Quality improvement initiative to reduce Medical Adhesive Related Skin injury (MARSI) in very preterm babies admitted to neonatal intensive care unit.

INTRODUCTION: Sick preterm neonates are most vulnerable to developing skin injuries. Despite sound knowledge and application of evidence-based practices for preventing medical adhesive-related skin injury (MARSI), the incidence of MARSI was 30 events per 1000 adhesive application days in our unit. AIMS AND OBJECTIVES: We aimed to reduce the median MARSI rate from the existing 30 per 1000 MARSI days to <5 per 1000 MARSI over 5 months from June 2023 to October 2023. MATERIAL & METHODS: With the point-of-care quality improvement (QI) approach, a prospective study was planned to reduce the incidence of MARSI among sick very preterm newborns (<32 weeks gestational age) and eventually improve overall skin condition during hospital stay. Sequential Plan-Do-Study-Act cycles were implemented based on the identified risk factors recognised during recurring team discussions. RESULTS: We demonstrated a reduction in the MARSI rate from 30 events per 1000 adhesive applications (during baseline assessment) to zero events per 1000 adhesive applications at the end of the study period. It was temporally related to the assessment of skin risk stratification at admission using a validated tool, regular assessment of neonatal skin condition score based on the skin risk stratification, and reinforcement of MARSI prevention bundle by application of barrier spray. Awareness regarding 'skin injury prevention' bundles was continually generated among healthcare professionals. The MARSI rate remained <5 events per adhesive application in the sustenance phase over 6 months. CONCLUSION: Implementing evidence-based skin care practices resulted in a significant reduction in iatrogenic cutaneous injury events in very preterm neonates.

Comparison of Paladai Cup Against Nifty Cup Feeding in Preterm Low-Birth-Weight Infants: An Open-Labeled Randomized Controlled Trial.

Background: Neonatal Intuitive Feeding Technology (NIFTY) cup feeding has been found to be feasible in preterm low-birth-weight babies. However, literature on direct comparison of the same with paladai feeding is lacking. Methods: In this open-labeled, randomized controlled trial, preterm infants (<34 weeks/<1800 g) on full oral gastric tube feeding for at least 3 consecutive days, eligible to be given a trial of suck and swallow cup feeding, prior to initiation of direct breastfeeding, were randomized to the two feeding intervention groups: paladai cup and Nifty cup. The primary outcome was the time taken from initiation of oral cup feeds to reaching complete gavage-free cup feeds for at least 24 hours. Secondary outcomes were the ease of use of both instruments, the adverse effects during and within 10 minutes after feeding, and anthropometric parameters (head circumference and weight gain). Results: The median (IQR) time taken from initiation to complete transition to full cup feeding for at least 24 hours was not significantly different [4(3,7) days in Nifty cup group versus 3(2,6) days in paladai cup group, p = 0.25]. Mean ± SD weight gain from intervention to discharge was also similar in both the groups (16 ± 6 g/kg/day in Nifty cup group versus 17 ± 5 g/kg/day in paladai cup group, p = 0.18). Adverse events did not differ (32.9% in group A versus 27.1% in group B, p = 0.580). Nurses did not find any difference in ease of teaching caregivers [median (IQR) Nifty cup group 4(4,5) versus paladai cup group 4(4,5), p = 0.13]. Conclusion: The efficacy and adverse event rates were similar between Nifty cup feeding and paladai cup feeding in preterm infants. Both feeding modalities can be used prior to transition to direct breastfeeding in preterm low-birth-weight infants.

Congenital brain tumour in a neonate: a therapeutic challenge.

A term neonate with history of ventriculomegaly in the fetal period was diagnosed with a central nervous system tumour after radiological investigations. It was confirmed as an immature teratoma after histopathological examination. He underwent left frontal craniotomy with tumour excision. Intraoperatively, massive haemorrhage (venous bleed) occurred due to the high vascularity of the tumour and led to haemodynamic instability. A massive transfusion protocol was initiated. Despite multiple transfusions and shock management, he succumbed at 2 weeks of life. This case report highlights the importance of antenatal diagnosis and fetal MRI in prognostication and also the possible role of neoadjuvant chemotherapy in reducing tumour vascularity and, hence, bleeding.

