Immunoglobulin Profile and Lymphocyte Subsets in Preterm Neonates

Objective: We documented the immunological profile of neonates and mothers, and lymphocyte subsets at birth. Methods: Consecutively born preterm neonates (26 to 31 weeks gestation) at our level III neonatal unit, fulfilling the inclusion criteria were enrolled. Immunoglobulin levels were assessed in maternal blood and in cord blood along with T cell subsets. Results: A total of 115 neonates were enrolled. The mean cord levels for IgG, IgM and IgA, respectively were 5.34, 0.10 and 0.04 g/L and of B, T, NK and NK-T cells were 14%, 71%, 10% and 1%, respectively of total lymphocyte population. Cord IgG and IgA levels showed a significantly rising trend with increasing gestation (P=0.005 and 0.02, respectively) but not IgM and T cell subsets. Maternal immunoglobulins were similar in all gestations. Conclusion: The cord IgG and IgA increased with increasing gestation but not IgM in neonates.

Clinical characteristics & outcome of SARS-CoV-2 infected neonates presenting to paediatric emergency

Background & objectives: Data on neonatal COVID-19 are limited to the immediate postnatal period, with a primary focus on vertical transmission in inborn infants. This study was aimed to assess the characteristics and outcome of COVID-19 in outborn neonates. Methods: All neonates admitted to the paediatric emergency from August 1 to December 31, 2020, were included in the study. SARS-CoV-2 reverse transcription- (RT)-PCR test was done on oro/nasopharyngeal specimens obtained at admission. The clinical characteristics and outcomes of SARS-CoV-2 positive and negative neonates were compared and the diagnostic accuracy of a selective testing policy was assessed. Results: A total of 1225 neonates were admitted during the study period, of whom SARS-CoV-2 RT-PCR was performed in 969. The RT-PCR test was positive in 17 (1.8%). Mean (standard deviation) gestation and birth weight of SARS-CoV-2-infected neonates were 35.5 (3.2) wk and 2274 (695) g, respectively. Most neonates (11/17) with confirmed COVID-19 reported in the first two weeks of life. Respiratory distress (14/17) was the predominant manifestation. Five (5/17, 29.4%) SARS-CoV-2 infected neonates died. Neonates with COVID-19 were at a higher risk for all-cause mortality [odds ratio (OR): 3.1; 95% confidence interval (CI): 1.1-8.9, P=0.03]; however, mortality did not differ after adjusting for lethal malformation (OR: 2.4; 95% CI: 0.7-8.7). Sensitivity, specificity, accuracy, positive and negative likelihood ratios (95% CI) of selective testing policy for SARS-CoV-2 infection at admission was 52.9 (28.5-76.1), 83.3 (80.7-85.6), 82.8 (80.3-85.1), 3.17 (1.98-5.07), and 0.56 (0.34-0.93) per cent, respectively. Interpretation & conclusions: SARS-CoV-2 positivity rate among the outborn neonates reporting to the paediatric emergency and tested for COVID-19 was observed to be low. The selective testing policy had poor diagnostic accuracy in distinguishing COVID-19 from non-COVID illness.

Screening for Language Delay between 6 Months and 3 Years of Corrected Age in Very Low Birth Weight Children

Objective: To screen for language delay in very low birth weight (VLBW) children between6 months to 3 years using Language Evaluation Scale Trivandrum, 0-3 years. Methods:VLBW inborn neonates at a corrected age of 6 months to 3 years visiting follow-up clinicwere enrolled. Children with hearing loss were excluded. Prevalence and predictors oflanguage delay were ascertained. Results: Of 200 enrolled subjects, out of the 1400VLBW discharged, 64 (32%) had language delay. On multivariate analysis, late onsetsepsis, patent ductus arteriosus and poor socioeconomic status were significant predictorsof language delay. Abnormal neurological examination and suspect development were alsoassociated with language delay. Conclusions: In VLBW children, the frequency oflanguage delay is quite high. These children should be screened for language delay.

