Fluid Supplementation versus No Fluid Supplementation in Late Preterm and Term Neonates with Asymptomatic Polycythemia: A Randomized Controlled Trial.

Objective: To compare supplemental intravenous fluids with no supplementation in asymptomatic polycythemic late preterm and term neonates. Methods: 55 infants with venous haematocrit of 65-75 were randomly allocated to receive either 25 mL/kg IV normal saline over 6-8 hours or routine fluids. They were followed up for 48 hours. Results: There was no significant difference between fluid supplementation and control groups regarding need for partial exchange transfusion [6/27 (22.2%) vs 8/28 (28.6%); P=0.59]. Conclusions: We did not find any evidence of clinical benefit with IV fluid supplementation in late preterm and term neonates with asymptomatic polycythemia (PCV 65-75).

Stress in Fathers of Premature Newborns Admitted in a Neonatal Intensive Care Unit.

Objective: To study stress in fathers of preterm infants admitted in a neonatal intensive care unit. Methods: Questionnaire-based study. Questionnaire included domains on infant’s health, maternal illness, staff behavior, parental role, home affairs and finances. Eligible fathers were repeatedly interviewed on day 7 (n=80), day 17 (n=59) and day 27 (n=28). Raw and standardized stress scores were calculated. Results: Financial burden was the main stressor at all times. Stress related to staff behavior and altered parental role reduced with time. Birthweight and father’s age, occupation and education independently predicted stress. Conclusions: Fathers of preterm infants admitted in hospital are stressed, primarily due to financial burden.

Intestinal Colonization Among Very Low Birth Weight Infants in First Week of Life.

Objective: To study intestinal colonization patterns in very low birth weight infants in the first week of life in a neonatal intensive care unit. Methods: Meconium/stool specimens were obtained on days 1, 3, 5 and 7 from 38 very lowbirth- weight infants in a level III neonatal intensive care unit. Results: On day 1, 45% had sterile guts, and by day 3, all infants were colonized. E. coli, K. pneumoniae and Enterococcus fecalis were predominant organisms. Lactobacilli was found in one isolate and Bifidobacteria was not detected during the study period. There was an association between formula feeding and E. coli colonization. Conclusions: Very low birth weight infants admitted in neonatal intensive care units have abnormal intestinal colonization patterns.

Short Course Versus 7-Day Course of Intravenous Antibiotics for Probable Neonatal Septicemia: A Pilot, Open-label, Randomized Controlled Trial.

Objective: To compare a short course of antibiotics (48 to 96 hours) and a standard course of antibiotics (7 days) for probable neonatal sepsis. Design: Randomized, controlled, open-labeled trial with blocking and stratification according to birth weight. Setting: Tertiary care, referral, teaching hospital in Northern India. Participants: Neonates >30 wks gestation and >1000 g at birth, with probable sepsis (clinical signs of sepsis, raised C-reactive protein) were enrolled. Babies with major malformations, severe birth asphyxia, meningitis, bone or joint or deep-seated infection, those who were already on antibiotics, and those undergoing surgery were excluded. Neonates, who had clinically remitted on antibiotic therapy – by the time a sterile blood culture report was received – were randomized. Intervention: In the intervention arm, antibiotics were stopped after the 48-hour culture was reported sterile. In the control arm, antibiotics were continued to a total of 7 days. Main outcome measure: “Treatment failure” defined as reappearance of signs suggestive of sepsis within 15 days of stopping antibiotics, supported by laboratory evidence and adjudicated by a blinded expert committee. Results: 52 neonates were randomized to receive a short course or 7-day course (n=26 each). Baseline variables were balanced in the 2 groups. There was no significant difference in the treatment failures between the 2 groups (3 babies in the 7-day group vs none in short course group, P=0.23). Conclusion: No difference in the treatment failure rates could be identified between short course and 7-day groups among neonates >30 weeks and >1000 grams with probable sepsis.

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.

Gemfibrozil in Late Preterm and Term Neonates with Moderate Jaundice: A Randomized Controlled Trial.