Fluid and Parenteral Nutrition Practices in Extreme Preterm Neonates Among Neonatology Practitioners in India: A Web-based Survey.

An online survey pertinent to fluid and parenteral nutrition practices in extreme preterm neonates was undertaken with responses from 123 neonatology practitioners across India. The initial fluid rate of 80 mL/kg/day was preferred by 67% neonatologists for 750-1000 g neonates. Half of them increased the fluid rates when weight loss per day was >2%. Practices vary widely across settings and guideline tailor made to clinical conditions is needed.

Comparison of Ultrasound-Guided Umbilical Venous Catheter Insertion with Blind Method: A Randomized Controlled Trial.

Introduction: Ultrasonography (USG) can be used in neonates to manipulate and place the umbilical catheter in the correct position. Although chest radiograph (CXR) is the gold standard, a noninvasive method like USG without radiation exposure may be an alternative bedside armamentarium to the clinician. The purpose of the study was to evaluate whether USG-guided umbilical venous catheter (UVC) insertion is superior to the conventional method for the successful insertion of UVC. Method: The neonates born between 25 and 42 weeks of gestation requiring parenteral fluids and admission to neonatal intensive care unit (NICU) between September 2020 and November 2022 were randomized in two weight-based strata: ≤1,200 and >1,200 g. USG-guided UVC insertion was done in the intervention group and blind UVC insertion was done in the control group. Results: Out of 112 enrolled neonates, 58 were in the USG-guided group and 54 in the blind group. There was no significant difference in the failure rate between the intervention and control groups (20% versus 29% [RR: 0.69, 95% CI: 0.36-1.33]). The sensitivity and specificity of USG in locating tip position were 97 and 46.8%, respectively. The mean procedure time in USG and blind groups was 8.9 and 8.3 min, respectively (p value 0.56). Conclusion: USG does not reduce the failure rates during the insertion of umbilical catheters. However, being a safe, noninvasive procedure, it can be considered a rescue modality to CXR in NICUs equipped with portable USG for guiding UVC insertion.

Elizabethkingia meningoseptica Outbreak in NICU: An Observational Study on a Debilitating Neuroinfection in Neonates.

BACKGROUND: Elizabethkingia meningoseptica is an emerging nosocomial pathogen implicated in neonatal sepsis with high mortality and morbidities. However, there is very limited data regarding the characteristics as well as outcomes following this infection, particularly in developing countries. METHODS: We conducted a retrospective observational study of all infants with culture-positive Elizabethkingia sepsis as part of an outbreak, to study their clinical and epidemiological characteristics, as well as their antimicrobial susceptibility patterns, using a structured proforma from the neonatal intensive care unit database. Analysis was done using descriptive statistics and predictors of mortality and hydrocephalus were also identified. RESULTS: Of the 21 neonates enrolled, 9 (42.9%) were male, with a mean gestational age and birth weight of 31.7 ± 3.4 weeks and 1320 ± 364 g, respectively. The median (interquartile range) age of onset of illness was 7 (5-12) days. The overall mortality rate was 23.8%, and among survivors, 50% had neurologic complications requiring intervention. Vancomycin and ciprofloxacin were the most used antibiotics for treatment in our series, with a median duration of 26 (17-38) days. On univariate analysis, shock at presentation was significantly associated with increased mortality (P = 0.04) while, seizures (P = 0.04) and elevated cerebrospinal fluid protein levels (P = 0 .01) at onset of illness predicted progressive hydrocephalus in surviving neonates. CONCLUSION: E. meningoseptica sepsis is associated with high morbidity and mortality. Early diagnosis and prompt initiation of appropriate antibiotics are critical for improving survival and neurodevelopmental outcomes. Though isolation of the organism by environmental surveillance is always not possible, with proper infection control measures, the infection can be controlled.

Delayed cord clamping versus cord milking in vigorous neonates ≥35 weeks gestation born via cesarean: A Randomized clinical trial.

