Outcomes of Very Preterm Neonates Born by Assisted Reproductive Techniques (ART): A Propensity Score Matched Retrospective Cohort Study

Objective: To compare outcomes of preterm neonates born through assisted reproduction techniques (ART) and non-ART conception. Methods: This retrospective cohort study included very preterm neonates (26 weeks to 31 weeks) admitted to our neonatal unit over a six year period from 2014 to 2019. The primary outcome was composite adverse outcome of mortality or any of the major morbidities i.e., intraventricular hemorrhage (IVH) grade ?3, periventricular leukomalacia (PVL) grade ?2, bronchopulmonary dysplasia (BPD) at 36 weeks, and retinopathy of prematurity (ROP) requiring treatment. Results: Total of 759 neonates (253 in ART group, 506 in non-ART group) were included after propensity score matching for gestational age, sex, and small for gestational age (SGA). Neonates in ART group had similar rates of composite adverse outcome [aOR (95% CI) 0.86 (0.55 – 1.36)], mortality [0.93, (0.53- 1.64)] BPD [1.18, (0.37 – 3.76)]; ROP requiring treatment [ 0.49 (0.14-1.71], and other morbidities. Conclusion: Very preterm neonates born through ART were not at increased risk of adverse neonatal outcomes.

Short-term Outcome and Predictors of Survival Among Neonates With Moderate or Severe Hypoxic Ischemic Encephalopathy: Data From the Indian Neonatal Collaborative

Background: Among term and late preterm infants, hypoxic ischemic encephalopathy (HIE) is an important cause of mortality, and neurologic morbidity among survivors. Objective: The primary objective was to study the incidence of survival to discharge among late preterm and term infants with moderate or severe HIE. Secondary objectives were to explore variation in the management of HIE across participating sites and to identify the predictors of survival. Setting: Indian Neonatal Collaborative (INNC), a network of 28 neonatal units in India. Study design: Retrospective cohort. Participants: Late preterm (34-36 weeks) and term (37-42 weeks) infants with moderate to severe HIE from 2018-2019. Outcome: The primary outcome was survival to discharge (including discharged home and transfer to other hospital). A multivariate logistic regression model was constructed to identify the predictors of survival. Results: Of 352 infants with moderate or severe HIE, 59% received therapeutic hypothermia. Survival to discharge among infants with moderate or severe HIE was 82%. Severe HIE (aOR 0.04; 95% CI 0.02-0.10), persistent pulmonary hypertension (PPHN) (aOR 0.22; 95% CI 0.08-0.61) and requirement of epinephrine during resuscitation (aOR 0.21; 95% CI 0.05-0.84) were independently associated with decreased odds of survival to discharge. Conclusion: Survival to discharge among infants with moderate or severe HIE was 82%. Severe HIE, requirement of epinephrine during resuscitation and PPHN decreased the odds

Quality Improvement Collaborative for Preterm Infants in Healthcare Facilities

Across all healthcare settings, it is important not only to provide safe and effective healthcare, but also to ensure that it is timely, patient-centered, efficient and equitable. There is a wide variability in neonatal and perinatal outcomes in India and other developing countries,with certain units demonstrating clinical outcomes that match the developed world, while others showing higher than expectedmortality and morbidity. Collaborative quality improvement initiatives offer a pragmatic way to improve performance of healthcaredelivery within and between neonatal units. Variations in application of evidence-based healthcare process and dependent healthoutcomes can be identified and targeted for improvement in quality improvement cycles. We herein describe the concept ofCollaborative quality improvement, and the success stories of the best-known Collaborative quality improvement initiatives across theworld. We also highlight the process and progress of creating Collaborative quality improvement in our country.

Phase Changing Material for Therapeutic Hypothermia in Neonates with Hypoxic Ischemic Encephalopathy – A Multi-centric Study

