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Objectives: To assess whether continuous non-invasive pCO2 monitoring by transcutaneous pCO2 monitor (TCpCO2) among extremely low birth weight (ELBW) premature infants, during the first week of life, will decrease the rate of high-grade intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL) or the combined outcome of IVH/PVL and death. Methods: This was a prospective, observational, multicenter study. Due to ethical constraints, allocation was based on TCpCO2 monitor availability. ELBW infants were either monitored by TCpCO2 monitor (Sentec, Therwil, Switzerland) (study group), or recruited to the control group if a TCpCO2 monitor was not available. Results: A total of 132 ELBW infants participated in the study. The size of the study group (106 infants) and the control group (26 infants) differed because monitor availability increased during the study period reflecting change in standard of care. The groups had comparable gestational age and baseline characteristics. No difference was found in the rate of IVH/PVL in the study vs. control groups (10% vs. 4%; p = 0.7, respectively), or in the combined outcome of PVL/IVH and death (16% vs. 15%; p = 1.0, respectively). Conclusions: This study demonstrates the challenges in conducting a prospective controlled trial in a rapidly evolving medical field. While the study began with a clear equipoise, this balance shifted as the care team gained more experience with TCpCO2 monitoring among the study population, despite the absence of new clinical evidence to justify such a shift. Consequently, the small control group limited our ability to draw definitive conclusions regarding the study's objective. However, our findings may increase awareness of continuous non-invasive pCO2 monitoring in extremely premature infants. [ABSTRACT FROM AUTHOR]

Introduction: Hypospadias is a syndrome of penile maldevelopment. The primary goal of hypospadias surgery is to create a penis with normal appearance and function. Historically, the outcome of hypospadias repair has been assessed based on the need for reoperation due to urethroplasty complications (UC), including fistula formation, dehiscence, meatal stenosis, or development of a urethral stricture. The Glans–Urethral Meatus–Shaft (GMS) score is a standardized tool to predict UC. Analysis of the cosmetic outcomes of hypospadias repair based on the appearance of the reconstructed penis has been validated, and standardized scores have been published. The Hypospadias Objective Penile Evaluation (HOPE) score is a validated questionnaire used to assess postoperative cosmetic outcomes. Although predictors of surgical outcomes and UC have been well documented, predictors of optimal cosmetic outcomes are lacking in the literature. Furthermore, reoperation due to cosmetic considerations has been poorly reported. Objective: To identify predictors of cosmetic outcomes after hypospadias repair and to assess the reoperation rate according to cosmetic considerations. Materials and Methods: This prospective cohort study included 126 boys who underwent primary hypospadias repair. The severity of hypospadias, degree of penile curvature, glans width, preoperative HOPE, and GMS scores were documented. The standard technique for single-stage repairs, the tubularized incised plate urethroplasty, was performed. The primary endpoint was cosmetic outcomes evaluated by the HOPE score questionnaire six months postoperatively. Optimal cosmetic results were defined by HOPE scores ≥ 57. Results: The study population consisted of the following cases: 87 (69%) subcoronal, 32 (25%) shaft, and 7 (6%) proximal hypospadias. Among the study participants, 102 boys (81%) had optimal cosmetic results (HOPE ≥ 57), and 24 boys (19%) had surgeries with suboptimal cosmetic outcomes (HOPE < 57). Ancillary procedures were performed in 21 boys (16%), of which 14 (11%) were solely for cosmetic considerations, and 7 were secondary to UC. Using the Receiver Operating Characteristic analysis of potential predictors of optimal cosmetic outcomes, the preoperative HOPE score had the highest area under the curve (AUC = 0.79; 95% CI 0.69–0.89, p < 0.001). After multivariable analysis, the degree of penile chordee (p = 0.013), glans width (p = 0.003), GMS score (p = 0.007), and preoperative HOPE score (p = 0.002) were