Objective: To determine, if oral Gemfibrozil is effective in decreasing the duration of phototherapy by at least 24 hours in neonates >34 weeks gestation with nonhemolytic jaundice, as compared to placebo. Design: Double blind placebo controlled randomized controlled trial. Setting: Tertiary care neonatal unit in north India. Subjects: Ninety seven neonates >34 weeks gestation with non-hemolytic jaundice within first 7 days of life requiring phototherapy. Intervention: Two doses of Gemfibrozil (60 mg/kg/dose) or placebo, 12 hours apart. Babies were treated with single surface special blue light phototherapy. Serum total bilirubin (STB) was measured 8 hourly. Phototherapy was stopped if two consecutive STB values were below phototherapy zone. Primary outcome measure: Duration of phototherapy. Results: The median (IQR) duration of phototherapy was 40 (30, 60) hours in Gemfibrozil and 36 (19, 55) hours in the placebo group (P=0.13). The peak STB levels were 16.8 ± 2.7 mg/dL and 16.3 ± 2.3 mg/dL in Gemfibrozil and placebo groups, respectively. No side effect of the drug or placebo was noticed. Conclusion: Two doses of gemfibrozil (60mg/kg/dose) given 12 hours apart were not able to reduce the duration of phototherapy, or peak bilirubin level in babies > 34 weeks gestation with non-hemolytic jaundice in the first week of life. Gemfibrozil was not associated with any side effects.

Score for neonatal acute physiology II predicts mortality and persistent organ dysfunction in neonates with severe septicemia.

Objective: To investigate the relationship between score for neonatal acute physiology II (SNAP II) applied within 12 hours from the onset of severe sepsis, and death and persistent organ dysfunction (OD). Design: Prospective cohort study. Setting: Level III neonatal intensive care unit. Participants: Neonates with severe sepsis. Intervention:SNAP II was applied within the first 12 hours from the onset of severe sepsis. Neonates with major malformations, severe asphyxia and prior blood products were excluded. Major outcome measure: Death at day 14 from enrolment. Results: Forty neonates completed the study. Twenty-five died within 14 days. The median SNAP II was significantly higher in babies who died versus those who survived [median (IQR): 43 (36 – 53.5) vs 18 (16 - 37), P<0.001]. A SNAP II greater than 40 had 88% positive predictive value for death and persistent OD each, and 86.6% and 86% specificity for death and persistent OD, respectively. On day 14 from enrolment, more organs normalized/improved in the subjects with SNAP II of £40. Perfusion related SNAP II parameters were significantly associated with death and organ dysfunction. Conclusions: Severely septicemic neonates with high SNAP II scores (>40) have a higher risk of dying and persistent organ dysfunction. Individual SNAP II parameters do not contribute equally in prediction of mortality.

Single versus multiple courses of antenatal betamethasone and neonatal outcome: a randomized controlled trial.

OBJECTIVES: This study compared the beneficial and adverse neonatal effects of a single versus repeated courses of antenatal betamethasone. SETTING: Tertiary care hospital DESIGN: Open labeled, randomized controlled trial. PARTICIPANTS: Pregnant women (26-33 weeks) at risk of preterm delivery, who received one course of antenatal betamethasone and remained undelivered for 7 days.Those with uncertain gestation, major malformations and frank chorioamnionitis were excluded. INTERVENTIONS: Subjects were randomized to receive weekly antenatal betamethasone until 34 weeks or no further betamethasone. OUTCOME MEASURES: Primary: incidence of severe respiratory distress syndrome (RDS). Secondary: incidence of non-severe RDS and other neonatal morbidity; birth weight, length and occipito-frontal circumference (OFC); and, development and growth at 6 mo corrected age. RESULTS: 38 subjects were allocated to each group. Severe RDS was similar in multiple and single course groups (7% vs. 3% respectively, P=0.34), as was incidence of other morbidity. Composite outcome of RDS and or death within 28 days tended to be less in multiple course group (P=0.07). Birth anthropometry was similar in the 2 groups. At 6 mo corrected age (n=44), weight and length were significantly lower in multiple course group (p=0.003 and P=0.007, respectively), whereas OFC was not different (P=0.1). There were no differences vis a vis neurodevelopmental outcomes. CONCLUSIONS: A single course of antenatal betamethasone was as efficacious as multiple courses, with respect to prevention of neonatal morbidity. Multiple antenatal betamethasone courses have long-term adverse effects on infant weight and length growth, but not on OFC and neurodevelopment.