Objective: To assess the feasibility and safety of coolingasphyxiated neonates using phase changing material baseddevice across different neonatal intensive care units in India.Design: Multi-centric uncontrolled clinical trial.Setting: 11 level 3 neonatal units in India from November 2014 toDecember 2015.Participants: 103 newborn infants with perinatal asphyxia,satisfying pre-defined criteria for therapeutic hypothermia.Intervention: Therapeutic hypothermia was provided usingphase changing material based device to a target temperature of33.5±0.5oC, with a standard protocol. Core body temperature wasmonitored continuously using a rectal probe during the coolingand rewarming phase and for 12 hours after the rewarming wascomplete.Outcome measures: Feasibility measure - Time taken to reachtarget temperature, fluctuation of the core body temperatureduring the cooling phase and proportion of temperaturerecordings outside the target range. Safety measure - adverseevents during coolingResults: The median (IQR) of time taken to reach targettemperature was 90 (45, 120) minutes. The mean (SD) deviationof temperature during cooling phase was 33.5 (0.39) ºC.Temperature readings were outside the target range in 10.8%(5.1% of the readings were <33oC and 5.7% were >34oC). Mean(SD) of rate of rewarming was 0.28 (0.13)oC per hour. Thecommon adverse events were shock/ hypotension (18%),coagulopathy (21.4%), sepsis/probable sepsis (20.4%) andthrombocytopenia (10.7%). Cooling was discontinued before 72hours in 18 (17.5%) babies due to reasons such as hemodynamicinstability/refractory shock, persistent pulmonary hypertension orbleeding. 7 (6.8%) babies died during hospitalization.Conclusion: Using phase changing material based coolingdevice and a standard protocol, it was feasible and safe to providetherapeutic hypothermia to asphyxiated neonates across differentneonatal units in India. Maintenance of target temperature wascomparable to standard servo-controlled equipment.

Comparison of Sucking Pattern in Premature Infants with Different Feeding Methods.

Objective: To compare the sucking pattern of preterm infants on different feeding methods. Methods: The sucking behavior on a gloved finger was evaluated for infants receiving breastfeeding, spoon-feeding and tube-feeding. Results: The mean (SD) numbers of sucks in spoon-fed infants [49 (20) vs. 35 (23); P=0.04] were significantly higher, and the grade of suck was significantly better compared to the tubefed group. The mean (SD) number of sucks was significantly higher [83 (30) vs. 49 (20), P<0.001] in breastfed infants compared to spoon-fed infants; all infants on breast feeds had grade 2 suction. Conclusion: The sucking behavior varies between tube-fed, spoon-fed, and breastfed preterm infant.

Continuous Positive Airway Pressure in Preterm Neonates: An Update of Current Evidence and Implications for Developing Countries.

Context: Continuous Positive Airway Pressure (CPAP) is a cost-effective and minimal invasive respiratory support for the newborn. Objective: To review the evidence related to various aspects of CPAP usage and its applicability for developing countries. Evidence Acquisition: We conducted a literature search on PubMed, CENTRAL, and Cochrane Database of Systematic Reviews using the terms ‘CPAP’ OR ‘continuous positive airway pressure’ OR, non-invasive ventilation’ AND ‘newborn’ OR ‘neonate’ OR ‘infant’. We also searched the reference lists from the above articles and of review articles. Extracted manuscripts and reviews were analyzed and results related to various aspects of CPAP usage were summarized in narrative form. Results: Early use of CPAP with early rescue surfactant (InSurE) is the ideal approach for management of respiratory distress syndrome in preterm and extremely preterm infants. Delivery room CPAP is feasible and reduces the need for surfactant and mechanical ventilation by nearly 50%. Prophylactic surfactant for extreme preterms should be discouraged. Heated humidified high flow nasal cannula is best utilized for post-extubation respiratory support. The search for ideal interface still continues and binasal prongs or nasal masks are the good contenders. Evidence on the ideal CPAP delivery is still inconclusive. Conclusions: CPAP, if used early and judiciously, is an effective intervention and need immediate scaling-up in resource-limited settings. Future research should focus on the ideal interface and the CPAP delivery methods.

Bilateral Pleural Effusion Complicating Umbilical Venous Catheterization.

Background: Umbilical venous lines are sometimes complicated with pleural and or pericardial effusion, often due to line migration. Case Characteristics: Bilateral chylous pleural effusion without pericardial effusion in a 28 weeks, extremely low birth infant who was on total parenteral nutrition. Observations/Investigations: Investigations including chest x ray and 2D echocardiogram showed bilateral chylous pleural effusions but appropriate tip position of the umbilical venous line. Outcome: Removal of the umbilical venous line and cessation of total parenteral nutrition resulted in complete resolution of the pleural effusion. Message: In any newborn with central venous catheter in situ, acute deteriorations specially, those related to pleural and pericardial effusions should alert the clinicians to remove the catheter and should not be misguided by apparently appearing normal correct catheter position by x-ray or 2D echocardiogram.

Survival and Morbidity Among Two Cohorts of Extremely Low Birth Weight Neonates from a Tertiary Hospital in Northern India.

