Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula: A Randomized Clinical Trial.

Importance: Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. Objective: To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months' corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days' gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. Intervention: Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. Main Outcomes and Measures: The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months' corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months' corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. Results: Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent's race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months' corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, -0.77 [95% CI, -3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, -1% [95% CI, -4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, -5% [95% CI, -9% to -2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d]). Conclusions and Relevance: Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months' corrected age did not differ between infants fed donor milk or preterm formula. Trial Registration: ClinicalTrials.gov Identifier: NCT01534481.

Neonatal resuscitation program (NRP) guidelines and timing of major resuscitation events in delivery rooms at a level III NICU: Understanding deviations.

Objective: To describe the timing of major resuscitation events in the Delivery room. Methods: A retrospective study of neonates born at a level III birthing hospital who received chest compressions in the delivery room was conducted. The timing of the resuscitation events i.e., intubation, UVC, endotracheal (ETT), epinephrine and intravenous (IV) epinephrine were described. The timing of these events were compared for deliveries with the presence of neonatology team. Results: 51 neonates were included. The primary outcome occurred in 28 (65%) of deliveries. An alternate airway was secured at 4.24 ± 5.9 minutes. Endotracheal epinephrine and IV epinephrine were administered at a mean time of 3.98 ± 3 minutes and 10.87± 5.18 minutes after the initiation of chest compressions respectively. Conclusion: Data from real-life cases on the timeline of events suggest that major resuscitation events as suggested by Neonatal Resuscitation Program Guidelines, are often significantly delayed.

PepAnalyzer: predicting peptide properties using its sequence.

Peptides are short linear molecules consisting of amino acids that play an essential role in most biological processes. They can treat diseases by working as a vaccine or antimicrobial agent and serves as a cancer molecule to deliver the drug to the target site for the treatment of cancer. They have the potential to solve the drawbacks of current medications and can be industrially produced in large quantities at low cost. However, poor chemical and physical stability, short circulating plasma half-life, and solubility are some issues that need solutions before they can be used as therapeutics. PepAnalyzer tool is a user-friendly tool that predicts 15 different properties such as binding potential, half-life, transmembrane patterns, test tube stability, charge, isoelectric point, molecular weights, and molar extinction coefficients only using the sequence. The tool is designed using BioPython utility and has even results with standard tools, such as Expasy, EBI, Genecorner, and Geneinfinity. The tool assists students, researchers, and the pharmaceutical sector. The PepAnalyzer tool's online platform is accessible at the link: http://www.iksmbrlabdu.in/peptool .

Comparative Effectiveness of Surgical Ligation and Catheter Closure of Patent Ductus Arteriosus in Preterm Infants.

To evaluate the association, if any, between closure modality (surgical ligation SL vs. catheter CC) of a hemodynamically significant patent ductus arteriosus (PDA), after failure of or contraindication to medical therapy, and immediate procedural complications, and post-procedure physiologic status in preterm (gestational age < 32 weeks) infants. In this single-center retrospective cohort study, data were accessed on infants < 32 weeks gestation, who underwent SL or CC of PDA, born from 2019-2021. The choice of modality was determined by parents, after they were provided information on both procedures. Our cohort (n = 112) included 36 (32.1%) infants who underwent SL while 76 (67.9%) underwent CC. The SL group of infants were significantly more immature at birth, younger on admission to the level IV NICU and received more mean (SD) surfactant doses than the CC group. Higher proportions of infants in the SL group had 5-min Apgar scores ≤ 5, seizures, severe intracranial hemorrhage and had received medical therapy for PDA. Both procedures were highly efficacious, with 1 unsuccessful device placement attempt and had low associated adverse events. Two (2.6%) infants had device migration 24 h after CC. SL was associated with a higher rate of immediate postoperative hypothermia whereas, in the CC group, mean airway pressure was significantly lower 48 h after, compared to before the procedure. SL and CC are comparable in short-term efficacy and safety for PDA closure. Long-term outcomes data are needed following both procedures.

Comparative Growth Outcomes in Preterm Infants Fed Either Mother's Own Milk or Donor Human Milk.

