Music therapy and weight gain in preterm infants: Secondary analysis of the randomized controlled LongSTEP trial.

OBJECTIVES: This study assessed the association between MT and weight gain among preterm infants hospitalized in Neonatal Intensive Care Units. METHODS: Data collected during the international, randomized, Longitudinal Study of Music Therapy's Effectiveness for Premature Infants and their Caregivers (LongSTEP) study were compared between the MT group and the standard care (SC) group. Weights were recorded at birth, enrollment, and discharge. Weight percentiles, Z-scores, weight gain velocity, and extrauterine growth restriction (EUGR) were calculated. RESULTS: Among 201 preterm infants included, no significant differences in weight parameters (weight, weight percentiles, weight Z-scores; all p ≥ 0.23) were found between the MT group (n = 104) and the SC (n = 97) group at birth, enrollment, or discharge. No statistical differences in EUGR represented by change in Z-scores from birth to discharge were recorded between MT and SC (0.8 vs. 0.7). Among perinatal parameters, younger gestational age (p = 0.005) and male sex (p = 0.012) were associated with increased risk of EUGR at discharge. Antenatal steroid treatment, systemic infection, bronchopulmonary dysplasia, neurological morbidities, retinopathy of prematurity, necrotizing enterocolitis, parental factors (amount of skin-to-skin care, bonding, anxiety, and depression questionnaire scores), and type of enteral nutrition did not significantly influence weight gain parameters (all p > 0.05). CONCLUSIONS: In the LongSTEP study, MT for preterm infants and families was not associated with better weight parameters compared to the SC group. The degree of prematurity remains the main risk factor for unfavorable weight parameters.

The Effect of Assisted Exercise Frequency on Bone Strength in Very Low Birth Weight Preterm Infants: A Randomized Control Trial.

We aimed to assess whether a twice daily assisted exercise interventional program will have a greater effect on bone strength compared to a once daily intervention or no intervention in very low birth weight (VLBW) preterm infants. Thirty-four very VLBW preterm infants (mean BW 1217 ± 55 g and mean gestational age 28.6 ± 1.1 weeks) were randomly assigned into one of three study groups: twice daily interventions (n = 13), a once daily intervention (n = 11), and no intervention (control, n = 10). The intervention was initiated at a mean of 8 ± 2.4 days of life and continued for 4 weeks. It included passive extension and flexion range-of-motion exercise of the upper and lower extremities. Bone strength was measured at enrollment and after 2 and 4 weeks using quantitative ultrasound of tibial bone speed of sound (SOS, Sunlight Omnisense™). At enrollment, the mean bone SOS was comparable between the twice daily interventions, once daily intervention and control groups (2918 ± 78, 2943 ± 119, and 2910 ± 48 m/s, respectively). As expected, the bone SOS declined in all groups during the study period (-23.6 ± 24, -68.8 ± 28, and -115.8 ± 30 m/s, respectively, p < 0.05), with a significantly attenuated decrease in bone strength in the twice daily intervention group (p = 0.03). A twice daily intervention program of assisted range-of-motion exercise attenuates the decrease in bone strength and may decrease the risk of osteopenia and future fractures in VLBW preterm infants.

Association between neonatal morbidities and head growth from birth until discharge in very-low-birthweight infants born preterm: a population-based study.

AIM: To evaluate the possible association between major neonatal morbidities and poor head growth from birth to discharge home in very-low-birthweight (VLBW) infants born preterm. METHOD: Population-based observational study comprising 12 992 infants (6340 male, 6652 female) of 24 to 32 weeks' gestation, and birthweight ≤1500g. Severe head growth failure (HGF) was defined as a decrease in head circumference z-score >2 z-scores, and moderate HGF as a decrease of 1 to 2 z-scores. Multinomial logistic regression analysis was applied to determine morbidities associated with HGF. RESULTS: Severe HGF occurred in 4.5% and moderate HGF in 20.9% of infants. Each unit increase in head circumference z-score at birth was associated with increased odds for severe and moderate HGF (odds ratios [OR] 5.29, 95% confidence intervals [CI] 4.67-6.00, and OR 2.38, 95% CI 2.23-2.54 respectively). Both severe and moderate HGF were associated with respiratory distress syndrome (OR 2.03, 95% CI 1.58-2.62, and OR 1.66, 95% CI 1.48-1.85 respectively); bronchopulmonary dysplasia (OR 3.38, 95% CI 2.33-4.91, and OR 1.87, 95% CI 1.52-2.30 respectively); necrotizing enterocolitis (OR 2.89, 95% CI 2.04-4.09, and OR 1.72, 95% CI 1.38-2.16 respectively), and sepsis (OR 2.06, 95% CI 1.69-2.50, and OR 1.38, 95% CI 1.24-1.53 respectively). INTERPRETATION: Major neonatal morbidities were associated with HGF in VLBW infants born preterm. Identification of whether this is a direct effect of these morbidities or mediated through nutritional or growth factors may enable interventions to improve postnatal head growth of infants born preterm.

