Sirolimus in infants with congenital hyperinsulinism (CHI) - a single-centre experience.

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in neonates and infants. Medical treatment includes the use of high concentrations of glucose and combinations of diazoxide, octreotide and glucagon. We report our experience of using sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, in the treatment of CHI in seven newborns who are poorly responding to standard medical therapy. Majority (87%) of infants achieved euglycaemia using a combination of oral feeding and the addition of sirolimus to standard medical treatment. One infant who failed to achieve euglycaemia even after surgery managed successfully with sirolimus. Diagnosis was confirmed by genetics evaluation; in three infants, novel mutations were detected. Outcome and long-term follow-up of all cases are described.Conclusion: Sirolimus can be considered in treatment of CHI refractory to standard medical treatment or in cases unresponsive to surgical treatment. What is Known: • Congenital hyperinsulinism (CHI) or persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) associated with mutations such as the ABBC8 or KCNJ gene known to cause hypoglycaemia refractory to standard medical treatment such as diazoxide and octreotide and may need subtotal pancreatectomy (STP). • Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, was recently reported to be useful for refractory CHI cases with variable efficacy. What is New: • Our case series describes efficacy and safety of sirolimus in seven genetically proven refractory CHI cases with mainly neonatal presentation. All patients' follow-ups are described. • Out of seven infants, six infants responded well to sirolimus, and among these one infant who failed to respond to surgery (STP) also successfully managed with sirolimus. • It highlights the right patient selection and right dose to successfully manage these cases without much adverse effects.

High Frequency Oscillatory Ventilation (HFOV) and Inhaled Nitric Oxide (iNO) Use During Neonatal Emergency Transport - Feasibility and Efficacy in India.

A retrospective study of 24 neonates to evaluate the feasibility and efficacy of high frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (iNO) for transferring critically ill neonates to tertiary neonatal intensive care, who were transported by road ambulance was done. Efficacy was measured by clinical improvement, patient safety was assessed by comparing cardiorespiratory indicators before and after transport, and adverse events during transport. Significant oxygenation improvement was observed in neonates transported with HFOV ± iNO compared to earlier ventilator settings. Pre- and post-transport vital signs were stable, and no transport-related deaths occurred. A substantial rise in median SpO2 was seen after transfer [86 (81, 91) vs. 93 (89, 97) before transport, p <0.001]. Twelve of twenty-one newborns who received nitric oxide demonstrated significant improvement in oxygenation index (a 10% decrease from prior value). Overall survival was 70.8%, however non-transfer or inadequate respiratory treatment may have exacerbated mortality.

Human Milk-Derived Fortifier as Rescue Therapy in Very Preterm Infants Intolerant to Cow's Milk-Derived Fortifier.

This was a retrospective, descriptive study where human milk-derived fortifier (HMDF) was used to rescue infants intolerant to cow's milk-derived fortifier (CMDF). Rescue therapy was used for newborns with feed intolerance, systemic symptoms, or thrombocytosis. In a total of 412 very preterm infants (gestational age ≤ 32 wk) admitted to NICU during the study period, 14 infants met the rescue protocol inclusion criteria. The mean gestational age of these 14 infants was 29.2 ± 1.2 wk and birth weight was 1161 ± 201 g. All the infants who received rescue protocol by changing over to HMDF tolerated feeds well and showed a positive growth trend. Four infants had thrombocytosis, out of which 2 infants had elevated platelet count even with HMDF. Premature infants with intolerance to CMDF were effectively managed using HMDF as a rescue protocol. Infants tolerated HMDF well and showed positive growth trends till the discharge.

Pasteurized Donor Human Milk Should Not Replace Mother's Own Milk in Preterm Neonates: A Quality Initiative Toward Decreasing the "PDHM Dependency".