Objective: To compare growth velocity (GV) in preterm infants fed mother's own milk (MOM) fortified with human milk-based fortifier (HMBF) to those who received donor human milk (DHM) fortified with HMBF. Study Design: A retrospective study of preterm infants with birth weight <1,250 g receiving an exclusive human milk diet. Maternal and infant charts were reviewed for feeding, growth, and short-term neonatal morbidities. Results: On regression analysis, after adjusting (gestational age, multiple births, antenatal steroids, and small for gestational age), no significant difference was observed between the two groups in GV from birth to 32 weeks postmenstrual age (ß-coefficient 0.83, 95% confidence interval [CI]: -0.47 to 2.14, p = 0.21), GV from the day of regaining of birth weight to discharge (ß-coefficient -0.015, 95% CI: -1.08 to 1.05, p = 0.98). The rate of Grade 3 and 4 intraventricular hemorrhage was significantly higher in the DHM group (19.6% compared to 5.5% in MOM, p = 0.03). Conclusion: At our institution, there was no difference in GV of preterm infants fed HMBF-fortified MOM versus HMBF-fortified DBM.

Population-Level Study on Fetal Deaths and Preterm Births during SARS-CoV-2 Pandemic in the State of Michigan.

OBJECTIVE: The aim of the study is to explore the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on preterm birth at different gestational ages and fetal death in the state of Michigan. STUDY DESIGN: Data on live births and fetal deaths in the state of Michigan from March to November in the years 2017 through 2020 were obtained from Michigan Department of Health and Human Services (MDHHS). Preterm birth rate, fetal death rate (per 1,000 live births) overall and stratified by race and maternal comorbidities during the period of pandemic (March-November 2020) were compared with the same period (March-November) in the prepandemic years (2017-2019). RESULTS: Of 328,879 live births and 1,470 fetal deaths during the study period, 77,983 live births and 242 fetal deaths were reported in 2020. Compared with prepandemic years, fetal death rate per 1,000 live births was significantly lower in 2020 (3.1 vs. 4.7 [2017], 5.2 [2018], 4.4 [2019], p-value <0.001). The adjusted risk for fetal death in 2020 was decreased (odds ratio [OR] = 0.64 [95% confidence interval (CI): 0.56-0.74], p <0.0001), compared with prepandemic years. Fetal death was significantly associated with African-American race, pregnancy hypertension and prepregnancy diabetes. No significant difference in the proportion of preterm births (<37 weeks' gestation) was noted between pandemic and prepandemic years (9.9 vs. 10.0%, p = 0.50). There was no significant difference in the risk of preterm birth across gestational age strata (<28, 28-316/7, 32-366/7, 37-416/7, and >42 weeks) between pandemic and prepandemic years on multinomial analysis. Significant associations with preterm birth across all years included African American race, lower level of maternal education, pregnancy-induced hypertension, chronic hypertension, prepregnancy diabetes, congenital anomalies, previous preterm birth, and prolonged rupture of membranes >12 hours. CONCLUSION: Fetal death rate was significantly lower whereas preterm births remained unchanged during pandemic in comparison with prepandemic years in the state of Michigan. KEY POINTS: · A decrease in fetal death rate was noted during SARS CoV-2 pandemic in the State of Michigan.. · Overall state-wide rates of preterm birth did not change in 2020, compared to previous years.. · Significant risk factors associated with preterm birth and fetal deaths did not differ between prepandemic and pandemic years..

Effect of an exclusive human milk diet on feeding tolerance in preterm infants.

OBJECTIVE: To compare the time to full enteral feeds in preterm infants fed exclusive human milk (EHM) - mother's own milk (MOM) fortified with human milk-based fortifier (HMBF), to those who received partial human milk (PHM) - MOM fortified with bovine milk-based fortifier (BMBF), and exclusive formula. STUDY DESIGN: A single-center retrospective study of infants with birth weight <1250 g from 2013 to 2018. Data on feeding, growth and other short-term neonatal morbidities were collected. RESULTS: On regression analysis, time to full enteral feeds was significantly higher in PHM compared to EHM group (ß-coefficient 4.14, 95% CI 0.00-8.29) and formula-fed group compared to EHM (ß-coefficient 4.3, 95% CI 0.32-8.20). No significant differences in growth velocity, length of stay and other morbidities were found between the groups. CONCLUSION: Infants in EHM had better feeding tolerance and reached their enteral feed goals sooner compared to PHM and formula-fed groups.

Breast milk vs 24% sucrose for procedural pain relief in preterm neonates: a non-inferiority randomized controlled trial.