Bronchopulmonary Dysplasia in Preterm Neonates in a Level III Neonatal Unit in India

Objective: To find out the incidence and associations ofbronchopulmonary dysplasia (BPD) in preterm neonates.Design: Descriptive cohort.Methods: All consecutively born neonates <33 weeks gestationrequiring oxygen or respiratory support during first 3 days of lifewere enrolled from a level III neonatal unit in Chandigarh, India.Those with malformations were excluded. Placenta wasexamined for histological chorioamnionitis in preterm rupture ofmembranes and/or preterm spontaneous onset of labour. SerumMalondialdehyde (MDA) and Superoxide dismutase (SOD) andCatalase levels were estimated on day 3 of life. All recruitedneonates were followed up till discharge or death.Results: Out of 250 neonates enrolled, 170 (68%) survived tillday 28 and BPD developed in 19 (11.2%) infants. The meangestation and birth weight were significantly lower in infants whodeveloped BPD. Chorioamnionitis (clinical 5.3% vs 1.9%,P=0.375; and histological 37.5% vs 16.7%, P<0.001), patentductus arteriosus (PDA) (52.6% vs 8.9%, P<0.001), median (IQR)sepsis episodes [2 (2,3) vs 1 (1,2), P<0.001], invasive ventilation(84.2% vs 11.3%, P<0.001), and duration of ventilation [56 (4) d vs4 (5) d, P=0.001] were significantly higher in infants with BPD.Serum MDA, SOD and Catalase levels were comparable betweenthe two groups.Conclusion: Chorioamnionitis, PDA and sepsis were significantlyassociated with BPD.

Neurodevelopmental Outcome of Extremely Low Birth Weight Children at Corrected Age of Two Years.

Objective: To assess the neurodevelopmental, cognitive and behavioral function of extremely low birth weight babies (ELBW) till corrected age of two years. Methods: 79 ELBW babies were enrolled and followed at 1 year (n=50), 18 months (n=47) and 2 years (n=36). Adverse composite outcome was defined as death or moderate-to- severe neurodevelopmental impairment (defined as either cerebral palsy or DQ score <70 or deafness or blindness). Results: At 1 year, 24% were neurologically abnormal. At 18 months, average score (>85) was seen in 25 (54%) children in motor and 8 (17%) in mental development. Abnormal behavioral score (³12) was seen in 89% children. Adverse composite outcome was present in 28 (35.4 %) babies. Conclusion: ELBW neonates are at a high risk of neurodevelopmental and behavioral impairment.

Oromotor Stimulation for Transition from Gavage to Full Oral Feeding in Preterm Neonates: A Randomized controlled trial.

Objective: To assess the effect of additional oromotor stimulation along with routine care on transition from gavage to full oral feeding in preterm neonates. Method: 51 neonates (28-34 weeks) randomized to receive either oromotor stimulation along with routine care (n=25, intervention), or routine care alone (n=26, control) (which included Kangaroo mother care and non-nutritive sucking). Results: Median (IQR) days to reach partial and full spoon feed were significantly lesser [5(3-9.5) vs 10(5-15) P=0.006; and 7(5-14.5) vs 12.5(7-21); P=0.03] in intervention than in control group, respectively. A significantly higher number (56%) in intervention group as compared to control group (31%) achieved partial direct breast feeding at discharge (P=0.01). Conclusion: Oromotor stimulation along with routine care reduces the duration of gavage feeding in preterm neonates.

Longitudinal Growth and Post-discharge Mortality and Morbidity Among Extremely Low Birth Weight Neonates.

Objectives: To study post-discharge growth, mortality and morbidity of extremely low birth weight neonates at corrected age of 2 years. Methods: Weight, length and head circumference were compared on WHO growth charts at corrected ages 3 (n=54), 6, 9, 12 (n=51) and 24 months (n=37); rates of underweight, stunting, microcephaly and wasting were calculated. Results: The mean Z-score for weight, length, head circumference and weightfor- length significantly improved from 3 to 24 months (P<0.001); a significant proportion remained malnourished at 2 years. Nine infants (11%) died and 35 (44%) required readmission during first year of age. Conclusion: Extremely low birth weight neonates remain significantly growth retarded at corrected age of 2 years.

Predictors of Mortality in Neonates with Meconium Aspiration Syndrome.

Objective: To identify risk factors for mortality in neonates with meconium aspiration syndrome. Methods: All neonates (2004-2010) with meconium aspiration syndrome, irrespective of gestation were included. Risk factors were compared between those who died and survived. Results: Out of 172 included neonates, 44 (26%) died. Mean (SD) gestation and birth weight were 37.9 (2.3) weeks and 2545 (646g), respectively. Myocardial dysfunction [aOR 28.4; 95% CI (8.0-101); P<0.001] and higher initial oxygen requirement [aOR 1.04; 95% CI (1.02-1.07); P<0.001] increased odds of dying while a higher birth weight [aOR 0.998; 95% CI (0.997-1.00); P=0.005] reduced the odds of dying. Conclusions: Meconium aspiration syndrome is associated with significant mortality. Myocardial dysfunction, birth weight, and initial oxygen requirement are independent predictors of mortality.