This study was conducted to compare the survival and morbidity of extremely low birth weight neonates born during two different time periods (2009-10 and 2001-02) at a Level III referral neonatal unit in Northern India. All consecutive intramural extremely low birth weight neonates (<1000g), irrespective of gestation, and admitted to Intensive Care were enrolled. 149 and 123 neonates were enrolled during 2009-10 and 2001-02, respectively. The baseline characteristics were comparable except for mean birth weight, which was lower during 2009-10 (843±108g vs 885±126g, P=0.003). Surfactant therapy (54% vs 18%, P<0.001), non-invasive ventilation (28% vs 6%, P<0.001), high frequency ventilation (24% vs 4%, P=0.001), IVH (52% vs 25%, P<0.001) and PDA (34% vs 18%, P=0.004) were significantly more during 2009-10. Culture positive sepsis (33% vs 51%, P=0.003) and ROP rates (7% vs 23%, P=0.042) were significantly higher during 2001-02. Overall survival was similar; however, neonates between 28-30 weeks gestation had better survival (63%) during 2009-10 compared to 2001-02 (38%), P=0.009. Survival in neonates 28-30 weeks improved during this period while overall survival remained the same.

Gestational Age-specific Centile Charts for Anthropometry at Birth for South Indian Infants.

Objective: To construct centile charts for birth weight, length and head circumference for infants born from 24 to 42 weeks of gestation and to compare with the other national and international growth charts. Study design: Observational descriptive study. Subjects: All consecutively live born singleton infants from 24 to 42 weeks of gestation. Methods: Data were retrieved for the birth weight, length and head circumference of infants born from July 1999 to October 2009. Smoothened percentile curves were created separately for the male and female infants by Lambda Mu Sigma (LMS) method. The new curves were compared with the other Indian and international growth charts. Results: Raw and smoothened curves for weight, length and head circumference centiles at birth were created from 31,391 (males: 16,054 and females: 15,337), 28,812, (males: 14,730 and females: 14,082), and 28,790 (males: 14,724 and females: 14,066) infants, respectively. Females infants were lighter than the male infants, especially from 35 weeks onwards. On comparing the study curves with the other Indian growth curves, for infants less than 35 weeks, the mean birth weight for the study infants were similar or lower and for infants greater than 35 weeks, they were higher. On comparison of our weight centiles with the international data, across all gestations and across all centiles, our birth weights are lower. Conclusion: The updated centile charts in this study may be used as reference charts for the birth weight, length and head circumference for the local population. Using earlier growth charts or the Western charts would misclassify the infants at birth into SGA or LGA.

Early Neonatal Morbidities in Late Preterm Infants.

Objectives: To compare early neonatal morbidity (within first 7 days of life) in late preterm infants with term infants. Study design: Prospective cohort study. Subjects: All live inborn late preterm infants (34 0/7 to 36 6/7 weeks) and term infants (37 0/7 to 41 6/7 weeks). Outcome: Any of the predefined medical conditions listed in the study, resulting in post- delivery inpatient hospital observation, admission, or readmission in first 7 days of life. Results: 363 late preterm infants and 2707 term infants were included in study. Two hundred fifty seven (70.8 %) of late preterm and 788 (29.1%) of term infants had at least one of the predefined neonatal conditions. Late preterm infants were at significantly higher risk for overall morbidity due to any cause (P<0.001; adjusted Odds Ratio (OR): 5.5; 95% CI: 4.2-7.1), respiratory morbidity (P<0.001; adjusted OR: 7.5; 95% CI: 4.2-12.3), any ventilation (non invasive or invasive) (P=0.001; adjusted OR: 4.2; 95% CI: 2-8.9), jaundice (P<0.001; adjusted OR: 3.4; 95% CI: 2.7- 4.4), hypoglycemia (P<0.001; adjusted OR: 4.5; 95% CI: 2.6-7.7), and probable sepsis (P<0.001; adjusted OR: 3.2; 95% CI: 1.6-6.5). The incidence of morbidities increased from 23% at 40 weeks to 30%, 39.7%, 67.5%, 89% and 87.9% at 38, 37, 36, 35 and 34 weeks, respectively (P<0.001). Conclusion: Compared with term infants, late preterm infants are at high risk for respiratory morbidity, need of ventilation (non invasive or invasive), jaundice, hypoglycemia, sepsis, and probable sepsis. All gestations except 39 weeks were at significantly higher risk for morbidity with 40 weeks as reference term.

Restriction of Cephalosporins and Control of Extended Spectrum β-Lactamase Producing Gram Negative Bacteria in a Neonatal Intensive Care Unit.

This interventional study with historical controls was conducted to study the effect of cephalosporin restriction on the incidence of extended spectrum betalactamase (ESBL) gram negative infections in neonates admitted to intensive care unit. All gram negative isolates from the blood were evaluated for beta lactamase production. The incidence of ESBL production was compared before (year 2007) and after cephalosporin restriction (year 2008). Thirty two neonates (3% of NICU admissions) in the year 2007 and fifty six (5.2%) in the year 2008, had gram negative septicemia. The incidence of ESBL gram negatives decreased by 22% (47% to 25%, P=0.03). Restriction of all class of cephalosporins significantly decreased the incidence of ESBL gram negative infections.