OBJECTIVES: To compare the pain scores between the two groups, breast milk (BM) and 24% sucrose, in preterm neonates undergoing automated heel lance for the blood draw. METHODS: The study is designed as a randomized, single-blinded, non-inferiority trial. Infants born between 30 1/7weeks and 36 6/7 weeks of gestation were randomly assigned to receive either 24% sucrose or expressed BM. The Premature Infant Pain Profile-Revised (PIPP-R) was utilized to provide pain scores. RESULTS: No differences were noted in the baseline characteristics between the two groups. The quantile regression estimates for PIPP-R scores during the procedure were statistically non-significant at all percentile levels of distribution (50%ile coefficient 0, 95% CI -0.49 to 0.49). CONCLUSION: We conclude that BM is not inferior to 24% sucrose in providing analgesia during heel lance in moderate and late preterm infants. TRIAL REGISTRATION: This trial was registered at www. CLINICALTRIALS: gov (identifier NCT04898881).

Haemodynamic impact of chest compressions in the delivery room.

Among 65 neonates with encephalopathy undergoing cooling, 30 (46.1%) received chest compressions during delivery room resuscitation. Despite differences in encephalopathy severity, early (<24 hours) biventricular function on echocardiogram (fractional area change, myocardial performance indices, systolic to diastolic duration ratios, tricuspid annular plane systolic excursion) was comparable between groups with and without chest compressions. Epinephrine receipt was associated with abnormal tricuspid annular plane systolic excursion.

Postdischarge Adverse Events Among Neonates Admitted to the Neonatal Intensive Care Unit.

OBJECTIVES: We aimed to determine the rate of postdischarge adverse events (AEs), classify the types of postdischarge AEs, and identify risk factors for postdischarge AEs among neonates admitted to the neonatal intensive care unit (NICU). STUDY DESIGN: This was a prospective cohort study of neonates admitted to the NICU from February 2017 through June 2019. We enrolled 170 neonates from a level 4 NICU who were being discharged home and whose parents can speak English and could be contacted after discharge. The main outcome of the study was postdischarge AEs based on structured telephone interviews, health record review, and adjudication by 2 blinded, trained physicians using a previously established methodology. RESULTS: Fourteen percent of 170 neonates admitted to the NICU experienced postdischarge AEs, with 48% being either preventable or ameliorable. Adverse drug events and procedural complications comprised most of the AEs (48%), but most of the preventable and ameliorable AEs were due to management, therapeutic, or diagnostic errors. Seventy-nine percent of neonates who suffered an AE experienced either a readmission to the hospital or an emergency department visit. Neonates admitted to a level 4 NICU from another NICU (level 1, 2, or 3) (adjusted odds ratio, 3.62; 95% confidence interval, 1.27-12.60; P = 0.01) and those 28 to 36 weeks (adjusted odds ratio, 11.38; 95% confidence interval, 1.67-127.98; P = 0.01) had a significantly higher risk of AEs at discharge. CONCLUSIONS: Neonates discharged from a level 4 NICU were at high risk for experiencing postdischarge AEs. The identification of AE types and risk factors can be used to guide efforts to develop interventions to improve neonatal patient safety during the postdischarge period.

Clinical Characteristics of Mother-Infant Dyad and Placental Pathology in COVID-19 Cases in Predominantly African American Population.

Objective In this currently evolving coronavirus disease 2019 (COVID-19) pandemic, the evidence is scarce about the impact of COVID-19 infection on women in labor and neonates in an inner city African-Americans (AA) population. The objective of this study was to evaluate the clinical outcomes and placental pathology in mother-infant dyads in COVID-19 cases. Study Design Retrospective chart review was conducted on 34 COVID-19 positive mother-infant dyads to study their baseline characteristics and outcomes. Placental pathology was reviewed by two perinatal pathologists. Results COVID-19 was noted in 3% of pregnant women who delivered in our institution. The majority (82%) of them were asymptomatic. Out of the four mothers who were symptomatic, only three (9%) required supplemental oxygen. None of them required invasive ventilation. All the neonates tested negative for COVID-19 at 24 hours of age. There were no gross or microscopic pathological abnormalities detected that could be definitely associated with any COVID-19 related complications during pregnancy in any of the 34 placentas. Conclusion COVID-19 does not appear to increase morbidity and mortality among pregnant women and their neonates in a predominantly AA population. Our study did not find any evidence of vertical transmission of COVID-19 infection nor any specific findings on placental pathology. Key Points Majority of women infected by coronavirus disease 2019 (COVID-19) during labor were asymptomatic.None of the newborns tested positive for COVID-19 at 24 hours of age.Placental pathology findings were nonspecific in COVID-19 mothers.

Analyzing the Effect of Vaccination Over COVID Cases and Deaths in Asian Countries Using Machine Learning Models.