Evaluation of lactate dehydrogenase, creatine kinase and hepatic enzymes for the retrospective diagnosis of perinatal asphyxia among sick neonates.

It is difficult to make a retrospective diagnosis of perinatal asphyxia in symptomatic neonates delivered non-institutionally. We studied serum creatine kinase muscle-brain fraction (CK-MB), lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (SGOT) and glutamic pyruvate transaminase (SGPT) for differentiating asphyxiated (n=25) from non-asphyxiated (n=20) neonates who present with non-specific signs of sickness. CK-MB was assayed at 8 and 24 h; and LDH, SGOT and SGPT at 72 h of life. On comparing cases and controls, median 8-hr CK-MB [80 U/L vs. 26 U/L respectively, P< 0.001], median 24-hr CK-MB [33.5 U/L vs. 21.5 U/L respectively, P=0.009] and median LDH [965 U/L vs. 168 U/L respectively, P< 0.001] were higher in asphyxiated neonates. Raised LDH had 100% sensitivity, while CK-MB had 100% specificity for asphyxia. LDH had the highest area under ROC curve (0.998). We conclude that LDH at 72 hr of life is most accurate at differentiating asphyxiated from non-asphyxiated symptomatic neonates.

Retinopathy of prematurity in Asian Indian babies weighing greater than 1250 grams at birth: ten year data from a tertiary care center in a developing country.

BACKGROUND: Retinopathy of prematurity (ROP) is an important cause of childhood blindness in developing countries. AIM: To report the spectrum of ROP and associated risk factors in babies weighing > 1250 g at birth in a developing country. SETTING AND DESIGN: Institutional, retrospective, non-randomized, observational clinical case series. MATERIALS AND METHODS : Retrospective analysis (10 years) of 275 eyes (138 babies) with ROP. STATISTICAL ANALYSIS: Qualitative data with the Chi-square test. Quantitative data using the unpaired t test or the ANOVA and further tested using multivariate logistic regression. RESULTS: The mean birth weight was 1533.9 g (range 1251 to 2750 g) and the mean period of gestation was 30.9 weeks (range 26 to 35). One hundred and twenty-four of 275 eyes (45.1%) had threshold or worse ROP. Risk factors for threshold or worse disease were, 'outborn babies' ( P P = 0.007) and exchange transfusion ( P = 0.003). The sensitivity of the American and British screening guidelines to pick up threshold or worse ROP in our study group was 82.4% and 77.4% respectively. CONCLUSIONS : Severe ROP is often encountered in babies weighing greater than 1250 g at birth in developing countries. Western screening guidelines may require modifications before application in developing countries.

Multiple courses of antenatal steroids.

