Comparative Growth Outcomes in Very Low Birth Weight Infants: Evaluating Different Feeding Strategies.

OBJECTIVES: To assess the growth pattern of preterm, very low birth weight (VLBW) appropriate for gestational age (AGA) infants on three different feeding regimens. METHODS: This prospective open label three-arm parallel randomized controlled trial was conducted at neonatal intensive care unit, Kasturba Hospital, Manipal. One hundred twenty VLBW (weight between 1000-1500 g and gestational age 28-32 wk) preterm AGA infants admitted from April 2021 through September 2022 were included. Three feeding regimens were compared: Expressed breast milk (EBM); EBM supplemented with Human milk fortifier (HMF); EBM supplemented with Preterm formula feed (PTF). Primary outcome measure was assessing the growth parameters such as weight, length, head circumference on three different feeding regimens at birth 2, 3, 4, 5 and 6 wk/discharge. Secondary outcomes included incidence of co-morbidities and cost-effectiveness. RESULTS: Of 112 infants analyzed, Group 2 supplemented with HMF showed superior growth outcomes by 6th wk/discharge of intervention, with mean weight of 2053±251 g, mean length of 44.6±1.9 cm, and mean head circumference of 32.9±1.4 cm. However, infants in Group 3, supplemented with PTF, registered mean weight of 1968±203 g, mean length of 43.6±2.0 cm, and mean head circumference of 32.0±1.6 cm. Infants exclusively on EBM presented with mean weight of 1873±256 g, mean length of 43.0±2.0 cm and mean head circumference of 31.4±1.6 cm. CONCLUSIONS: Addition of 1 g of HMF to 25 ml of EBM in neonates weighing 1000-1500 g showed better weight gain and head circumference at 6 wk/discharge, which was statistically significant. However, no significant differences in these parameters were observed at postnatal or 2, 3, 4, and 5 wk.

Sustaining extended Kangaroo mother care in stable low birthweight babies in NICU: a quality improvement collaborative of six centres of Karnataka.

BACKGROUND: Kangaroo mother care (KMC) is a proven intervention for intact survival in preterms. Despite evidence, its adoption has been low. We used a point of care quality improvement (QI) approach to implement and sustain KMC in stable low birthweight babies from a baseline of 1.5 hours/baby/day to above 4 hours/baby/day through a series of plan-do-study-act (PDSA) cycles over a period of 53 weeks. METHODS: All babies with birth weight <2000 g not on any respiratory support or phototherapy and or umbilical lines were eligible. The key quantitative outcome was KMC hours/baby/day. A QI collaborative was formed between six centres of Karnataka mentored by a team with a previous QI experience on KMC. The potential barriers for extended KMC were evaluated using fishbone analysis. Baseline data were collected over 3 weeks. A bundled approach consisting of a variety of parent centric measures (such as staff awareness, making KMC an integral part of treatment order, foster KMC, awareness sessions to parents weekly, recognising KMC champions) was employed in multiple PDSA cycles. The data were aggregated biweekly and the teams shared their implementation experiences monthly. RESULTS: A total of 1443 parent-baby dyads were enrolled. The majority barriers were similar across the centres. Bundled approach incorporating foster KMC helped in the quick implementation of KMC even in outborns. Parental involvement and empowering nurses helped in sustaining KMC. Two centres had KMC rates above 10 hours/baby/day, while remaining four centres had KMC rates sustained above 6 hours/baby/day. Cross-learnings from team meetings helped to sustain efforts. Extended KMC could be implemented and sustained by low intensity training and QI collaboration. CONCLUSIONS: Formation of a QI collaborative with mentoring helped in scaling implementation of extended KMC. Extended KMC could be implemented by parent centric best practices in all the centres without any additional need of resources.

Effect of Therapeutic Hypothermia on the Outcome in Term Neonates with Hypoxic Ischemic Encephalopathy-A Randomized Controlled Trial.

