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.

Autologous umbilical cord blood for red cell concentrate transfusion in preterm infants in the era of delayed cord clamping: An uncontrolled clinical trial.

OBJECTIVE: To assess the utility of autologous umbilical cord blood (UCB) for red cell concentrate (RCC) transfusion in preterm infants. METHODS: We recruited preterm infants born at ≤30 weeks' gestation or have an estimated fetal weight <1,200 g. We intended to perform delayed cord clamping (DCC) and to collect UCB following DCC. The quality parameters used included blood culture performed once, and biochemical and haematological parameters assessed weekly. RESULTS: Of the 46 recruited neonates, DCC could be performed for 1 minute in 11 (23.9%) and for 30-59 seconds in 10 (21.7%) infants. The success rate of UCB collection was significantly lower in infants who underwent DCC for 1 minute (27%) compared to those who underwent DCC for 30-59 seconds (70%) or immediate cord clamping (72%) (p value 0.031). Twenty-five UCBs were stored after eliminating three that had positive culture. UCB had satisfactory quality for transfusion from day 3 (when blood culture report was available) to 14 (after which pH decreased to <6.5). Thirteen infants required 27 RCC transfusions. Autologous UCB could be used for only five (18.5%) transfusions. CONCLUSION: The success rate of UCB collection after DCC for 1 minute is low. Autologous UCB meets less than one-fifth of transfusion requirements. Hence, autologous UCB transfusion is not a workable option in preterm infants.

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.

Diagnosis of a floppy neonate with misleading clues: unraveled as congenital hypomyelinating neuropathy.

Contactin-associated protein 1 (CNTNAP1)-related congenital hypomyelinating neuropathy (CHN) is a rare type of peripheral neuropathy and has a clinically heterogeneous presentation. We report a neonate with an atypical presentation in the form of global hypotonia, facial diparesis and partial response to neostigmine challenge test. There was no clinical improvement on initiation of anticholinesterase drug for suspected congenital myasthenia and hence stopped. Detection of a pathogenic variant in CNTNAP1 gene by clinical exome sequencing and subsequent reverse phenotyping confirmed CHN as the aetiology for this floppy neonate, which is known to have high mortality. The baby was given supportive care and she succumbed secondary to complications of prolonged ventilation.

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.

Early calcium and phosphorus supplementation in VLBW infants to reduce metabolic bone disease of prematurity: a quality improvement initiative.

OBJECTIVE: To reduce the incidence of metabolic bone disease (MBD) among very low birthweight (VLBW) infants admitted to neonatal intensive care unit from baseline of 35% by 50% over 2 years by implementing a quality improvement (QI) initiative. METHODS: A multidisciplinary QI team used evidence-based interventions and the healthcare improvement model to reduce MBD rate in VLBW infants. The specific interventions included routine enteral supplementation of calcium and phosphorus using Human Milk Fortifier (HMF) to expressed breast milk by day 14 of life (Plan/Do/Study/Act (PDSA) cycle 1), parenteral and early enteral supplementation of calcium and phosphorus (PDSA cycles 2 and 3). We included VLBW infants admitted within the study period at birth and excluded babies with congenital malformations, skeletal disorders and those who died before 2 weeks of age. Compliance with adding HMF by day 14, compliance with adding calcium and phosphorus in total parenteral nutrition (TPN) from day 1 of life and compliance with starting HMF when the baby reached 100 mL/kg/day of feeds were used as process indicators. The incidence of MBD was used as an outcome indicator during the study. The incidence of MBD was tracked using the Statistical Process Control methodology. RESULTS: The baseline MBD rate in 2015 was 35%. After the first PDSA cycle, 20% developed MBD (p=0.02). The same was sustained for a period of 1 year with the rate of 22%. After the second and third PDSA cycles, there was a drop in the MBD rate to 17%, and sustained for 3 months with 21%. CONCLUSION: Implementation of QI initiatives decreased the MBD rate from 35% to <20%. Early parenteral calcium and phosphorus supplementation in TPN and optimising enteral supplementation with multicomponent fortifiers appear to have significant reduction in the incidence of MBD.

Outcome of Inherited Metabolic Disorders Presenting in the Neonatal Period.