BACKGROUND: Delayed cord clamping (DCC) is the recommended strategy in neonates not requiring resuscitation, but umbilical cord milking (UCM) can also be used in term babies. DCC has been found to offer advantages more than just placental transfusion. OBJECTIVE: To compare the neonatal outcomes of DCC and UCM at birth in vigorous neonates ≥35 weeks born via cesarean section. METHODS: We included all vigorous neonates born ≥35 weeks of gestation through the cesarean section in this open-label randomized controlled trial. They were randomized into Group-A (DCC-cord was clamped 60 s after birth) or Group B(UCM). For neonates in Group B, the intact cord was milked at 25 cm from the stump 3 times towards the neonate and then clamped. The primary outcome was hematocrit at 72 h of life. Secondary outcomes were serum ferritin between 6 and 10 weeks of life, serum bilirubin at 72 h of life, need and duration of phototherapy, respiratory distress, hypoglycemia, hypotension, and sepsis. RESULTS: Baseline characteristics were similar in both the groups. The mean hematocrit at 72 h was more in the DCC group compared to the UCM group [(55.60±4.50) vs (53.89±4.44), MD (95% CI) = 1.71 (0.26, 3.16); p = 0.021]. There was no significant difference in median serum ferritin between the groups [102.88(84.67-173.24) vs 137.93(85.15-230.40); p = 0.173]. There was no significant difference in clinical outcomes. CONCLUSION: In neonates born via cesarean section, DCC resulted in improved hematocrit levels by 72 hours compared to UCM. DCC results in better placental transfusion.

COVID-19 pandemic and lockdown: impact on parents' stress level and infant care in a tertiary neonatal unit.

Neonatal intensive care unit (NICU) admission increases parents' stress levels and it might be even higher in the crisis of coronavirus disease 2019 (COVID-19) pandemic and lockdown. This study was done to identify the stress levels of parents of admitted neonates and the difficulties encountered in neonatal care and follow-up during the COVID-19 pandemic and lockdown. The Parental Stressor Scale (PSS:NICU) and Perceived Stress Scale (PeSS) were used to identify the stress levels of parents of admitted neonates. Online survey form with a structured questionnaire comprising PeSS and NICU:PSS was sent through messaging app (Google form) after informed consent. PSS score of <14 was considered low stress, 14-26 moderate and >26 as high. A total of 118 parental responses (mother /father in 26, both in 46) for 72 admitted neonates, were obtained. The mean (SD) PeSS score was 19.7 (5.8%) and 92 (78%) had moderate stress while 11 (9%) had high stress. In NICU:PSS, sights-sounds and parental role had more median scores: 2.25 (1-3.75) and 2.21 (1-3.57), respectively. Maternal and paternal NICU:PSS (p-0.67) and PeSS (p-0.056) scores were not statistically different. Keeping nil per oral, invasive ventilation, culture-positive sepsis, fathers' transport difficulty and longer duration of mothers' and neonates' hospital stay was associated with increased NICU: PSS scores. Twenty (29%) parents could not bring their child for follow-up and there was a delay in immunisation in 21 (30%). The pandemic and the lockdown might have disrupted antenatal and postnatal follow-ups further adding to the parental stress.

Infrahyoid Thyroglossal Duct Cyst Causing Airway Compromise in a Neonate: Surgical Management and Review of Literature.

Thyroglossal duct cyst (TGDC) rarely becomes symptomatic in the neonatal period unlike other congenital neck swellings which present with high airway obstruction. An infrahyoid TGDC presenting with airway compromise in a neonate is even rarer. We hereby report a newborn with significant respiratory distress necessitating intubation and ventilation since birth. He had multiple extubation failures and signs of upper airway obstruction post-extubation. Computed tomography demonstrated a cystic lesion, probably an infrahyoid TGDC compressing the laryngeal lumen. The cyst was removed by Sistrunk procedure and histopathology confirmed the diagnosis. The child was discharged 5 days after surgery and was asymptomatic on follow-ups.

Family Accommodation in Obsessive Compulsive Disorder and Its Association With Insight.