National Rapid Genome Sequencing in Neonatal Intensive Care.

Importance: National implementation of rapid trio genome sequencing (rtGS) in a clinical acute setting is essential to ensure advanced and equitable care for ill neonates. Objective: To evaluate the feasibility, diagnostic efficacy, and clinical utility of rtGS in neonatal intensive care units (NICUs) throughout Israel. Design, Setting, and Participants: This prospective, public health care-based, multicenter cohort study was conducted from October 2021 to December 2022 with the Community Genetics Department of the Israeli Ministry of Health and all Israeli medical genetics institutes (n = 18) and NICUs (n = 25). Critically ill neonates suspected of having a genetic etiology were offered rtGS. All sequencing, analysis, and interpretation of data were performed in a central genomics center at Tel-Aviv Sourasky Medical Center. Rapid results were expected within 10 days. A secondary analysis report, issued within 60 days, focused mainly on cases with negative rapid results and actionable secondary findings. Pathogenic, likely pathogenic, and highly suspected variants of unknown significance (VUS) were reported. Main Outcomes and Measures: Diagnostic rate, including highly suspected disease-causing VUS, and turnaround time for rapid results. Clinical utility was assessed via questionnaires circulated to treating neonatologists. Results: A total of 130 neonates across Israel (70 [54%] male; 60 [46%] female) met inclusion criteria and were recruited. Mean (SD) age at enrollment was 12 (13) days. Mean (SD) turnaround time for rapid report was 7 (3) days. Diagnostic efficacy was 50% (65 of 130) for disease-causing variants, 11% (14 of 130) for VUS suspected to be causative, and 1 novel gene candidate (1%). Disease-causing variants included 12 chromosomal and 52 monogenic disorders as well as 1 neonate with uniparental disomy. Overall, the response rate for clinical utility questionnaires was 82% (107 of 130). Among respondents, genomic testing led to a change in medical management for 24 neonates (22%). Results led to immediate precision medicine for 6 of 65 diagnosed infants (9%), an additional 2 (3%) received palliative care, and 2 (3%) were transferred to nursing homes. Conclusions and Relevance: In this national cohort study, rtGS in critically ill neonates was feasible and diagnostically beneficial in a public health care setting. This study is a prerequisite for implementation of rtGS for ill neonates into routine care and may aid in design of similar studies in other public health care systems.

Impact of Thin Meconium on Delivery and Early Neonatal Outcomes.

Several reports regarding the effects of thin meconium on maternal and neonatal outcomes are contradictory. This study evaluated the risk factors and obstetrical outcomes during deliveries complicated with thin meconium. This retrospective cohort study included all women with a singleton pregnancy, who underwent trial of labor >24 weeks of gestation, in a single tertiary center, over a six-year period. Obstetrical, delivery, and neonatal outcomes were compared between deliveries with thin meconium (thin meconium group) to deliveries with clear amniotic fluid (control group). Included in the study were 31,536 deliveries. Among them 1946 (6.2%) were in the thin meconium group and 29,590 (93.8%) were controls. Meconium aspiration syndrome was diagnosed in eight neonates in the thin meconium group and in none of the controls (0.41%, p < 0.001). In multivariate logistic regression analysis, the following adverse outcomes were found to be independently associated with increased odds ratio (OR) for thin meconium: intrapartum fever (OR 1.37, 95% CI 1.1-1.7), instrumental delivery (OR 1.26, 95% CI 1.09-1.46), cesarean delivery for non-reassuring fetal heart rate (OR 2.0, 95% CI 1.68-2.46), and respiratory distress requiring mechanical ventilation (OR 2.06, 95% CI 1.19-3.56). Thin meconium was associated with adverse obstetrical, delivery, and neonatal outcomes that should receive extra neonatal care and alert the pediatrician.

Paracetamol Treatment for Patent Ductus Arteriosus, an Apparent Association with Acute Hemolysis in Three Preterm Infants: Case Series.