significant predictors of cosmetic outcomes. Although meatal location predicted suboptimal cosmetic results in univariate analysis, it was not a factor in multivariable analysis. Conclusions: Over 80% of boys undergoing hypospadias repair achieved optimal cosmetic outcomes. More than 10% of cases underwent ancillary procedures, secondary solely to cosmetic considerations. Predictors of optimal cosmetic outcomes after hypospadias surgery included degree of chordee, glans width, and preoperative HOPE and GMS scores, which were the best predictors of satisfactory cosmetic results. Although meatal location is the main predictor of UC, it was not a predictor for cosmetic outcomes. Factors affecting cosmetic outcomes should be clearly explained to parents during the preoperative consultation. [ABSTRACT FROM AUTHOR]

Music therapy (MT) is a part of standard care in neonatal intensive care units (NICU) in many countries, and in some countries is provided as a post-discharge service as well. However, it is rare that preterm families are offered continuous MT services from birth through their first months at home. Affiliated with a recent longitudinal, controlled trial of MT for parent-infant bonding and an associated qualitative study exploring lived experiences of MT post-discharge in an Israeli cohort of parent participants, this study aimed to understand parents' experiences of engaging in longer-term MT with their preterm infants, spanning from birth into six months in a different Israeli cohort from the main trial. We completed an Interpretative Phenomenological Analysis (IPA) of parents' experiences of music therapy with their preterm infants. Semi-structured interviews intertwining listening to audio recordings from MT sessions were conducted with seven participants from five families of the main trial. The interviews were transcribed and analyzed following principles of IPA. The analysis resulted in the construction of two super-ordinate themes: (a) MT as a therapeutic haven, and (b) MT enabling integration of music into relationship over time. Experiences of a small cohort of Israeli parents suggest that MT spanning from birth to home may play a role in supporting parental musical agency and enhancing parent-infant relationship building. [ABSTRACT FROM AUTHOR]

Extremely low birth weight (ELBW) premature infants are particularly susceptible to hypocarbia and hypercarbia, which are associated with brain and lung morbidities. Transcutaneous CO2 (TcCO2) monitoring allows for continuous non-invasive CO2 monitoring during invasive and non-invasive ventilation and is becoming more popular in the NICU. We aimed to evaluate the correlation and agreement between CO2 levels measured by a TcCO2 monitor and blood gas CO2 (bgCO2) among ELBW infants. This was a prospective observational multicenter study. All infants < 1000 g admitted to the participating NICUs during the study period were monitored by a TcCO2 monitor, if available. For each bgCO2 measured, a simultaneous TcCO2 measurement was documented. In total, 1828 pairs of TcCO2–bgCO2 values of 94 infants were collected, with a median (IQR) gestational age of 26.4 (26.0, 28.3) weeks and birth weight of 800 (702, 900) g. A moderate correlation (Pearson: r = 0.64) and good agreement (bias (95% limits of agreement)):(2.9 [−11.8, 17.6] mmHg) were found between the TcCO2 and bgCO2 values in the 25–70 mmHg TcCO2 range. The correlation between the TcCO2 and bgCO2 trends was moderate. CO2 measurements by TcCO2 are in good agreement (bias < 5 mmHg) with bgCO2 among premature infants < 1000 g during the first week of life, regardless of day of life, ventilation mode (invasive/non-invasive), and sampling method (arterial/capillary/venous). However, wide limits of agreement and moderate correlation dictate the use of TcCO2 as a complementary tool to blood gas sampling, to assess CO2 levels and trends in individual patients. [ABSTRACT FROM AUTHOR]