Background: Family accommodation (FA) is defined as a family members' involvement by doing certain behavior in response to the daily rituals of patients with obsessive-compulsive disorder (OCD). FA is associated with more severe symptoms of OCD. Similarly, poor insight is associated with high severity of OCD symptoms. FA and insight are also related to each other, as more accommodative behavior of family members is associated with poor insight. Methods: This cross-sectional observational study assessed 103 adult OCD patients with an illness duration of at least one year. Participants were assessed using Yale-Brown Obsessive Compulsive Scale (Y-BOCS) symptom checklist, Y-BOCS to assess severity, and Family Accommodation Scale-SR (Hindi) to evaluate FA. Insight was assessed with the 11th item of Y-BOCS. Results: FA was common in the families of our participants. The mean±SD Y-BOCS score was 28.72±5.09, and the mean FAS-SR score was 44.1±12.03. A significant positive correlation existed between the FA and YBOCS scores, that is, with the increase in FA, YBOCS scores also significantly increased. A considerable number reported poor insight, and had high scores on YBOCS and their caregiver had high FA scores. Conclusion: FA is indicative of high symptom severity of OCD and higher FA is associated with poor insight, so FA needs further research for its interplay with OCD symptomatology and role in the maintenance of symptoms.

Hypocarbia is associated with adverse outcomes in hypoxic ischaemic encephalopathy (HIE).

AIM: Hypocarbia in the early postnatal period might exacerbate brain injury in babies with hypoxic ischaemic encephalopathy following birth asphyxia. This mini-review summarised studies on pCO2 values that were monitored periodically in term newborns with moderate/severe hypoxic-ischaemic encephalopathy and correlated with short or long-term outcomes. METHODS: We searched the databases MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), web of science and the Cochrane Library and identified nine studies. RESULTS: Among the nine included studies, therapeutic hypothermia was administered in seven studies. In most studies, blood pCO2 levels were measured from birth till 72 h of life or till the endpoint of therapeutic hypothermia. Eight studies showed that any hypocarbia (moderate or severe, or cumulative) was associated with an increased risk of adverse outcomes in the form of brain injury in MRI, death or neurodevelopmental disability. CONCLUSION: Hypocarbia could lead to adverse short-term and long-term outcomes despite therapeutic hypothermia in neonates with HIE. Hence, it is vital to monitor pCO2 levels closely in these infants and consider strategies to maintain pCO2 levels in the normal range.

Three Different Regimens for Vitamin K Birth Prophylaxis in Infants Born Preterm: A Randomized Clinical Trial.

OBJECTIVE: To study the efficacy of 3 different vitamin K birth prophylaxis regimens in infants born premature. STUDY DESIGN: This was an open-label, parallel-group, randomized clinical trial conducted in a tertiary neonatal care unit in India. Infants born very preterm (≤32 weeks) and/or with very low birth weight (≤1500 g) were included. In each arm, 25 babies were enrolled. Babies were randomized to receive 1.0 mg, 0.5 mg, or 0.3 mg intramuscular (IM) vitamin K1 at birth. Protein induced by vitamin K absence - II (PIVKA-II) levels were assessed at birth, and on days 5 and 28, along with the frequency of death, bleeding manifestations, intraventricular hemorrhage, necrotizing enterocolitis, bilirubin levels, and duration of phototherapy. The primary outcome was comparison of PIVKA-II levels on day 5 of life. RESULTS: All the 3 regimens resulted in similar proportion of vitamin K subclinical sufficiency (PIVKA-II < 0.028 AU/mL) infants on day 5 (1 mg - 100%; 0.5 mg - 91.7%; 0.3 mg - 91.7%, P = .347), with no significant difference in median (IQR) PIVKA-II levels (AU/mL): 1 mg 0.006 (0.004, 0.009); 0.5 mg 0.008 (0.004, 0.009); 0.3 mg 0.006 (0.003, 0.009), P = .301. However, on day 28, there was a significant decrease in the proportion of vitamin K-sufficient infants in the 0.3-mg IM group (72.7%) compared with the 1.0-mg (100%) or 0.5-mg (91.3) groups. The 1.0-mg group had significantly greater bilirubin levels and duration of phototherapy. None of the other clinical outcomes were statistically different. CONCLUSIONS: Both 1-mg and 0.5-mg IM vitamin K birth prophylaxis resulted in high sufficiency on follow-up, compared with 0.3 mg. The current recommendation of 0.5-1 mg IM vitamin K birth prophylaxis for infants born preterm, needs to be continued. TRIAL REGISTRATION: CTRI/2022/02/040396.

Bovine milk-based and human milk-based fortification for postnatal weight gain in very preterm neonates-a cohort study.