We report three preterm infants who were treated with paracetamol for hemodynamically significant patent ductus arteriosus and developed acute hemolysis. No other apparent cause of acute hemolysis was found during Neonatal Intensive Care Unit hospitalization. All three infants were born within 1 year. As this side effect of paracetamol has not been reported previously and many preterm infants receive paracetamol for PDA closure, we advocate awareness. We cannot be sure whether the hemolysis occurred due to an underlying cause that was augmented by paracetamol or whether the drug itself caused acute hemolysis in these preterm infants.

Acute appendicitis in children: Reexamining indications for conservative treatment - A large prospective analysis.

INTRODUCTION: Conservative antibiotic treatment (CAT) for uncomplicated acute appendicitis (AUA) in children has been proven safe and efficacious. However, as data accumulate, high rates of recurrent appendicitis and subsequent appendectomy have been reported. This prospective longitudinal study evaluated risk-factors for recurrent AUA after CAT in a large cohort, with long-term follow-up. MATERIALS AND METHODS: Children ages 5 to 16 years admitted to the Department of Pediatric Surgery from 2014 through 2018, diagnosed with AUA were eligible for CAT. We recorded their age, appendix outer diameter, white blood cell counts, C-reactive protein and other related signs and symptoms associated with AUA. Clinical and ultrasonographic follow-up was carried out until follow-up data collection ceased according to the study design (2014-2019). RESULTS: The cohort included 646 children who were initially treated successfully with CAT. Among them, 180 (28%) were readmitted for recurrent acute appendicitis during the follow-up period and 138 (21%) eventually had appendectomy. Overall success of 79% for CAT was recorded in this cohort. A multivariable model including; age, sex, appendiceal diameter, WBC and CRP, found the factors of older age, larger outer appendiceal diameter and high WBC counts significantly related to appendectomy during the follow-up period. We offer a decision tree model to predict appendectomy probabilities for patients based on their prognostic measurements. CONCLUSION: CAT in AUA in children should consider older age, larger outer appendiceal diameter and high WBC counts as risk-factors for recurrent AUA and subsequent appendectomy. The proposed decision tree model may help both clinicians and parents before CAT is chosen. LEVEL OF EVIDENCE: Level 2.

Music Therapy Intervention in an Open Bay Neonatal Intensive Care Unit Room Is Associated with Less Noise and Higher Signal to Noise Ratios: A Case-Control Study.

BACKGROUND: Noise reduction in the Neonatal Intensive Care Unit (NICU) is important for neurodevelopment, but the impact of music therapy on noise is not yet known. OBJECTIVE: To investigate the effect of music therapy (MT) on noise levels, and whether individual MT (IMT) or environmental MT (EMT) increases meaningful signal-to-noise ratios (SNR). STUDY DESIGN: This case-control study was conducted in a level III NICU. Noise levels were recorded simultaneously from two open bay rooms, with a maximum of 10 infants in each room: one with MT and the other without. MT sessions were carried out for approximately 45 min with either IMT or EMT, implemented according to the Rhythm Breath and Lullaby principles. Noise production data were recorded for 4 h on 26 occasions of EMT and IMT, and analyzed using R version 4.0.2 software. RESULTS: Overall average equivalent continuous noise levels (Leq) were lower in the room with MT as compared to the room without MT (53.1 (3.6) vs. 61.4 (4.7) dBA, p = 0.02, d = 2.1 (CI, 0.82, 3.42). IMT was associated with lower overall Leq levels as compared to EMT (51.2 vs. 56.5 dBA, p = 0.04, d = 1.6 (CI, 0.53, 1.97). The lowest sound levels with MT occurred approximately 60 min after the MT started (46 ± 3.9 dBA), with a gradual increase during the remaining recording time, but still significantly lower compared to the room without MT. The SNR was higher (18.1 vs. 10.3 dBA, p = 0.01, d = 2.8 (CI, 1.3, 3.86)) in the room with MT than in the room without MT. CONCLUSION: Integrating MT modalities such as IMT and EMT in an open bay NICU room helps reduce noise. Both MT modalities resulted in higher SNR compared to the control room, which may indicate that they are meaningful for the neurodevelopment of preterm infants.

Regional Splanchnic Oxygenation during Continuous versus Bolus Feeding among Stable Preterm Infants.

