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.

Aicardi-Goutières syndrome (AGS): recurrent fetal cardiomyopathy and pseudo-TORCH syndrome.

Aicardi-Goutières syndrome (AGS) induces innate immune activation. It can present with cerebral calcifications and hepatosplenomegaly mimicking congenital infections. The present case report discusses the diagnosis and treatment of a case of fetal cardiomyopathy whose postnatal symptoms resembled TORCH (toxoplasmosis, other agents, rubella, cytomegalovirus, herpes and syphilis) infection. The mother had a history of two lost pregnancies due to fetal cardiomyopathy and the same was identified in the current pregnancy. At 34 weeks of gestation, the mother delivered a late preterm male neonate due to intrauterine growth restriction weighing 1590 g with respiratory distress and cardiomyopathy at birth. The neonate had cerebral calcifications, hepatosplenomegaly and thrombocytopenia. As the infant's TORCH IgM titre was negative, pseudo-TORCH syndrome similar to AGS was suspected. Clinical exome sequencing of the parents and fetus identified no genes for hydrops fetalis or fetal cardiomyopathy; however, the AGS TREX1 gene was identified in the neonate, while additional symptoms resembled TORCH infection. The neonate was discharged and has shown improvement with oral baricitinib treatment for the last 9 months.

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.

Cow's milk protein allergy in a neonate presenting with methaemoglobinaemia.

Cow's milk protein allergy (CMPA) is the most common food allergy in infants. A previously healthy neonate fed with infant formula presented diarrhoea, vomiting and respiratory distress with cyanosis. Investigations showed thrombocytosis and leucocytosis with lymphocyte predominance. To our surprise blood gas analysis showed metabolic acidosis and a high methaemoglobin level of 33% (normal range <3%). Clinical status, metabolic acidosis and methaemoglobin level returned to normal following fluid resuscitation and methylene blue administration. The neonate was later managed with breast feeding and elemental formula. CMPA was diagnosed based on history and clinical improvement after elemental formula. Although not common in CMPA, methaemoglobinaemia should be recognised as a differential diagnosis in a hypoxic infant with metabolic acidosis and diarrhoea as early recognition and treatment with methylene blue can save a child's life.

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.

Hypoventilation and progressive encephalopathy in a neonate with MTHFR deficiency.

Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive inherited inborn error of metabolism, which presents with various severity depending on the level of residual enzyme activity. In neonates, it can present with recurrent hypoventilation episodes, persistent encephalopathy with or without microcephaly. MTHFR deficiency also results in hyperhomocysteinemia, homocystinuria and hypomethionemia. We report a male neonate with severe MTHFR deficiency presenting to us on third week of life with progressive encephalopathy, microcephaly, seizures, central hypoventilation. There was similar history in the previous sibling. The patient's blood lactate, ammonia, tandem mass spectrometry for amino acids and acyl carnitine were normal. He remained encephalopathic with progressive increase in need of respiratory support in spite of supportive treatment and metabolic cocktail consisting of riboflavin, pyridoxine, coenzyme Q and carnitine. This neonate had novel homozygous mutation, which results in MTHFR deficiency. In newborn with hypoventilation or recurrent apnoea with encephalopathy and microcephaly, MTHFR deficiency should be considered as a differential diagnosis. Mutation study helps in confirming diagnosis; however, extended newborn metabolic screening with homocysteine level could help in early diagnosis of these cases.

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.

Recent approaches in clinical applications of 3D printing in neonates and pediatrics.

Neonates and pediatric populations are vulnerable subjects in terms of health. Proper screening and early optimal treatment would reduce infant and child mortality, improving the quality of life. Researchers and clinicians all over the world are in pursuit of innovations to improve the medical care delivery system. Infant morphometrics changes drastically due to the rapid somatic growth in infancy and childhood, demanding for patient-specific customization of treatment intervention accordingly. 3D printing is a radical technology that allows the generation of physical 3D products from digital images and addresses the patient-specific requirement. The combination of cost-effective and on-demand customization offers a boundless opportunity for the enhancement of neonates and pediatric health.Conclusion: The advanced technology of 3D printing proposes a pioneering breakthrough in bringing physiologically and anatomically appropriate treatment strategies addressing the unmet needs of child health problems. What is Known: • The potential application of 3D printing is observed across a multitude of fields within medicine and surgery. • The unprecedented effect of this technology on pediatric healthcare is still very much a work in progress. What is New: • The recent clinical applications of 3D printing provide better treatment modalities to infants and children. • The review provides an overview of the comparison between conventional treatment methods and 3DP regarding specific applications.

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.