BACKGROUND AND OBJECTIVES: Postnatal growth failure happens in about half of the very low birth weight infants and this can have long-term consequences. Human milk-based multi-nutrient fortifiers (HMBF) are thought to be better tolerated than bovine milk-based multi-nutrient fortifiers (BMBF), thus facilitating early progression to full feeds and improved growth in preterm neonates. This study was done to find the advantage of HMBF over BMBF on postnatal growth and other clinical outcomes. METHODS: This is a retrospective cohort study where babies <1500 g birth weight or gestational age <32 weeks were included to compare the velocity of weight gain (g/kg/day), duration of hospital stay and clinical outcomes between fortification using HMBF and BMBF till 34 weeks postmenstrual age. RESULTS: Eligible neonates included in the study were 322, out of whom 123 (37%) received HMBF and 209 (63%) received BMBF. During the stay, 18 babies were changed from BMBF to HMBF and vice versa in 24 babies due to logistic reasons and parents' preferences. The mean birth weight of the babies was 1124 ± 237 g. Weight gain was higher in the exclusive HMBF group [mean difference 0.77 (0.14, 1.39) g/kg/day; p-value = 0.018]. Feed intolerance [odds ratio (OR) 0.45 (0.22, 0.95), p-value 0.037] was also significantly less in this group. However, other morbidities did not differ significantly between the groups. CONCLUSION: Higher weight gain and lower feed intolerance in the HMBF group underscores the possible advantage of using HMBF over BMBF. Larger prospective studies might bring out its effect on the duration of hospital stay and other morbidities.

Case of iatrogenic neonatal acute kidney injury requiring dialysis and review of literature.

A full-term male baby was administered furosemide and enalapril for treatment of cardiac failure secondary to a ventricular septal defect. He also received piperacillin-tazobactam and amikacin for 7 days for suspected early-onset neonatal sepsis. He developed anuria and raised creatinine and was referred with acute kidney injury (AKI)-neonatal KDIGO (Kidney Disease Improving Global Outcomes) stage 3 on day 20. Urine output and renal parameters improved after discontinuing drugs and peritoneal dialysis. This case report highlights the importance of serial monitoring of kidney function tests while using nephrotoxic drugs and ensuring correct dosage and titration. In the early stages, AKI can be treated with conservative therapy but once established, renal replacement therapy might be required. It can also lead to chronic kidney disease.

Determination of Predictors of Brain Injury in Very Preterm Infants - A Retrospective Cohort Study.

Background: Despite decades of research, there is inadequate evidence on the etiological factors of brain injury in preterm infants. Objective: To study the perinatal risk factors for preterm brain injury and to assess their strength of association. Methods: In this retrospective cohort study, we included infants born at <32 weeks' gestation and had either magnetic resonance imaging (MRI) or cranial ultrasound (CUS) performed at term equivalent age. Significant brain injury was diagnosed based on Kidokoro global brain injury score was ≥4 in MRI or cystic periventricular leukomalacia in CUS. Results: Among the 698 infants, 48 had significant brain injury and 650 were taken as controls. In multiple logistic regression, intraventricular hemorrhage (IVH) grade 3-4 [adjusted odds ratio, 92.892 (19.495-442.619)], culture-positive sepsis [4.162 (1.729-10.021)], prolonged ventilation [3.688 (1.087-12.510)], and small for gestational age (SGA) [2.645 (1.181-5.924] were associated with greater risk of preterm brain injury. Conclusion: Severe IVH, culture-positive sepsis, prolonged ventilation and SGA were significant risk factors for preterm brain injury with severe IVH being the most significant contributing factor.

Clinical Profile, Outcomes and Predictors of Mortality in Neonates Operated for Gastrointestinal Anomalies in a Tertiary Neonatal Care Unit- An Observational Study.