INTRODUCTION: There is no agreement regarding the best method for tube-feeding preterm infants. Few studies, to date, have evaluated the influence of different methods of enteral feeding on intestinal oxygenation. The use of near-infrared spectroscopy (NIRS) has permitted the noninvasive measurement of splanchnic regional oxygenation (rSO2S) in different clinical conditions. The aim of this prospective, single-center study was to compare rSO2S during continuous versus bolus feeding among stable preterm infants. METHODS: Twenty-one preterm infants, less than 32 weeks gestation and appropriate for gestational age, were enrolled. All infants were clinically stable and on full tube feedings. Each infant received a bolus feeding initially (20 min duration), and after 3 h, a continuous feeding (5 h duration). Infants were evaluated 30 min before and 30 min after the bolus and continuous feedings. The regional splanchnic saturation (rSO2S) was measured using near-infrared spectroscopy (NIRS) technology and systemic saturation was measured with pulse oximetry. From these measurements, we calculated the splanchnic fractional oxygen extraction ratio (FOES) for each of the four intervals. RESULTS: rSO2S decreased after continuous vs. bolus feeding (p = 0.025), while there was a trend toward decreased SaO2 after bolus feeding (p = 0.055). The FOES, which reflects intestinal oxygen extraction, was not affected by the feeding mode (p = 0.129). DISCUSSION/CONCLUSION: Continuous vs. bolus feeding decreases rSO2S but does not affect oxygen extraction by intestinal tissue; after bolus feeding there was a trend towards decreased systemic saturation.

Effects of Live Music Therapy on Autonomic Stability in Preterm Infants: A Cluster-Randomized Controlled Trial.

Unbuffered stress levels may negatively influence preterm-infants' autonomic nervous system (ANS) maturation, thus affecting neurobehavior and psycho-emotional development. Music therapy (MT) is an evidence-based treatment modality in neonatal care. When coupled with skin-to-skin care (SSC), it may reduce stress responses in both preterm infants and their parents and enhance family-centered care. Accordingly, we aimed to compare the effects of combined MT and SSC and SSC alone on ANS stabilization in preterm infants. In a single-center, cluster-randomized trial design, ten two-month time-clusters were randomized to either combined MT and SSC or SSC alone. Families of preterm infants were offered two sessions of the allocated condition in the NICU, and a three-month follow up session at home. The primary outcome variable was stabilization of the ANS, defined by change in the high frequency (HF) power of heart rate variability (HRV) during the second session. Secondary outcomes included other HRV measures, parent-infant attachment, and parental anxiety at each session. Sixty-eight families were included. MT combined with SSC improved infants' ANS stability, as indicated by a greater increase in HF power during MT compared to SSC alone (mean difference 5.19 m2/Hz, SE = 1.27, p < 0.001) (95% confidence interval 0.87 to 2.05). Most secondary outcomes were not significantly different between the study groups. MT contributes to preterm-infants' autonomic stability, thus laying an important foundation for neuro-behavioral and psycho-emotional development. Studies evaluating longer-term effects of MT on preterm infants' development are warranted.

Outcome of singleton preterm small for gestational age infants born to mothers with pregnancy-induced hypertension. A population-based study.

BACKGROUND: Pregnancy-induced hypertension (PIH) has been associated with a decreased risk of infant mortality in small for gestational age (SGA) preterm infants. OBJECTIVE: To evaluate the influence of PIH on mortality and major neonatal morbidities in singleton preterm SGA infants, in the presence and absence of acute pregnancy complications. METHODS: Population-based observational study of singleton SGA infants, born at 24 to 32 weeks gestation in the period 1995-2010 (n = 2139). Multivariable logistic regression analyses were used to assess the independent effect of PIH on mortality and neonatal morbidities. Acute pregnancy complications comprised premature labor, premature rupture of membranes >6 h, antepartum hemorrhage and clinical chorioamnionitis. RESULTS: In the absence of pregnancy complications, the odds ratio (95% confidence interval) for mortality (0.77; 0.50-1.16), survival without severe neurological morbidity (1.14; 0.79-1.65) and survival without bronchopulmonary dysplasia (BPD) (0.85; 0.59-1.21) were similar in the PIH versus no-PIH groups. In the presence of pregnancy complications, mortality (0.76; 0.40-1.44), survival without severe neurological morbidity (1.16; 0.64-2.12) and survival without BPD (1.04; 0.58-1.86) were also similar in the PIH versus no-PIH groups. CONCLUSIONS: PIH was not associated with improved outcome in preterm SGA infants, both in the presence and absence of acute pregnancy complications.