OBJECTIVE: To assess the outcome of infants who were diagnosed to have Inborn errors of metabolism (IEM) during neonatal period from a single center in South India. METHODS: This retrospective cohort study included consecutive neonates diagnosed to have IEM by biochemical testing or those detected using newborn screening (NBS) between November 2014 and July 2018. Disorders were categorized into intoxication and non-intoxication groups. Their presentation and outcome were described. Development at 12 mo was assessed objectively using DASII (Developmental assessment scale for Indian infants). Developmental quotient <70 was considered as delay. Mortality was analyzed using Kaplan Meier survival analysis. RESULTS: Among the total of 33 (14 intoxication and 19 non-intoxication groups), 7 died in neonatal period, 3 were lost to follow-up, 9 expired during varying period leaving 14 under regular follow-up. NBS detected 3 of them, others presented symptomatically unwell during neonatal period. Median survival was 18 mo (95% CI 3.7 to 32.2). Kaplan Meier survival analysis revealed a significant difference in mortality in intoxication compared to non-intoxication group. Among 14 survivors, 7 (50%) had developmental delay; 5 (35%) had seizures; 6 (43%) had growth failure. Infants with encephalopathy as initial presentation had poorer prognosis. NBS detection rate was 1 in 1060 live births (3 positives out of 3180 NBS samples). Those detected by NBS remained well. CONCLUSIONS: Morbidity and mortality remain high in those diagnosed as IEM during neonatal period. Despite the small sample size, this study calls attention to implement NBS wherever feasible.

Candida auris, an emerging pathogen - Challenge in the survival of microprimies.

Clinical profile of extreme preterm neonates and more so, of microprimies with birth weight < 800 g is not studied till now. Our article elaborates the profile of 5 microprimies with C.auris sepsis and review of literature. The mean gestational age and birth weight were 26 weeks ± 5 days and 709 ±â€¯64 g respectively. Mortality was 80%. The organism was susceptible to micafungin, voriconazole but was resistant to fluconazole and amphotericin. Among the 5 babies, one had organ involvement in the form of cardiac vegetation. Early identification and optimal choice of drug are crucial for better survival in C.auris sepsis.

Utility of clinical exome sequencing in the evaluation of neonates with suspected genetic condition - An observational study from tertiary neonatal care unit in South India.

OBJECTIVES: To study the utility of clinical exome sequencing (CES) using next generation sequencing (NGS) in evaluating neonates with suspected genetic conditions. METHODS: This is an observational study conducted in a tertiary care neonatal unit. We included neonates with suspected genetic conditions, for whom CES were done either by direct sampling or from stored DNA. Data was collected from the Sri Ramachandra centre of excellence in perinatal health (SCOPE) case records of 2016-2019. Yield of CES, percentage of pathogenic, non-pathogenic and variant of uncertain significance (VUS) and associated disorders were studied. RESULTS: CES was done in 36 neonates. Variants were detected in 78% (28/36). However, significant variants with clinical correlation were present in 20 (56%) babies. Test was carried out from the stored sample in 10 (28%) babies. Mean turn-around time was 39 ± 7 days. Specialist was involved in 1 and treatment changes were done in 5 neonates. Five out of 8 VUS were clinically correlating. Inborn errors of metabolism were the commonest (60%). Two VUS were ascertained as likely pathogenic after parental segregation analysis. CONCLUSION: CES has a definite role in evaluation of suspected genetic conditions for diagnosis and prognostication. It also helps scientific society to build in additional evidence so that the "VUS" could be asserted as "likely pathogenic" . Our experience reiterates the importance of storing and archiving DNA of the affected child.

Disposable low-cost cardboard incubator for thermoregulation of stable preterm infant - a randomized controlled non-inferiority trial.

BACKGROUND: Incubators and radiant warmers are essential equipment in neonatal care, but the typical 1,500 to 35,000 USD cost per device makes it unaffordable for many units in low and middle-income countries. We aimed to determine whether stable preterm infants could maintain thermoregulation for 48 h in a low-cost incubator (LCI). METHODS: The LCI was constructed using a servo-heater costing 200 USD and cardboard infant-chamber. We conducted this open-labeled non-inferiority randomized controlled trial in a tertiary level teaching hospital in India from May 2017 to March 2018. Preterm infants on full feeds and receiving incubator or radiant warmer care were enrolled at 32 to 36 weeks post-menstrual age. We enrolled 96 infants in two strata (Strata-1< 33 weeks, Strata-2 ≥ 33 weeks at birth). Infants were randomized to LCI or standard single-wall incubator (SSI) after negative incubator cultures and monitored for 48 h in air-mode along with kangaroo mother care. The incubator temperature was adjusted manually to maintain skin and axillary temperatures between 36.5 °C and 37.5 °C. During post-infant period after 48 h, SSI and LCI worked for 5 days and incubator temperatures were measured. The primary outcome was maintenance of skin and axillary temperatures with a non-inferiority margin of 0.2 °C. Failed thermoregulation was defined as abnormal axillary temperature (< 36.5 °C or >37.5 °C) for > 30 continuous-minutes. Secondary outcomes were incidence of hypothermia and required incubator temperature. Trial registration details: Clinical Trial Registry - India (CTRI/2015/10/006316). FINDINGS: Prior to enrollment 79(82%) infants were in radiant warmer and 17(18%) infants were in incubator care. Median weight at enrollment in Strata-1 and Strata-2 for SSI vs. LCI was 1355(IQR 1250-1468) vs. 1415(IQR 1280-1582) and 1993(IQR 1595-2160) vs. 1995(IQR 1632-2237) grams. Mean skin temperature in Strata-1 and Strata-2 for SSI vs. LCI was 36.8 °C ± 0.2 vs. 36.7 °C ± 0.18 and 36.8 °C ± 0.22 vs. 36.7 °C ± 0.19. Mean axillary temperature in Strata-1 and Strata-2 for SSI vs. LCI was 36.9 °C ± 0.19 vs. 36.8 °C ± 0.16 and 36.8 °C ± 0.2 vs. 36.8 °C ± 0.19. Mixed-effect model done for repeated measures of skin and axillary temperatures showed the estimates were within the non-inferiority limit; -0.07 °C (95% CI -0.11 to -0.04) and -0.06 °C (95% CI -0.095 to -0.02), respectively. Failed thermoregulation did not occur in any infants. Mild hypothermia occurred in 11 of 48(23%) of SSI and 16 of 48(33%) of LCI, OR 1.28 (95%CI 0.85 to 1.91). Incubator temperature in LCI was higher by 0.7 °C (95%CI 0.52 to 0.91). In the post-infant period SSI and LCI had excellent reliability to maintain set-temperature with intra-class correlation coefficient of 0.93 (95%CI 0.92 to 0.94) and 0.96 (95%CI 0.96 to 0.97), respectively. INTERPRETATION: Maintenance of skin and axillary temperature of stable preterm infants in LCI along with kangaroo mother care was non-inferior to SSI, but at a higher incubator temperature by 0.7 °C. No adverse events occurred and LCI had excellent reliability to maintained set-temperature. FUNDING: Food and Drug Administration (Award number P50FD004895).