Aim: Mother's own milk (MOM) is the preferred source of neonatal nutrition. Due to various challenges, mothers are often unable to provide exclusive MOM to neonates admitted in neonatal intensive care units (NICUs) and depend on pasteurized donor human milk (PDHM). The aim of this quality improvement (QI) initiative was to enable mothers to provide MOM and consequently decrease the "PDHM dependency." Methods: Neonates <32 weeks of gestation (n = 120) were included. A multidisciplinary team was formed, and a detailed root cause analysis was done to understand the cause of PDHM dependency during the observation phase (November 1 to December 15, 2019). Various evidence-based practices were planned, tested, and implemented through Plan-Do-Study-Act cycles during the intervention phase (December 16, 2019 to January 31, 2020). These were further strengthened and adopted as a unit culture during the maintenance phase (February 1 to July 31, 2020). Results from the observation and intervention phases were compared. Results: Within 6 weeks of QI interventions, the average proportion of MOM significantly increased from 74.4% to 93.5% (p = 0.0003), and the proportion of PDHM significantly decreased from 20.5% to 4.6% (p = 0.005). The proportion of MOM remained at 82.5% during the maintenance phase. There was a significant decrease in the number of days to reach full feeds and regain birth weight. Conclusions: Provision of PDHM from our newly functional milk bank led to a reduced drive to express MOM in mothers of NICU babies. Our QI project focused on various strategies to improve MOM feeding and reduce PDHM dependence.

Diagnostic and Therapeutic Roles of the "Omics" in Hypoxic-Ischemic Encephalopathy in Neonates.

Perinatal asphyxia and neonatal encephalopathy remain major causes of neonatal mortality, despite the improved availability of diagnostic and therapeutic tools, contributing to neurological and intellectual disabilities worldwide. An approach using a combination of clinical data, neuroimaging, and biochemical parameters is the current strategy towards the improved diagnosis and prognosis of the outcome in neonatal hypoxic-ischemic encephalopathy (HIE) using bioengineering methods. Traditional biomarkers are of little use in this multifactorial and variable phenotype-presenting clinical condition. Novel systems of biology-based "omics" approaches (genomics, transcriptome proteomics, and metabolomics) may help to identify biomarkers associated with brain and other tissue injuries, predicting the disease severity in HIE. Biomarker studies using omics technologies will likely be a key feature of future neuroprotective treatment methods and will help to assess the successful treatment and long-term efficacy of the intervention. This article reviews the roles of different omics as biomarkers of HIE and outlines the existing knowledge of our current understanding of the clinical use of different omics molecules as novel neonatal brain injury biomarkers, which may lead to improved interventions related to the diagnostic and therapeutic aspects of HIE.

Quality improvement initiative to decrease extrauterine growth restriction in preterm neonates.

BACKGROUND: Prevention of extrauterine growth restriction (EUGR) in preterm neonates is one of the biggest challenges to neonatologists. Lack of uniformity and inconsistency in nutrition practices are the most common causes. We started a quality improvement (QI) initiative with an intention to decrease the proportion of EUGR. METHODS: We performed prospective nonrandomized QI from May 2018 to July 2019. Ninety-six neonates (born at <32 weeks and/or <1.2 kg) were compared with 111 historical controls. A continuous feedback loop was maintained, and changes were analyzed as plan-do-study-actcycle. RESULTS: Although EUGR was lower after the intervention (93.7% vs 87.5%), this change was not statistically significant. However, other measures of in-hospital neonatal growth showed improvement, including median discharge weight percentile from 1% to 3% (P = .003). Median difference in the z-score for weight from birth to discharge also improved significantly from -1.84 to -1.65 (P = .04). Babies in the intervention group regained birth weight earlier (P = .005) and had better growth velocity (P = .0005). The feeding was started early (P < .0001), and these babies reached full feeds (P < .0001) earlier than the control cohort. CONCLUSION: Although our QI initiative failed to achieve a significant reduction in EUGR, it did achieve a significant improvement in discharge weight percentile and difference in the z-score for weight at birth and during discharge from hospital. There was a significant improvement in growth velocity and an early regaining of birth weight. The implementation of written nutrition practice guidelines facilitated improved outcomes.

A Quality Initiative to Improve Mother's Own Milk Feeding in Preterm Neonates.