OBJECTIVE: To assess the effect of therapeutic hypothermia on the outcome in term neonates with hypoxic ischemic encephalopathy (HIE). METHODS: A randomized controlled trial was conducted in a tertiary care teaching hospital in south India. Term infants with moderate to severe HIE were randomized to be treated with normothermia or hypothermia. Mortality, neurological abnormality or normal outcome was recorded at hospital discharge or 28 days of age, whichever was earlier, and at 18 months of age. RESULTS: The baseline maternal and neonatal characteristics in the two groups were similar. The 78 infants in the hypothermia group had more normal survivors at discharge (38%) than the 84 infants in the normothermia group (30%), ratio 1.29 (95% confidence interval 0.84-1.99), and at 18 months of age (65% vs. 42%), ratio 1.54 (1.13-2.10). When these results were combined with those of a previous randomized trial in the same neonatal unit, there were significantly more normal survivors with hypothermia compared to normothermia at discharge, ratio 1.49 (1.18-1.88) and at 6-18 months of age, ratio 1.37 (1.17-1.60). CONCLUSION: In term infants with HIE, therapeutic hypothermia reduced mortality and neurological abnormalities, and resulted in more normal survivors. LAY SUMMARY: Babies who do not breathe immediately after they are born are likely to die or have brain damage. Previous studies have suggested that cooling these babies after birth might reduce the number who die or have brain damage. In this resource-limited setting, babies who were cooled were less likely to die or survive with brain damage.

Neuronal Biomarkers in Predicting Neurodevelopmental Outcome in Term Babies with Perinatal Asphyxia.

OBJECTIVE: To assess whether serum levels of neuronal biomarkers (S100 calcium-binding protein B and Neuron specific enolase) correlate with the neurodevelopmental outcome of term neonates at 18 mo who had hypoxic ischemic encephalopathy and underwent therapeutic hypothermia. METHODS: This randomized controlled trial was conducted in a tertiary care teaching hospital, south India. There were 162 term infants with moderate to severe hypoxic ischemic encephalopathy who were randomized into 2 groups (Group A and B). Neonates in Group A and B received normothermia and therapeutic hypothermia respectively. Serum levels of neuronal biomarkers were estimated at 0, 24 (±1) and 72 (±1) h after birth using sandwich ELISA in both groups. All neonates were carefully monitored till discharge. Infants who survived the neonatal period were followed up in the high risk clinic for 18 mo and neurodevelopmental assessment was done using Developmental Assessment Scale for Indian Infants (DASII). Neurodevelopmental outcomes between the two groups were compared using Chi square test and neuronal biomarker levels between the groups were compared using Mann Whitney test. RESULTS: The baseline maternal and neonatal characteristics in both groups were comparable. There was statistically insignificant lesser mortality in therapeutic hypothermia group compared to normothermia group with Risk Ratio (RR): 0.82 (28.2% vs. 34.5%, 95% CI: 0.52-1.29, p = 0.38). Among the survivors, children in therapeutic hypothermia group had better motor and mental scores compared to those in normothermia group at 18 mo. There was no significant correlation between S100B and Neuron specific enolase levels and neurodevelopmental outcome. CONCLUSIONS: Serum levels of neuronal biomarkers (S100B and Neuron specific enolase) do not correlate with the long term neurodevelopmental outcome among these infants.

Oxidative Stress, Antioxidant Status and Neurodevelopmental Outcome in Neonates Born to Pre-eclamptic Mothers.

OBJECTIVES: To measure the oxidative stress and antioxidant status in preeclamptic mother-newborn dyads and correlate them with neurodevelopmental outcome at one year of corrected age. METHODS: This cohort study conducted in a tertiary care teaching hospital, south India included 71 preeclamptic and 72 normal mother-newborn dyads. Biochemical parameters including total antioxidant status (TAS), protein carbonyls and malondialdehyde levels (MDA) were measured in both maternal and cord blood. Infants in both the groups were followed up to one year of corrected age and neurodevelopmental assessment was done using Developmental Assessment Scale for Indian Infants (DASII). Correlation and multivariate regression analysis was done to evaluate the oxidative stress markers in relation to neurodevelopmental outcome. RESULTS: All oxidative stress markers were higher in maternal and cord blood of pre-ecclampsia group compared to the normal group. Maternal Total antioxidant status (M-TAS) was lower in pre-eclampsia group than normal group. More neonates in the pre-ecclampsia group were preterm and intrauterine growth restriction (IUGR) and had higher incidence of morbidities like respiratory distress syndrome (RDS) and early onset sepsis (EOS). Infants in the preeclampsia group had lower motor age, motor score and motor developmental quotient (MoDQ). On multivariate logistic regression analyses, lower M-TAS levels were strongly associated with poor neuro-motor outcomes at 1 y of corrected age. Maternal TAS with a cut-off value of 0.965 mmol/L had a sensitivity of 77.8% and specificity of 55.3% in predicting MoDQ <70 at one year corrected age in infants born to preeclamptic mothers. CONCLUSIONS: Oxidative stress is increased in preeclamptic mother-newborn dyads. Low maternal TAS levels are associated with poor neuro-motor outcomes. Maternal TAS in preeclampsia is useful in predicting poor motor development at one year corrected age.

