeks of life would be associated with long-term brain function and neurocognitive skills at school age. Children underwent resting-state functional MRI (fMRI), intelligence testing (Wechsler Intelligence Scale for Children, 5th Ed) and visual-motor processing (Beery-Buktenica, 5th Ed) at 7 years. Relationships were assessed between neonatal macronutrient intakes, functional connectivity strength between thalamic and default mode networks (DMN), and neuro-cognitive function using multivariable regression. Greater functional connectivity strength between thalamic networks and DMN was associated with greater intake of protein in the first week (ß = 0.17; 95% CI 0.11, 0.23, p < 0.001) but lower intakes of fat (ß = - 0.06; 95% CI - 0.09, - 0.02, p = 0.001) and carbohydrates (ß = - 0.03; 95% CI - 0.04, - 0.01, p = 0.003). Connectivity strength was also associated with protein intake during the first month (ß = 0.22; 95% CI 0.06, 0.37, p = 0.006). Importantly, greater thalamic-DMN connectivity strength was associated with higher processing speed indices (ß = 26.9; 95% CI 4.21, 49.49, p = 0.02) and visual processing scores (ß = 9.03; 95% CI 2.27, 15.79, p = 0.009). Optimizing early protein intake may contribute to promoting long-term brain health in preterm-born children.

Pain Control with Lavender Oil in Premature Infants: A Double-Blind Randomized Controlled Study.

Objectives: Aromatherapy has become popular in pain control in recent years compared with other complementary methods. Lavender (Lavandula angustifolia Miller) is a fragrant essential oil used in aromatherapy for its antibacterial, antifungal, muscle-relaxing, and analgesic effects. The smell of lavender oil, known for its soothing effect on adults, has not been adequately investigated in regards to pain control in premature infants. The purpose of our study was to assign the effect of the scent of lavender oil on pain in preterm infants during heel lancing. Design: A double-blind randomized controlled clinical study. Settings/Location: The study was conducted in a third-level neonatal intensive care unit of Bezmialem Vakif University Hospital from March 2019 to November 2019. It consisted of two groups. Subjects: Sixty-one premature babies (24-37 weeks of gestation) were enrolled in the study. Interventions: Heel stick sampling for metabolic screening was used for both study groups. The interventions were performed by two experienced nurses. Heart rate, oxygen saturation, and the baby's facial expression were recorded by a camera 3 min before the intervention, during the sampling, and 3 min after the procedure. After collecting the data, the head researcher and the assistant researcher separately watched the videos and scored them by using the Premature Infant Pain Profile-Revised (PIPP-R). Outcome measures: The difference of pain scores (PIIP-R) between two groups. Results: There was a statistically significant difference between the two groups in terms of PIPP-R scores during and after the sampling (p = 0.008 and p = 0.03 respectively). The PIPP-R scores at the beginning of the procedure were not found to be significantly different between the groups (p > 0.05). Conclusions: Inhalation of lavender scent is effective in pain control in premature infants. It is safe and low cost; it does not interfere with medical care.

Microbiota Supplementation with Bifidobacterium and Lactobacillus Modifies the Preterm Infant Gut Microbiota and Metabolome: An Observational Study.

Supplementation with members of the early-life microbiota as "probiotics" is increasingly used in attempts to beneficially manipulate the preterm infant gut microbiota. We performed a large observational longitudinal study comprising two preterm groups: 101 infants orally supplemented with Bifidobacterium and Lactobacillus (Bif/Lacto) and 133 infants non-supplemented (control) matched by age, sex, and delivery method. 16S rRNA gene profiling on fecal samples (n = 592) showed a predominance of Bifidobacterium and a lower abundance of pathobionts in the Bif/Lacto group. Metabolomic analysis showed higher fecal acetate and lactate and a lower fecal pH in the Bif/Lacto group compared to the control group. Fecal acetate positively correlated with relative abundance of Bifidobacterium, consistent with the ability of the supplemented Bifidobacterium strain to metabolize human milk oligosaccharides into acetate. This study demonstrates that microbiota supplementation is associated with a Bifidobacterium-dominated preterm microbiota and gastrointestinal environment more closely resembling that of full-term infants.