Coronavirus Disease 2019 (COVID-19) is spreading across the world, and vaccinations are running parallel. Coronavirus has mutated into a triple-mutated virus, rendering it deadlier than before. It spreads quickly from person to person by contact and nasal or pharyngeal droplets. The COVID-19 database 'Our World in Data' was analyzed from February 24, 2020, to September 26, 2021, and predictions on the COVID positives and their mortality rate were made. Factors such as Vaccine data for the First and Second Dose vaccinated individuals and COVID positives that influence the fluctuations in the COVID-19 death ratio were investigated and linear regression analysis was performed. Based on vaccination doses (partial or complete vaccinated), models are created to estimate the number of patients who die from COVID infection. The estimation of variance in the datasets was investigated using Karl Pearson's coefficient. For COVID-19 cases and vaccination doses, a quartic polynomial regression model was also created. This predictor model helps to predict the number of deaths due to COVID-19 and determine the susceptibility to COVID-19 infection based on the number of vaccine doses received. SVM was used to analyze the efficacy of models generated.

Outcomes Following Post-Hemorrhagic Ventricular Dilatation among Infants of Extremely Low Gestational Age.

OBJECTIVE: To assess outcomes following post-hemorrhagic ventricular dilatation (PHVD) among infants born at ≤26 weeks of gestation. STUDY DESIGN: Observational study of infants born April 1, 2011, to December 31, 2015, in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and categorized into 3 groups: PHVD, intracranial hemorrhage without ventricular dilatation, or normal head ultrasound. PHVD was treated per center practice. Neurodevelopmental impairment at 18-26 months was defined by cerebral palsy, Bayley Scales of Infant and Toddler Development, 3rd edition, cognitive or motor score <70, blindness, or deafness. Multivariable logistic regression examined the association of death or impairment, adjusting for neonatal course, center, maternal education, and parenchymal hemorrhage. RESULTS: Of 4216 infants, 815 had PHVD, 769 had hemorrhage without ventricular dilatation, and 2632 had normal head ultrasounds. Progressive dilatation occurred among 119 of 815 infants; the initial intervention in 66 infants was reservoir placement and 53 had ventriculoperitoneal shunt placement. Death or impairment occurred among 68%, 39%, and 28% of infants with PHVD, hemorrhage without dilatation, and normal head ultrasound, respectively; aOR (95% CI) were 4.6 (3.8-5.7) PHVD vs normal head ultrasound scan and 2.98 (2.3-3.8) for PHVD vs hemorrhage without dilatation. Death or impairment was more frequent with intervention for progressive dilatation vs no intervention (80% vs 65%; aOR 2.2 [1.38-3.8]). Death or impairment increased with parenchymal hemorrhage, intervention for PHVD, male sex, and surgery for retinopathy; odds decreased with each additional gestational week. CONCLUSIONS: PHVD was associated with high rates of death or impairment among infants with gestational ages ≤26 weeks; risk was further increased among those with progressive ventricular dilation requiring intervention.

Feeding during transfusion and the risk of necrotizing enterocolitis in preterm infants.

OBJECTIVE: To evaluate the effect of withholding feeds during transfusion on transfusion associated acute gut injury (TRAGI). STUDY DESIGN: Data were collected on 125 preterm infants before and after the practice of withholding feeds for 12-24 h during transfusion was instituted. Logistic regression was used to examine effects of withholding feeds on TRAGI rates. RESULTS: A total of 19 (15%) infants developed NEC; 6/19 (32%) had TRAGI. Postnatal hydrocortisone use was associated with TRAGI (OR 8.97; 95% CI 1.17-68.46, p = 0.034). There was no difference in NEC rates (15.8 vs. 14.7%) and the proportions (22.2 vs. 40%) of TRAGI in the two time periods before and after instituting the standardized feeding regimen and practice of holding feeds during transfusion. CONCLUSION: No significant decrease was noted in the rates of TRAGI after feeds were withheld during transfusion. Further studies are warranted to explore the relationship between feeds during transfusion and NEC.

Delivery Room Resuscitation and Short-Term Outcomes in Moderately Preterm Infants.