Maternal and Cord Blood Plasma sEng and TGF-ß1 in Patients with Hypertensive Disorders of Pregnancy: A Pilot Study in a South Indian Population.

INTRODUCTION: Hypertensive Disorders of Pregnancy (HDP) are one of the most widespread complications of pregnancy that affects both mother and foetus. It has been observed that in Preeclampsia, the release of soluble angiogenic factors from the ischemic placenta into maternal plasma plays a crucial role in the pathogenesis. AIM: To assess the plasma Soluble Endoglin (sEng) and Transforming Growth Factor (TGF-ß1) levels in various types of HDP and to correlate the levels of these markers with the pregnancy outcome. MATERIALS AND METHODS: A total of 128 pregnant women were recruited and the study was carried out for a period of three years. Cord blood and maternal blood plasma levels of sEng and TGF-ß1 were analysed by ELISA kits in Control Pregnant Women (CPW), Gestational Hypertension (GH), Early Onset Preeclampsia (EOPE), Late Onset Preeclampsia (LOPE), and Eclampsia (E) during third trimester. The Gestational Age (GA) at the time of delivery and Birth Weight (BW) of the baby also were also evaluated. RESULTS: The circulating levels of maternal and cord blood sEng were significantly higher in EOPE and E compared to CPW and GH. However, the maternal and cord blood levels of TGF-ß1 were significantly lower in LOPE and E when compared to CPW and GH. The GA and BW of the baby were found to be significantly lower in EOPE and E compared to CPW, GH and LOPE. Also, a negative correlation was observed between sEng levels with pregnancy outcome; GA and BW. And also, a positive correlation was found between TGF-ß1 and pregnancy outcome. CONCLUSION: A generalised angiogenic imbalance and poor birth outcomes were observed in HDP. There is a spectrum of biochemical derangements related to angiogenesis in GH, EOPE, LOPE and E.

Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on 'black bone disease' in Italy.

Alkaptonuria (AKU) is an autosomal recessive disorder caused by mutations in homogentisate-1,2-dioxygenase (HGD) gene leading to the deficiency of HGD enzyme activity. The DevelopAKUre project is underway to test nitisinone as a specific treatment to counteract this derangement of the phenylalanine-tyrosine catabolic pathway. We analysed DNA of 40 AKU patients enrolled for SONIA1, the first study in DevelopAKUre, and of 59 other AKU patients sent to our laboratory for molecular diagnostics. We identified 12 novel DNA variants: one was identified in patients from Brazil (c.557T>A), Slovakia (c.500C>T) and France (c.440T>C), three in patients from India (c.469+6T>C, c.650-85A>G, c.158G>A), and six in patients from Italy (c.742A>G, c.614G>A, c.1057A>C, c.752G>A, c.119A>C, c.926G>T). Thus, the total number of potential AKU-causing variants found in 380 patients reported in the HGD mutation database is now 129. Using mCSM and DUET, computational approaches based on the protein 3D structure, the novel missense variants are predicted to affect the activity of the enzyme by three mechanisms: decrease of stability of individual protomers, disruption of protomer-protomer interactions or modification of residues in the region of the active site. We also present an overview of AKU in Italy, where so far about 60 AKU cases are known and DNA analysis has been reported for 34 of them. In this rather small group, 26 different HGD variants affecting function were described, indicating rather high heterogeneity. Twelve of these variants seem to be specific for Italy.

Therapeutic hypothermia using gel packs for term neonates with hypoxic ischaemic encephalopathy in resource-limited settings: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of therapeutic hypothermia (TH) using gel packs in reducing mortality and morbidity in term neonates with HIE and study the associated problems with TH. METHODS: Hypoxic ischaemic encephalopathy babies were randomized into TH and control group. Babies in TH group were cooled for first 72 h of birth using cloth covered cooling gel packs to maintain target rectal temperature of 33-34°C. Infants were followed up to 6 months and were assessed using Baroda Developmental Screening Test. RESULTS: There were no significant differences in baseline parameters. TH group showed significant reduction in the combined rate of death or developmental delay at 6 months of age by 21% (8.1% in the TH group vs. 29% in the control, RR 0.28, 95% CI: 0.11-0.70; p = 0.003). CONCLUSIONS: TH using gel packs reduces the risk of death or developmental delay at 6 months of age in infants with HIE.