Human Milk Banking Guidelines.

Justification: WHO and UNICEF state that the use of human milk from other sources should be the first alternative when it is not possible for the mother to breastfeed. Human milk banks should be made available in appropriate situations. The IYCF Chapter is actively concerned about the compelling use of formula feeds in the infants because of the non availability of human breast milk banks. Process: A National Consultative Meet for framing guidelines was summoned by the IYCF Chapter and the Ministry of Health and Family Welfare, Government of India on 30th June, 2013, with representations from various stakeholders. The guidelines were drafted after an extensive literature review and discussions. Though these guidelines are based on the experiences and guidelines from other countries, changes have been made to suit the Indian setup, culture and needs, without compromising scientific evidence. Objectives: To ensure quality of donated breast milk as a safe end product. Recommendations: Human Milk Banking Association should be constituted, and human milk banks should be established across the country. National coordination mechanism should be developed with a secretariat and technical support to follow-up on action in States. Budgetary provisions should be made available for the activities.

Predictors of Mortality and Major Morbidities in Extremely Low Birth Weight Neonates.

Objectives: To determine predictors of mortality and morbidity in extremely low birth weight neonates (ELBW) from a developing country Study design: Prospective observational study. Setting: Level III neonatal unit in Northern India. Subjects: Neonates <1000g born and admitted to intensive care during study period were enrolled. They were analyzed based on survival and development of major morbidity. Multivariable logistic regression model was used to determine independent risk factors. Outcome: Mortality and major morbidity (one or more of the following: Bronchopulmonary dysplasia (BPD), Retinopathy of Prematurity (ROP) requiring laser, grade III or IV intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL) and necrotizing enterocolitis (NEC) stage III) during hospital stay. Results: Of 255 ELBW neonates born, 149 received optimal care, of which 78 (52%) survived and 57 (39%) developed morbidities. Mean birth weight and gestational age were 29.1±2.6 weeks and 843±108g. Major causes of mortality were sepsis (46%), birth asphyxia (20%) and pulmonary hemorrhage (19%). Birth weight ≤800g [OR (95% CI)-3.51 (1.39-8.89), P=0.008], mechanical ventilation [4.10 (1.64-10.28), P=0.003] and hypotensive shock [10.75 (4.00-28.89), P<0.001] predicted mortality while birth weight ≤800g [3.75 (1.47-9.50), P=0.006], lack of antenatal steroids [2.62 (1.00-6.69), P=0.048), asphyxia [4.11 (1.45-11.69), P=0.008], ventilation [4.38 (1.29-14.79), P=0.017] and duration of oxygen therapy [0.004 (1.001-1.006), P=0.002] were the predictors of major morbidities. Conclusions: Low birth weight, mechanical ventilation and hypotensive shock predicted mortality in ELBW neonates while low birth weight, lack of antenatal steroids, birth asphyxia, ventilation and duration of oxygen therapy were predictors for major morbidity.

Neurodevelopmental and behavioral outcome of very low birth weight babies at corrected age of 2 years.

Objective Neurodevelopmental and behavioral assessment of very low birth weight babies (VLBW) at corrected age (CA) of 2 years. Methods 127, 110, 99 and 101 babies ≤34 weeks and ≤1500 g were followed at CA of 3, 6, 9, 12 months respectively for developmental and neurological assessment. DASII (Developmental assessment scale for Indian infants) was used at CA of 18 months and preschool behavioural checklist (PBCL) at CA 2 years. Results Of 101 VLBW babies available for follow up at CA 1 year, 3 (3%) babies had Cerebral Palsy (CP) and 3% (n=3) had suspect abnormality (mild hypotonia), 11% (n= 11) had gross motor and 8% (n=8) had language abnormality. Their mean mental (MeDQ) and motor (MoDQ) quotients were 80.4±10.7 and 77.2±13.3 and a score of<70 was found in 17% (MeDQ) and 25.7% (MoDQ) VLBW babies. High PBCL score (mean 16.8± 5.4) was seen in 84%VLBW babies. On subgroup analysis, 2 babies (5%) in subgroup1 ( n=54, ≤1200 g,) and 1 (1.6%) in subgroup 2 (n=78, 1201–1500 g) had CP. Twelve (29%) in subgroup 1 had significant language delay (p=0.004) as compared to 4 (15%) in subgroup 2 at 1 year. BSID and PBCL scores were comparable. Amongst ELBW babies (<1000 g), 6.6% (n=1) had CP, 25% (n=3) and 42% (n=5) had low MeDQ and MoDQ respectively and all of them had high PBCL score. AGA and SGA had similar outcome. Conclusion VLBW babies need close and longer follow up due to high risk of neurodevelopmental and behavioral abnormality.