Impact of Lactation Support Program on Initiation of Breastfeeding in Term Infants.

Purpose: Early initiation of breastfeeding (EIBF) significantly decreases neonatal mortality and improves exclusive breastfeeding. The objective of the present study was to assess the effect of lactation support program (LSP) on early initiation of breastfeeding (BF) among term well infants. Methods: A "before-and-after" design was used to study the effect of the LSP on EIBF at a tertiary care institute in India over a period of two and half years. EIBF was defined as BF initiated <1 hour in vaginal delivery (VD) and <2 hours in cesarean section (CS). Impact of LSP was assessed by comparing baseline data (control group) with data after initiation of LSP (study group). Even after 1 year of initiation of LSP, EIBF in CS remained low, hence a hospital policy was implemented to alter a modifiable factor to promote EIBF in CS. Data of the study group was analyzed over two time periods, as study group A (prior to implementation of hospital policy) and study group B (following the commencement of hospital policy). Results: A total of 2,769 postnatal mothers were included for the study with 537 in the control group, 1,157 in study group A, and 1,075 in study group B. In VD, EIBF rate increased significantly from 92.6% at baseline to 99.8% and 99.6%, in study group A and study group B, respectively (p value < 0.001). In CS, EIBF rate increased from 0.4% at baseline to 1.9% and 92.7% in study group A and study group B, respectively (p < 0.001). The time of initiation of BF reduced from 1.3 (0.9) to 0.7 (0.3) hours in VD and from 4.2 (0.71) to 1.8 (0.66) hours in CS with both having a p value of < 0.001. Conclusion: Lactation support program is a simple but effective way of implementing appropriate steps towards promotion of exclusive BF.

Meconium Peritonitis: A Rare Treatable Cause of Non-Immune Hydrops.

Meconium peritonitis as a cause of non-immune hydrops in neonates is rarely reported. Here we report such a rare occurrence. In our case, a routine antenatal scan at 25 weeks revealed isolated ascites. By 31 weeks of gestation, all features of hydrops were observed in scans. However, antenatal workup for immune and non-immune hydrops was negative. Subsequently, a preterm hydropic female baby was delivered at 32 weeks. She required intubation and ventilator support. An X-ray revealed calcification in the abdomen suggestive of meconium peritonitis. Ultrasound showed gross ascites, a giant cyst compressing the inferior vena cava, and minimal bilateral pleural effusion. Emergency laparotomy revealed meconium pellets and perforation of the ileum. Double-barrel ileostomy was performed, and the edema resolved and activity improved. The baby was discharged after 3 weeks. Ileostomy closure was done at follow-up. The baby is growing well.

Continuous Temperature Monitoring Using Bluetooth- enabled Thermometer in Neonates.

We aimed to compare continuous temperature-monitoring using Bluetooth-enabled thermometer (BET) and intermittent monitoring by digital thermometer (DT) in neonates. Continuous monitoring using BET identified 377 episodes of hypo/hyperthermias in 90 baby-days; 316 (83.8%) episodes were confirmed by DT and 61 (16.2%) were false alarms. Five episodes were missed by BET. The agreement between digital thermometer and BET was good. Continuous temperature monitoring helps in early identification of hypo/hyperthermia in neonates.