The benefits and risks of multiple courses of antenatal steroids (ANS) are still unresolved issues. This was a prospective cohort study in a level III neonatal unit. Preterm babies < or = 35 wk gestation were included. Malformations, chronic maternal steroid intake, exchange transfusions prior to cortisol sampling and incomplete ANS courses were exclusion criteria. Subjects were classified into: No course (Group 0), 1 course (group 1), 2 courses (Group 2), > 2 courses (Group 3) of antenatal dexamethasone. The key outcome was adrenal function assessed by basal and post-ACTH cortisol on day 3. Other outcomes were neonatal morbidity, mortality, growth parameters at birth, long term growth and neuro-development. Of 210 eligible babies, 124 were enrolled. 38, 51, 10 and 25 babies belonged to groups 0, 1, 2 and 3 respectively. Basal and post-ACTH serum cortisol did not show any significant difference between groups (p=0.5 and p=0.9 respectively). Incidence of severe HMD requiring ventilation was significantly lower (p=0.02) in multiple course group (combined groups 2 and 3) compared to single course group. There were no differences in other neonatal morbidity, birth OFC and weight between single and multiple ANS groups. Follow up data at a mean age of 22 mth was available in 59 subjects (69%) belonging to groups 1-3. No differences were noted in the proportion of patients with abnormal neurological examination (p=0.1), abnormal PDI (p=0.9), abnormal MDI (p=0.9) and physical growth between multiple and single course groups. Multiple courses of antenatal dexamethasone resulted in a significant decrease in severe forms of RDS and they did not cause adrenal suppression, decreased growth or impaired neuro-development.

Randomized controlled trial of compact fluorescent lamp versus standard phototherapy for the treatment of neonatal hyperbilirubinemia.

BACKGROUND: Special blue tube lights of standard length are used in most neonatal units to deliver phototherapy. Of late, special blue compact fluorescent lamp phototherapy equipments have been introduced in India, which are claimed to be better than standard tube lights. AIM: To compare special blue compact fluorescent lamp (CFL) phototherapy with special blue standard-length tube lights (STL). METHODS: This randomized, controlled trial was conducted in a level III NICU. Neonates, otherwise healthy, of gestation greater than 34 weeks with hyperbilirubinemia requiring phototherapy, were included. Rh iso-immunized babies, those who underwent prior exchange transfusion and whose parents declined to consent were excluded. By stratified block randomization, babies were allocated to receive phototherapy by CFL or STL. CFL and STL were both special blue lights with irradiance maintained above 15 microWatts/nm/cm2. Total serum bilirubin (TSB) was measured 12 hourly till phototherapy was stopped or an exchange transfusion was done. Temperature and clinical and laboratory parameters of dehydration were recorded 12 hourly till 72 hrs. Nursing staff answered an objectivized proforma about the disadvantageous effects on nurses. RESULTS: Fifty babies were enrolled in each group. Baseline characteristics, causes of jaundice, hemolysis, baseline TSB and irradiance were similar in both groups. Mean duration of phototherapy (P = 0.98) was similar in both groups. Kaplan-Meier analysis of phototherapy duration showed no difference in the survival curves of the 2 groups (P = 0.6). Axillary temperature was similar in both groups and no baby was dehydrated. Nursing staff reported no significant differences between CFL and STL visavis glare hurting the eyes, giddiness and headache. CONCLUSIONS: CFL phototherapy has no superiority over STL phototherapy in terms of efficacy and adverse effects on the neonate and effects on nursing staff.

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.

Cost of neonatal intensive care in a tertiary care center.

BACKGROUND: The number of neonatal intensive care units (NICUs) in India has increased substantially over the last decade; yet many more are required. There is limited information on the actual costs of setting up and running an NICU in India. OBJECTIVE: Systematic and comprehensive calculation and analysis of the costs of neonatal intensive care in a tertiary care teaching hospital. METHODS: The costs were compiled by studying the detailed records of various hospital departments and prospectively documenting the costs of drugs, consumables and investigations for a representative group of 30 babies. RESULTS: The total cost of establishing a 16 bed level III tertiary care NICU was Rs 3.78 crore (Rs. 37.8 million, USdollar 860,000) (2003). Equipment cost formed two-thirds of the establishment cost. The running cost of NICU care per patient per day was Rs 5450 (USdollar 125). NICU and ancillary personnel salary comprised the largest proportion of the running costs. The average total cost of care for a baby less than 1000 grams was Rs. 168000 (USdollar 3800), Rs. 88300 (USdollar 2000) for babies 1000 g to 1250 g. and Rs. 41700 (USdollar 950) for those between 1250 to 1500 g. The family had to bear only 25 percent; rest was subsidized. CONCLUSIONS: Equipment and personnel salary form the biggest proportion of establishment and running costs. The costs of treatment for a baby in NICU should be seen in context with costs of other types of health care and the number of useful life years gained.