Information on the effect of bloody amniotic fluid during labor at term is scarce. This study assessed risk factors and adverse outcomes in labors with bloody amniotic fluid. During the six years of this study, all nulliparas in our institution, with a trial of labor, were included. Multiple pregnancies and preterm deliveries were excluded. Outcomes were compared between the bloody amniotic fluid group and the clear amniotic fluid group. Overall, 11,252 women were included. Among them, 364 (3.2%) had bloody amniotic fluid and 10,888 (96.7%) had clear amniotic fluid. Women in the bloody amniotic fluid group were characterized by shorter duration of the second stage and higher rate of cesarean section due to non-reassuring fetal heart rate. In addition, there were higher rates of low cord pH (<7.1) and NICU admissions in the bloody amniotic fluid group. In multivariate logistic regression analysis, cesarean delivery, cord blood pH < 7.1, and NICU admission were independently associated with increased odds ratio for bloody amniotic fluid. Bloody amniotic fluid at term is associated with adverse outcomes and must be considered during labor. [ABSTRACT FROM AUTHOR]

The velocity time integral (VTI) is a clinical Doppler ultrasound measurement of blood flow, measured by the area under the wave curve and equivalent to the distance traveled by the blood. This retrospective study assessed the middle cerebral artery (MCA) VTI of fetuses in pregnancies complicated by maternal alloimmunization. Doppler indices of the MCA were retrieved from electronic medical records. Systolic deceleration-diastolic time, systolic acceleration time, VTI, and peak systolic velocity (PSV) were measured at 16–40 weeks gestation. Cases with PSV indicating fetal anemia (cutoff 1.5 MoM) and normal PSV were compared. The study included 255 Doppler ultrasound examinations. Of these, 41 were at 16–24 weeks (group A), 100 were at 25–32 weeks (group B), and 114 were at 33–40 weeks (group C). VTI increased throughout gestation (5.5 cm, 8.6 cm, and 12.1 cm in groups A, B, and C, respectively, p = 0.003). VTI was higher in waveforms calculated to have MCA-PSV ≥ 1.5 MoM compared to those with MCA-PSV < 1.5 MoM (9.1 cm vs. 14.1 cm, respectively, p < 0.001), as was VTI/s (22.04 cm/s vs. 33.75 cm/s, respectively; p < 0.001). The results indicate that the MCA VTI increases significantly among fetuses with suspected anemia, indicating higher perfusion of hemodiluted blood to the brain. This feasible measurement might provide a novel additional marker for the development of fetal anemia. [ABSTRACT FROM AUTHOR]

External cephalic version (ECV) is a cost-effective and safe treatment option for breech presentation at term. Following ECV, fetal well-being is assessed via a non-stress test (NST). An alternative option to identify signs of fetal compromise is via the Doppler indices of the umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV). Inclusion criteria were an uncomplicated pregnancy with breech presentation at term. Doppler velocimetry of the UA, MCA and DV were performed up to 1 h before and up to 2 h after ECV. The study included 56 patients who underwent elective ECV with a success rate of 75%. After ECV, the UA S/D ratio, UA pulsatility index (PI) and UA resistance index (RI) were increased compared to before the ECV (p = 0.021, p = 0.042, and p = 0.022, respectively). There were no differences in the Doppler MCA and DV before or after ECV. All patients were discharged after the procedure. ECV is associated with changes in the UA Doppler indices that might reflect interference in placental perfusion. These changes are probably short-term and have no detrimental effects on the outcomes of uncomplicated pregnancies. ECV is safe; yet it is a stimulus or stress that can affect placental circulation. Therefore, careful case selection for ECV is important. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Orofacial clefts include cleft lip (CL) and cleft palate (CP). This retrospective study assessed the efficacy of prenatal sonographic diagnosis of isolated and non-isolated cases of CL/CP and the postnatal outcomes of these children. Data regarding patients diagnosed and treated in the tertiary orofacial clinic from 2000 to 2020 were retrieved from electronic medical records and telephone-based questionnaires. Isolated CL was found in 7 cases (7.2%), isolated CP in 51 (53%), and combined CL/CP in 38 (39.5%), and 22 cases (23%) were associated with other anomalies. Among 96 cases, 39 (40.6%) were diagnosed prenatally. Isolated CL was diagnosed in 5/7 (71.5%), combined clefts in 29/38 (76.3%), and CP in 7/51 (13.8%). Prenatal chromosomal analysis performed in 32/39 (82%) cases was normal for all. The rate of surgical intervention in the first year of life was 36/38 (94.7%) for combined clefts, 5/7 (71.4%) for CL, and 20/51 (39%) for isolated CP. Most children had speech therapy (23/38 (60.5%), 3/7 (42.8%), and 41/51 (80.3%), respectively) and psychotherapy (6/38 (15.7%), 3/7 (42.8%) and, 15/51 (29.4%), respectively). The accuracy rate of sonographic prenatal diagnosis is low. Our results emphasize the suggested work-up of fetuses with CL and/or CP and improvements to parental counseling, as well as their understanding and compliance regarding post-natal therapeutic plans. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Vitamin D plays a key role in regulating calcium and phosphate metabolism. However, whether maternal vitamin D levels affect fetal bone strength is unclear. This study assessed correlations between maternal 25(OH)D status and neonatal bone strength 25(OH)D levels, these were measured in the maternal and infant cord blood of 81 mother–infant dyads. Bone strength was measured using a quantitative ultrasound (QUS) of tibial bone speed of sound (SOS). Maternal vitamin D intake, medical history and lifestyle were evaluated from questionnaires. Maternal 25(OH)D levels were deficient (<25 nmol/L) in 24.7%, insufficient (25–50 nmol/L) in 37% and sufficient (>50 nmol/L) in 38.3%. The maternal and cord blood 25(OH)D levels correlated (r = 0.85, p < 0.001). Cord blood levels (57.9 ± 33.5 nmol/L) were higher than the maternal blood levels (46.3 ± 23.2: p < 0.001). The mean SOS was 3042 ± 130 m/s. The neonatal SOS and 25(OH)D levels were not correlated. The mean bone SOS levels were comparable in the three maternal and cord blood 25(OH)D groups. No correlation was found between the maternal 25(OH)D levels and the neonatal anthropometrics. Although the 25(OH)D levels were higher in Jewish mothers than they were in Muslim mothers (51.1 ± 22.6 nmol/L vs. 24 ± 14.7 nmol/L, respectively: p = 0.002) and in those who took supplemental vitamin D, the bone SOS levels were comparable. In conclusion, maternal vitamin D levels correlate with cord levels but do not affect bone strength or growth parameters. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Music therapy (MT) interventions and skin-to-skin care (SSC) both aim to address the varied needs of preterm infants, including sensory regulation and stress reduction, inclusion of parents in their infant's care, support of parents' emotional state, and enhancing the parent-infant attachment process. Few studies have investigated the combination of both modalities through randomized controlled trials. Evidence of longer-term effects is missing. This article presents a study protocol that will investigate the effects of combined family-centered MT intervention and SSC on preterm-infants' autonomic nervous system (ANS) stability, parental anxiety levels, and parent-infant attachment quality. 12 clusters with a total of 72 preterm infants, with their parents, will be randomized to one of two conditions: MT combined with SSC or SSC alone. Each parent-infant dyad will participate in 3 sessions (2 in the hospital and a 3-month follow-up). The primary outcome of preterm infants' ANS stability will be measured by the high frequency power of their heart rate variability. Secondary outcomes will be physiological measures and behavioral states in infants and anxiety and attachment levels of parents. This trial will provide important, evidence-based knowledge on the use of the "First Sounds: Rhythm, Breath, and Lullaby" model of MT in neonatal care, through an intervention that is in line with the Newborn Individualized Developmental Care and Assessment Program model for supportive developmental care of preterm infants and their parents. Ethical approval (no. 0283-15) was granted from the local Institutional Review Board in April 2017. This trial is registered in ClinicalTrials.gov, NCT03023267. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article presents an observational study conducted to determine the short-term effects of blood transfusion on iron status, hepcidin, and erythropoietin in stable preterm infants. Topics covered include the materials and methods used in the study, the blood sampling and handling and the statistical analysis procedures used in the study, and details relating to the results obtained from the study. It also discusses the hepcidin changes after red blood cell transfusion (RBCT) in infants.