Background: The rates of "any" human milk use in neonatal intensive care units have improved during the last decade. However, efforts to help mothers in expressing and maintaining mother's own milk (MOM) through discharge remain a concern. This study aims to improve MOM in preterm neonates. Methods: The study was a quality improvement (QI) initiative conducted from May 2018 to April 2019. All preterm neonates <34 weeks were included. In the "initiation phase" (May 2018 to August 2018), a breastfeeding support group was formed and mothers were given structured antenatal and postnatal counseling regarding MOM using videos and leaflets. This improved MOM rates when compared with retrospective controls. In the continuation phase (August-2018 to April-2019), various plan-do-study-act cycles were conducted to test strategies such as frequent telephonic reminders, standardization of Kangaroo mother care, nonnutritive sucking protocols, and involving family members during daily counseling sessions. The initiation and continuation phases were compared with the retrospective baseline data. Results: Of a total of 125 preterm neonates, 27 were excluded for various reasons. Within 3 months of initiating the study, the proportion of neonates who received MOM within first 24 hours improved from 24% in retrospective controls to 82.9% in the initiation phase (p < 0.0001) and remained stable at 90.3% in the continuation phase. The amount of MOM received on day 1 increased significantly (p < 0.0001) from a median of 0 mL to 1 mL in the initiation phase and was maintained at 3 mL in the continuation phase. Amount of MOM increased significantly on day 3 (p = 0.0003) and day 7 (p = 0.03). Babies discharged on MOM also improved significantly (p = 0.005) from 48.3% in the retrospective cohort to 77.4% in the continuation phase. The number of babies receiving total parenteral nutrition decreased significantly (p = 0.02) from 54.6% to 26.7%. Conclusions: QI has shown promising results in improving MOM in preterm neonates.

Thiamine-Responsive Acute Pulmonary Hypertension of Early Infancy (TRAPHEI)-A Case Series and Clinical Review.

Persistent pulmonary hypertension of the newborn (PPHN) is a syndrome of high pulmonary vascular resistance (PVR) commonly seen all over the world in the immediate newborn period. Several case reports from India have recently described severe pulmonary hypertension among infants in the postneonatal period. These cases typically present with respiratory distress in 1-6-month-old infants, breastfed by mothers on a polished rice-based diet. Predisposing factors include respiratory tract infection such as acute laryngotracheobronchitis with change in voice, leading to pulmonary hypertension, right atrial and ventricular dilation, pulmonary edema and hepatomegaly. Mortality is high without specific therapy. Respiratory support, pulmonary vasodilator therapy, inotropes, diuretics and thiamine infusion have improved the outcome of these infants. This review outlines four typical patients with thiamine-responsive acute pulmonary hypertension of early infancy (TRAPHEI) due to thiamine deficiency and discusses pathophysiology, clinical features, diagnostic criteria and therapeutic options.

Mitochondrial carbonic anhydrase VA deficiency in three Indian infants manifesting early metabolic crisis.

BACKGROUND: Hyperammonemia and hyperlactatemia in neonates and young children with non-specific biochemical markers poses a diagnostic challenge. An accurate diagnosis is essential for effective management. CASE REPORTS: We present three infants from unrelated families, one with infantile and two with neonatal hyperammonemic encephalopathy, hypoglycaemia, and hyperlactatemia. The underlying cause was confirmed following whole exome sequencing as biochemical markers were not conclusive of a definite diagnosis. CONCLUSION: The combination of hyperammonemic encephalopathy, hyperlactatemia and hypoglycemia in neonates and infants should prompt physicians to suspect Carbonic anhydrase VA deficiency. Majority of these children can have a favourable long-term outcome with symptomatic treatment.

A quality initiative to improve exclusive breast milk feeding in preterm neonates.