Effects of osteopathic treatment versus static touch on heart rate and oxygen saturation in premature babies: A randomized controlled trial.

BACKGROUND: Osteopathic manipulative treatment (OMT) has been successfully tested in the context of preterm infants. No studies, however, have been conducted to investigate the OMT immediate effects on physiological measurements, such as partial oxygen saturation (SpO2) and heart rate (HR). The purpose of the present study was to assess the effect of osteopathic treatment on SpO2 and HR values and to compare it with 10 min of static touch. MATERIALS AND METHODS: Ninety-six preterm infants (41 male), aged 33.5 weeks (±4.3) with mean weight at birth of 2067gr (±929) were recruited from the neonatal intensive care unit (NICU) of the Buzzi Hospital in Milan, and randomly allocated to two groups: OMT and Static Touch. Each protocol session consisted of: a) 5-min Pre-touch baseline recording, b) 10-min touch procedure, c) 5-min post-touch recording. Primary and secondary outcomes were, respectively, the baseline changes of HR and SpO2. RESULTS: The 2 × 2 repeated measure ANOVA for HR showed a statistically significant effect (F (1,94) = 5.34; p < 0.02), revealing that the OMT group decreases the HR value at T2 (p = 0.006). In contrast, SpO2 analysis showed an increase of SpO2 value where the OMT group demonstrated higher values at T2 (p = 0.04). CONCLUSION: Results from the present study suggest that a single osteopathic intervention may induce beneficial effects on preterm physiological parameters. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03833635 - Date: February 7, 2019.

Lactobacillus Acidophilus/Bifidobacterium Infantis Probiotics Are Beneficial to Extremely Low Gestational Age Infants Fed Human Milk.

Objective: To evaluate the nutrition-related effects of prophylactic Lactobacillus acidophilus/Bifidobacterium infantis probiotics on the outcomes of preterm infants <29 weeks of gestation that receive human milk and/or formula nutrition. We hypothesize that human-milk-fed infants benefit from probiotics in terms of sepsis prevention and growth. METHODS: We performed an observational study of the German Neonatal Network (GNN) over a period of six years, between 1 January, 2013 and 31 December, 2018. Prophylactic probiotic use of L. acidophilus/B. infantis was evaluated in preterm infants <29 weeks of gestation (n = 7516) in subgroups stratified to feeding type: (I) Exclusively human milk (HM) of own mother and/or donors (HM group, n = 1568), (II) HM of own mother and/or donor and formula (Mix group, n = 5221), and (III) exclusive exposure to formula (F group, n = 727). The effect of probiotics on general outcomes and growth was tested in univariate models and adjusted in linear/logistic regression models. RESULTS: 5954 (76.5%) infants received L. acidophilus/B. infantis prophylactically for the prevention of necrotizing enterocolitis (NEC). Probiotic use was associated with improved growth measures in the HM group (e.g., weight gain velocity in g/day: effect size B = 0.224; 95% CI: 2.82-4.35; p < 0.001) but not in the F group (effect size B = -0.06; 95% CI: -3.05-0.28; p = 0.103). The HM group had the lowest incidence of clinical sepsis (34.0%) as compared to the Mix group (35.5%) and the F group (40.0%). Only in the Mix group, probiotic supplementation proved to be protective against clinical sepsis (OR 0.69; 95% CI: 0.59-0.79; p < 0.001). CONCLUSION: Our observational data indicate that the exposure to L. acidophilus/B. infantis probiotics may promote growth in exclusively HM-fed infants as compared to formula-fed infants. To exert a sepsis-preventive effect, probiotics seem to require human milk.

Creative music therapy to promote brain function and brain structure in preterm infants: A randomized controlled pilot study.