Congenital chylothorax - Successful management with chemical pleurodesis.

Congenital Chylothorax is a rare entity which is characterized by abnormal accumulation of chyle in pleural cavity. Chylothorax presenting as non-immune hydrops is even rarer. We report a case of congenital bilateral chylothorax presenting as non immune hydrops and managed successfully with chemical pleurodesis. A term male baby presented at birth with bilateral pleural effusions and subcutaneous edema. It was initially managed with ventilation and intercostals drainage (ICD). After the initiation of feeds, re-accumulation of pleural fluid led to the diagnosis of congenital chylothorax. Management with ICD and octreotide was unsuccessful but responded to chemical pleurodesis with 4% povidine iodine done on 3 separate occasions.

Bubble CPAP for Respiratory Distress Syndrome in Preterm Infants.

Objectives: To ascertain the immediate outcome of preterm infants with respiratory distress syndrome (RDS) on Bubble CPAP and identify risk factors associated with its failure. Study design: Prospective analytical study. Subjects: Inborn preterm infants (gestation 28 to 34 weeks) admitted to the NICU with respiratory distress and chest X- ray suggestive of RDS. Intervention: Bubble CPAP with bi-nasal prongs. Primary outcome: CPAP failures-infants requiring ventilation in the first one week. Results: 56 neonates were enrolled in the study. 14 (25%) babies failed CPAP. The predictors of failure were; no or only partial exposure to antenatal steroids, white-out on the chest X-ray, patent ductus arteriosus, sepsis/ pneumonia and Downe's score >7 or FiO2 ≥50% after 15- 20 minutes of CPAP. Other maternal and neonatal variables did not influence the need for ventilation. Rates of mortaility and duration of oxygen requirement was significantly higher in babies who failed CPAP. Only two infants developed pneumothorax. No baby had chronic lung disease. Conclusion: Infants with no or partial exposure to antenatal steroids, white-out chest X-ray, patent ductus arteriosus, sepsis/pneumonia and those with higher FiO2 requirement after initial stabilization on CPAP are at high risk of CPAP failure (needing mechanical ventilation). Bubble CPAP is safe for preterm infants with RDS.

Light-emitting Diodes versus Compact Fluorescent Tubes for Phototherapy in Neonatal Jaundice: A Multi-center Randomized Controlled Trial.

Objective: To evaluate whether light-emitting diode (LED) phototherapy is as efficacious as compact fluorescent tube (CFT) phototherapy for the treatment of nonhemolytic jaundice in healthy term and late preterm neonates. Study design: Multi-centre open-label randomized controlled trial. Setting: Four tertiary care neonatal units. Subjects: Healthy term and late preterm neonates with nonhemolytic jaundice. Intervention: Single-surface LED or CFT phototherapy. Primary outcome variable: Duration of phototherapy. Results: A total of 272 neonates were randomized to receive LED (n=142) or CFT (n=130) phototherapy. The baseline demographic and biochemical variables were similar in the two groups. The median duration of phototherapy (IQR) in the two groups was comparable (26 (22-36) h vs. 25(22-36) h; P=0.44). At any time point, a similar proportion of neonates were under phototherapy in the two groups (log-rank test, P=0.38). The rate of fall of serum total bilirubin (STB) during phototherapy and the incidence of ‘failure of phototherapy’ were also not different. An equal proportion of neonates had a rebound increase in STB needing restarting of phototherapy. Side effects were rare, comparable in the two groups and included hypothermia, hyperthermia, rash, skin darkening and dehydration. Conclusions: LED and CFT phototherapy units were equally efficacious in the management of non-hemolytic hyperbilirubinemia in healthy term and late-preterm neonates.

Effects of cessation of a policy of neonatal fluconazole prophylaxis on fungal resurgence.

Fluconazole has been used as prophylaxis against systemic fungal infections in preterm neonates. We conducted a study to determine whether cessation of a policy of prophylactic fluconazole results in a resurgence of fungal infections in a unit. Neonates born in the 3 epoches: A 36-month pre-Fluconazole prophylaxis epoch (Group 1), a 21-month Fluconazole prophylaxis epoch (Group 2) and a 39-month post Fluconazole prophylaxis epoch (Group 3) were compared for incidence and onset of fungal sepsis and resistance patterns. There was a decline in the incidence of fungal sepsis from Group 1 to Group 2, and it remained stable from Group 2 to Group 3. There was no significant difference in resistance to Fluconazole and to any of the azoles in Groups 1, 2 and 3 respectively.