Background: Gastrointestinal (GI) malformations have varied short-term and long-term outcomes reported across various neonatal units in India. Methods: This descriptive study was done to study the clinical profile, outcomes and predictors of mortality in neonates operated for congenital GI malformations in a tertiary neonatal care unit in South India between years 2011 and 2020. Details were collected by retrospective review of the case sheets. Results: Total of 68 neonates were included with esophageal atresia (EA) in 10, infantile hypertrophic pyloric stenosis (IHPS) in 9, duodenal atresia (DA) in 10, ileal atresia in 8, jejunal atresia in 5, anorectal malformations (ARM) in 11, meconium ileus/peritonitis in 9, malrotation in 2, and Hirschsprung's disease (HD) in 4. Antenatal diagnosis was highest in DA (80%). Associated anomalies were maximum in EA (50%), the most common being vertebral, anal atresia, cardiac defects, tracheoesophageal fistula, renal and radial abnormalities, and limb abnormalities association (VACTERL). Overall mortality was 15%. IHPS, DA, Malrotation, HD and ARM had 100 % survival while ileal atresia had the least survival (38%). Gestational age <32 weeks (odds ratio [OR] 12.77 [1.96, 82.89]) and outborn babies (OR 5.55 [1.01, 30.33]) were significant predictors of mortality in babies operated for small intestinal anomalies. None of the surviving infants were moderately or severely underweight at follow-up. Conclusion: Overall survival of surgically correctable GI anomalies is good. Among the predictors for mortality, modifiable factors such as in-utero referral of antenatally diagnosed congenital anomalies need attention. One-fifth had associated anomalies highlighting the need to actively look for the same. Although these neonates are vulnerable for growth failure, they had optimal growth on follow-up possibly due to standardized total parenteral nutritional policy during neonatal intensive care unit stay.

Predicting Significant Hyperbilirubinemia in ABO Incompatibility: Is Cord Direct Antiglobulin Test Useful?

To study the prevalence of direct antiglobulin test (DAT) positivity and outcomes in babies with ABO incompatibility and the role of DAT in predicting need for phototherapy. This was an analytical retrospective cohort study conducted in a tertiary care hospital in South India. DAT was performed routinely in cord blood of all neonates born to O positive mothers. The case records of neonates ≥ 35 weeks of gestation and birth weight > 2000 gm with ABO setting born between January 2019 and December 2020 were reviewed and outcomes were analyzed. Among 2484 live births, there were 426 eligible ABO incompatible births and DAT was positive in 68(15.9%). DAT positive neonates had significantly higher peak mean bilirubin [16.02 mg/dL vs. 13.68 mg/dL, p = 0.00], need for phototherapy in first 24 h [23(33.8%) vs. 32(8.9%), p = 0.00], need for exchange transfusion [2(2.9%) vs. 0(0%), p = 0.025] and immunoglobulin [6(8.8%) vs. 0(0%), p = 0.00]. Cord DAT showed 29.9% sensitivity, 96.9% specificity, 89.7% positive predictive value and 60.1% negative predictive value for predicting need for phototherapy. DAT positivity occurs in a significant proportion of ABO incompatible births and a "selective" cord blood DAT in neonates born to O positive mothers can identify those neonates at risk of significant hyperbilirubinemia with high diagnostic accuracy.

Dextrose Gel for Neonates at Risk With Asymptomatic Hypoglycemia: A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Hypoglycemia occurs in 5% to 15% of neonates in the first few days. A significant proportion requires admission for intravenous fluids. Dextrose gel may reduce admissions and mother-infant separation. We aimed to study the utility of dextrose gel in reducing the need for intravenous fluids. METHODS: This stratified randomized control trial included at-risk infants with asymptomatic hypoglycemia. Study populations were stratified into 3 categories: small for gestational age (SGA) and intrauterine growth-restriction (IUGR), infants of diabetic mothers (IDM) and large for gestational age (LGA), and late preterm (LPT) neonates. Intervention group received dextrose gel followed by breastfeeding, and the control group (CG) received only breastfeeding. RESULTS: Among 629 at-risk infants, 291 (46%) developed asymptomatic hypoglycemia; 147 (50.4%) in the dextrose gel group (DGG) and 144 (49.6%) in CG. There were 97, 98, and 96 infants in SGA/IUGR, IDM/LGA, and LPT categories, respectively. Treatment failure in the DGG was 17 (11.5%) compared to 58 (40.2%) in CG, with a risk ratio of 0.28 (95% confidence interval [CI]: 0.17-0.46; P < .001). Treatment failure was significantly less in DGG in all 3 categories: SGA/IUGR, IDM/LGA, and LPT with a risk ratio of 0.29 (95% CI:0.13-0.67), 0.31 (95% CI:0.14-0.66) and 0.24 (95% CI:0.09-0.66), respectively. CONCLUSIONS: Dextrose gel reduces the need for intravenous fluids in at-risk neonates with asymptomatic hypoglycemia in the first 48 hours of life.