Cognitive and neurobehavioral problems are among the most severe adverse outcomes in very preterm infants. Such neurodevelopmental impairments may be mitigated through nonpharmacological interventions such as creative music therapy (CMT), an interactive, resource- and needs-oriented approach that provides individual social contact and musical stimulation. The aim was to test the feasibility of a study investigating the role of CMT and to measure the short- and medium-term effects of CMT on structural and functional brain connectivity with MRI. In this randomized, controlled clinical pilot feasibility trial, 82 infants were randomized to either CMT or standard care. A specially trained music therapist provided CMT via infant-directed humming and singing in lullaby style. To test the short-term effects of CMT on brain structure and function, diffusion tensor imaging data and resting-state functional imaging data were acquired. Clinical feasibility was achieved despite moderate parental refusal mainly in the control group after randomization. 40 infants remained as final cohort for the MRI analysis. Structural brain connectivity appears to be moderately affected by CMT, structural connectomic analysis revealed increased integration in the posterior cingulate cortex only. Lagged resting-state MRI analysis showed lower thalamocortical processing delay, stronger functional networks, and higher functional integration in predominantly left prefrontal, supplementary motor, and inferior temporal brain regions in infants treated with CMT. This trial provides unique evidence that CMT has beneficial effects on functional brain activity and connectivity in networks underlying higher-order cognitive, socio-emotional, and motor functions in preterm infants. Our results indicate the potential of CMT to improve long-term neurodevelopmental outcomes in children born very preterm.

Evaluation of an intervention supporting breastfeeding among late-preterm infants during in-hospital stay.

BACKGROUND: Late-preterm infants show lower breastfeeding rates when compared with term infants. Current practice is to keep them in low-risk wards where clinical guidelines to support breastfeeding are well established for term infants but can be insufficient for late-preterm. OBJECTIVE: The aim of this study was to evaluate an intervention supporting breastfeeding among late-preterm infants in a maternity service in the Basque Country, Spain. METHODS: The intervention was designed to promote parents' education and involvement, provide a multidisciplinary approach and decision-making, and avoid separation of the mother-infant dyad. A quasi-experimental study was conducted with a control (n=212) and an intervention group (n=161). Data was collected from clinical records from November 2012 to January 2015. Feeding rate at discharge, breast-pump use, incidence of morbidities, infant weight loss and hospital stay length were compared between the two groups. RESULTS: Infants in the control group were 50.7% exclusive breastfeeding, 37.8% breastfeeding, and, 11.5% formula feeding at discharge, whereas in the intervention group, frequencies were 68.4%, 25.9%, and 5.7%, respectively (p=0.002). Mothers in the intervention group were 2.66 times more likely to use the breast-pump after almost all or all feeds and 2.09 times more likely to exclusively breastfeed at discharge. There were no significant differences in morbidities and infant weight loss between groups. Hospital stay was longer for infants who required phototherapy in the intervention group (p=0.009). CONCLUSION: The intervention resulted in a higher breastfeeding rate at discharge. Interventions aimed to provide specific support among late-pretem infants in maternity services are effective.

Effect of environmental music on autonomic function in infants in intensive and growing care units.

BACKGROUND: The aim of this study is (1) to observe the effect of the background music (BGM) in the incubator on heart rate variability (HRV) during the first few weeks of life in preterm infants in the neonatal intensive (NICU) and growing care units (GCU) and (2) to investigate the effect of environmental music on autonomic function in the infants. METHODS: Thirty infants, including premature (26 3/7 - 38 4/7 weeks) and low-birth weight (LBW) (946-2,440 g) infants, admitted to the NICU or GCU were involved. The heart rate, low- (LF, 0.05-0.15 Hz) and high- (HF, 0.15-0.4 Hz) frequency HRV components, and LF/HF ratio were measured. The BGM, lullabies for a baby, was delivered through a speaker in the incubator, and the HRV components were compared among before, during, and after intervention with BGM. RESULTS: The mean HR did not change among the experimental conditions. The LF and HF values decreased during the BGM condition, but not LF/HF, compared with the condition before BGM. CONCLUSIONS: The present results showed that an auditory environment affected the autonomic function of infants with a range of BGM in the NICU/GCU. The present study also suggested that BGM, a non-invasive and non-pharmacological intervention, could be an evaluation tool for autonomic function in infants in NICU/GCU.