OBJECTIVES: To describe the frequency and extent of delivery room resuscitation and evaluate the association of delivery room resuscitation with neonatal outcomes in moderately preterm (MPT) infants. STUDY DESIGN: This was an observational cohort study of MPT infants delivered at 290/7 to 336/7 weeks' gestational age (GA) enrolled in the Neonatal Research Network MPT registry. Infants were categorized into 5 groups based on the highest level of delivery room intervention: routine care, oxygen and/or continuous positive airway pressure, bag and mask ventilation, endotracheal intubation, and cardiopulmonary resuscitation including chest compressions and/or epinephrine use. The association of antepartum and intrapartum risk factors and discharge outcomes with the intensity of resuscitation was evaluated. RESULTS: Of 7014 included infants, 1684 (24.0%) received routine care and no additional resuscitation, 2279 (32.5%) received oxygen or continuous positive airway pressure, 1831 (26.1%) received bag and mask ventilation, 1034 (14.7%) underwent endotracheal intubation, and 186 (2.7%) received cardiopulmonary resuscitation. Among the antepartum and intrapartum factors, increasing GA, any exposure to antenatal steroids and prolonged rupture of membranes decreased the likelihood of receipt of all levels of resuscitation. Infants who were small for GA (SGA) had increased risk of delivery room resuscitation. Among the neonatal outcomes, respiratory support at 28 days, days to full oral feeds and length of stay were significantly associated with the intensity of delivery room resuscitation. Higher intensity of resuscitation was associated with increased risk of mortality. CONCLUSIONS: The majority of MPT infants receive some level of delivery room resuscitation. Increased intensity of delivery room interventions was associated with prolonged respiratory and nutritional support, increased mortality, and a longer length of stay.

Chorioamnionitis in the Development of Cerebral Palsy: A Meta-analysis and Systematic Review.

CONTEXT: Chorioamnionitis (CA) has often been linked etiologically to cerebral palsy (CP). OBJECTIVES: To differentiate association from risk of CA in the development of CP. DATA SOURCES: PubMed, Cochrane Library, Embase, and bibliographies of original studies were searched by using the keywords (chorioamnionitis) AND ((cerebral palsy) OR brain). STUDY SELECTION: Included studies had to have: (1) controls, (2) criteria for diagnoses, and (3) neurologic follow-up. Studies were categorized based on: (1) finding incidence of CP in a CA population, or risk of CP; and (2) incidence of CA in CP or association with CP. DATA EXTRACTION: Two reviewers independently verified study inclusion and extracted data. RESULTS: Seventeen studies (125 256 CA patients and 5 994 722 controls) reported CP in CA. There was significantly increased CP inpreterm histologic chorioamnionitis (HCA; risk ratio [RR] = 1.34, P < .01), but not in clinical CA (CCA). Twenty-two studies (2513 CP patients and 8135 controls) reported CA in CP. There was increased CCA (RR = 1.43, P < .01), but no increase in HCA in preterm CP. Increased HCA was found (RR = 4.26, P < .05), as well as CCA in term/near-term CP (RR = 3.06, P < .01). CONCLUSIONS: The evidence for a causal or associative role of CA in CP is weak. Preterm HCA may be a risk factor for CP, whereas CCA is not. An association with term and preterm CP was found for CCA, but only with term CP for HCA.

Fifteen years of genetic testing from a London developmental clinic.

OBJECTIVE: To evaluate genetic disease among children referred to a community paediatric clinic. DESIGN: Retrospective cohort study. SETTING: Community paediatric clinic, Tower Hamlets, London. PATIENTS: All patients seen for first time in the Child Development Team (CDT) clinic between 1999 and 2013. INTERVENTIONS: Clinical notes were reviewed. Genetic test results were obtained. Exploratory Excel analysis was performed. Patients without an identified genetic disorder were labelled 'more likely genetic cause' if they had at least two out of three risk factors: developmental delay, congenital abnormality or parental consanguinity, and 'unlikely genetic cause' if they had one or no risk factors, or an obvious alternative cause. MAIN OUTCOME MEASURES: Prevalence of genetic diagnoses and parental consanguinity, undertaking of genetic tests, predicted likelihood of a genetic cause among unsolved patients. RESULTS: 749 patients were included. 404 (53.9%) had undergone genetic testing and 158 of those tested (39.1%) had a confirmed genetic diagnosis. Parental relatedness was documented in 461 patients, of which 128 (27.8%) had first-cousin parents. The number of patients undergoing genetic testing increased over time. Aneuploidies and syndromic/Mendelian disorders were most common. Of the 591 patients without a genetic diagnosis, 29.9% were classified 'more likely genetic cause'. Patients with consanguineous parents were significantly more likely to have a diagnosed genetic disorder than those with non-consanguineous parents (43/128 vs 72/333), particularly an autosomal recessive condition (27/43 vs 6/72). CONCLUSIONS: Genetic disease was common and genetic testing is important in evaluating children in this clinic. Consanguinity increases the likelihood of autosomal recessive disease.