BACKGROUND AND OBJECTIVE: Preterm babies thrive well on exclusive breastfeeding with fewer complications. In a retrospective analysis, challenges were noticed in the form of delayed first milk expression and frequency of expression, which was limited to 2-3 times a day. A quality improvement initiative was designed to increase the exclusive breast milk feeding rates in admitted preterm babies. The purpose of the present study is to evaluate the proportion of preterm neonates receiving mother's own milk by day 7 of life after such an initiative. METHODS: The quality improvement initiative was conducted at a level 3 neonatal intensive care unit from May 10, 2018, to August 10, 2018. Inborn preterm neonates <34 weeks with a minimum hospital stay of 7 days were included. Neonates of critically sick mothers and neonates having major congenital malformations were excluded. Mothers were given structured antenatal counseling regarding expressing breast milk (EBM). Postnatal visits were conducted to provide information through a video and a leaflet and formation of breastfeeding support group. RESULTS: A total of 30 babies were recruited during a period of 3 months and compared to historical controls. The median age of the first EBM improved from 2.5 days to 1.16 days, and the amount of EBM on the first day improved from 0.24 ml to 2.6 ml (p = .002). The proportion of babies receiving EBM on the first day improved from 24% to 80% (p = .0001), and at the end of 7 days, it increased to 73% from 46% (p = .02). The factors time to reach full enteral feeds, time to regain birth weight, rate of necrotizing enterocolitis, rate of sepsis, and proportion of babies on exclusive mother's milk during discharge appear comparable in both the groups. CONCLUSIONS: A simple quality improvement approach through the formation of breastfeeding support group, antenatal counseling, and postnatal support for breast milk expression has made a significant improvement in milk expression from mothers delivered prematurely. It reflects on a team approach using the available resources.

Papaverine for Ischemia Following Peripheral Arterial Catheterization in Neonates.

11 Extremely low birth weight neonates who developed skin discoloration after peripheral arterial catheterization were given intra-arterial papaverine before the removal of arterial line. The skin color turned normal in all these neonates and none developed residual damage. In 3 neonates who could not receive papaverine, one developed gangrene of fingers.

ATP-binding cassette transporter A3 (ABCA3) mutation in a late preterm with respiratory distress syndrome.

BACKGROUND: Surfactant protein abnormalities are rare causes of respiratory distress syndrome. CASE CHARACTERISTICS: A late preterm (36 wks) who presented with respiratory distress syndrome. OBSERVATION: He was found to be a homozygous for a G to T transversion at the first base in intron 24, of ABCA3 gene which is necessary for lamellar body formation and surfactant production. OUTCOME: He died of severe respiratory failure even after multiple doses of surfactants and ventilation. MESSAGE: Surfactant deficiency with ABCA3 gene mutation needs to be suspected in late preterms who present with respiratory distress syndrome.

Respiratory flutter syndrome in a neonate.

Respiratory flutter or diaphragmatic flutter is a rare disorder characterized by involuntary, high frequency contractions of the diaphragm. Only 7 cases are reported in infants till date. The present case presented with life threatening respiratory distress immediately after birth. In view of high respiratory rate of 120-154 per minute, clinical and fluoroscopic evidence of diaphragmatic contraction and absence of any obvious CNS, cardiovascular and respiratory pathology, respiratory flutter was diagnosed. It was also associated with dysphagia and laryngomalacia. The patient was managed with prolonged continuous positive airway pressures (CPAP) with partial success, but symptoms improved with use of chlorpromazine.

Congenital central hypoventilation syndrome with PHOX2B gene mutation.

A term baby developed hypoventilation on day 1 of life requiring mechanical ventilation and had subsequent difficulty in weaning. Diagnostic workup for pulmonary, cardiac, metabolic, sepsis and structural CNS diseases were negative. In view of persistent hypoventilation despite raised pCO(2) levels in absence of any sedation, the diagnosis of Idiopathic. Congenital Central Hypoventilation Syndrome (CCHS) was considered. The baby was tested for Paired-like Homeobox 2B (PHOX2B) gene mutation and was found to have expanded alleles containing 10 polyalanine repeats producing genotype of 20/30 on chromosome 4p12 (The normal being 20/20). This is the first report of a neonate from India with genetically confirmed CCHS.

Rescue high frequency oscillation in neonates with acute respiratory failure.

The aim was to study the efficacy of rescue High Frequency Oscillatory Ventilation (HFOV) in improving the oxygenation and ventilation in neonates with acute respiratory failure after failing Conventional Mechanical Ventilation (CMV). Primary outcome was short term oxygenation, lung recruitment, and ventilation and secondary outcome studied was survival. 675 babies were ventilated and 97 of them received HFOV. HFOV significantly improved oxygenation index, alveolar-arterial oxygen gradient, pH, PCO2, PO2 and caused better lung recruitment within 2 hours. Fifty seven babies (58.77%) survived and the mortality was more in <28 weeks, babies with pulmonary hemorrhage, sepsis and CDH.