Effect of human milk fortification in appropriate for gestation and small for gestation preterm babies: a randomized controlled trial.

OBJECTIVE: To study the effects of human milk fortification on short term growth and biochemical parameters in preterm very low birth weight (VLBW) appropriate for gestation (AGA) and small for gestation (SGA) babies. DESIGN: Prospective, randomized controlled trial. SETTING: Level III neonatal unit. SUBJECTS: Preterm infants weighing < or = 1500 grams and < or = 34 weeks of gestation born between March 2001 to June 2002. METHODS: Babies (n =166) were randomized in two groups either to get fortified human milk or exclusive human milk along with mineral and vitamin supplementation when feed volume reached 150 mL/Kg/day. Fortification was done with a powdered fortifier added in expressed breast milk and continued till the baby reached 2 Kg or full breast feeds. Primary outcome measures were Short-term growth (daily weight, length and head circumference (HC) weekly) till discharge or 2 Kg. RESULTS: Fortification (n = 85, birth weight 1202 g, gestation 30.8 wk) resulted in better growth in preterm VLBW babies as compared to control group (n=81, birth weight 1259 g, gestation 31.3 wk). Weight gain (15.1 and 12.9 g/kg/d, P <0.001), length (1.04 and 0.86 cm/week, P = 0.017) and HC (0.83 and 0.75 cm/week, P<0.001) increased significantly in fortified group. SGA babies showed significant improvements in weight (16 g/Kg/d and 12.9 g/kg/d, P = 0.002) and length (1.09 cm/week and 0.92 cm/week, P = 0.042) in fortified group (n = 38) as compared to control group (n = 29). In AGA subgroup, there was significant increase (P = 0.006) in length (1 cm vs 0.82 cm) in fortified group but no difference in weight (P = 0.12) or HC (P=0.054) in fortified (n=47) vs control (n=52) group. Biochemical parameters were comparable, however feed intolerance was more in control group. CONCLUSION: Preterm VLBW babies showed better growth with human milk fortification. The effect is significant in SGA (weight and length)rather than AGA (only length) babies.

Infantile cortical hyperostosis.

Infantile cortical hyperostosis (Caffey disease) is characterized by radiological evidence of cortical hyperostosis, soft tissue swellings, fever and irritability. We report a case of Caffey disease highlighting its presentation as pyrexia of unknown origin, appearance on radionuclide bone scintigraphy and our unsatisfactory experience of treating it with Ibuprofen, a prostaglandin inhibitor.

Intravenous immunoglobulins in rhesus hemolytic disease.

OBJECTIVE: To evaluate the role of intravenous immunoglobulins in Rh hemolytic disease of newborn. METHODS: The study included all DCT positive Rh isoimmunized babies admitted in the unit from August 2000 to February 2001. Intravenous immunoglobulins in the dose of 500 mg/kg on day 1 and day 2 of life in addition to the standard therapy. Babies who received IVIG were compared with those who did not receive IVIG for the peak bilirubin levels, duration of phototherapy, number of exchange transfusions, discharge PCV and the need for blood transfusions for late anemia till 1 months of age. RESULTS: A total of 34 babies were eligible for the study. 8 babies received IVIG and 26 babies only standard treatment. The mean maximum bilirubin levels were significantly lower in the IVIG group compared to the group who received NO IVIG (16.52 +/- 2.96 Vs 22.72 +/- 8.84, p=0.004). Five babies in the IVIG group (62.5%) and 23 babies in the NO IVIG group required exchange transfusions (88.5%, p=0.014). 12 of the 26 babies in the NO IVIG group required multiple exchange transfusions while none of the babies in IVIG group required more one exchange transfusion (p=0.03). The mean duration of phototherapy was 165 +/- 109 hours in the IVIG group as against 119 +/- 56 hours in the NO IVIG group (p=0.29). Blood transfusion for anemia was more common in the IVIG group (37.5% Vs 11.5% p=0.126) though the packed cell volumes at discharge were similar in both the groups (39.5 +/- 11 Vs 40 +/- 5.1, P=0.92). CONCLUSION: Intravenous immunoglobulins is effective in decreasing the maximum bilirubin levels and the need for repeated exchange transfusions in Rh hemolytic disease of newborn. There is however an increased need for blood transfusions for late anemia in the babies treated with IVIG.