Early onset neonatal sepsis due to Morganella morganii.

Two neonates, both 32-weekers, developed Morganella morganii sepsis on the first day of life. They presented within a day of each other, primarily with respiratory signs. In both cases there was a history of spontaneous premature rupture of membranes, exposure to a single dose of ampicillin ante-partum, and similar antibiograms. No common source could be identified.

Multiple dose pharmacokinetics of ciprofloxacin in preterm babies.

BACKGROUND: Ciprofloxacin is increasingly used in preterm neonates to treat multi-drug resistant infections, however the pharmacokinetics of this drug in preterm newborns is not well studied. OBJECTIVES: To determine the multi-dose pharmacokinetics of intravenous ciprofloxacin in pre-term infants. DESIGN: Prospective, cohort study. SETTING: Level III Neonatal Intensive Care Unit in a tertiary Care hospital in North India. METHODS: 24 preterm neonates with age < 28 days, who received intravenous ciprofloxacin 10 mg/kg/dose 12 hourly for clinical and/or culture proven sepsis, were enrolled. Serum levels of ciprofloxacin were analyzed after first dose on day 1 and at the end of days 3 and 7. Results: Of 24 babies included in the study [mean gestation (SD) 32 wks (2.4 wks)], 3 died and 1 dropped out in the initial few days, leaving 20 patients whose data on serum ciprofloxacin were available. Peak values on days 1, 3 and 7 were [mean +/- SEM] 2.3 +/- 0.39 microg/mL, 3.0 +/- 0.44 microg/mL and 2.7 +/- 0.39 microg/mL respectively (P >0.05). Trough values on these days were 0.7 +/- 0.14 microg/mL 0.8 +/- 0.14 microg/mL and 1.0 +/- 0.21 microg/mL respectively (P > 0.05). There were no differences between the <1500 g and > 1500 g sub-groups and the < 7 days and >7 days sub-groups with respect to the corresponding peak and trough values on days 1, 3 and 7. The 95% C.I. of serum concentrations were above the MIC90 for most Enterobacteriaceae species, however the lower bound of the 95% C.I. of the mean trough levels was lower than MIC90 for Pseudomonas aeruginosa and Staphylococcus aureus. No adverse effects were observed. CONCLUSIONS: Intravenous ciprofloxacin in a dose of 10 mg/kg/dose 12 hourly is an effective treatment of neonatal sepsis, but higher doses may be required for treating Staphylococcus aureus and Pseudomonas.

Risk factors of threshold retinopathy of prematurity.

OBJECTIVE: To determine the risk factors which predispose to the development of threshold retinopathy of prematurity among patients of retinopathy of prematurity. METHODS: The ROP clinic records of a 3 year period were retrospectively studied to identify babies with threshold ROP (T-ROP) and sub-threshold ROP (ST-ROP). Various antenatal and perinatal risk factors, neonatal morbidity and therapeutic interventions were compared between the 2 groups. RESULTS: Of the total of 108 babies, 55 had T-ROP and 53 had ST-ROP. On univariate analysis, packed cell transfusions for anemia, double volume exchange transfusions (DVET), number of DVET, ventilation, gestational age <or= 28 weeks and apneic episodes were significantly higher in the T-ROP group. On multivariate analysis, the administration of packed cells [OR 2.8, 95 PERCENT CI 1.2, 6.6; (p = 0.014)] and DVET [OR 2.7, 95 PERCENT CI 1.2, 6.5; (p = 0.022)] emerged as independent risk factors of T-ROP. CONCLUSION: Administration of blood products increases the risk of developing T-ROP among patients who have ROP. There is a need to exercise caution in the use of blood products in premature newborns.

Cutaneous Aspergillus flavus infection in a neonate.

A premature newborn infant born at 30 weeks gestation developed erythematous papular skin lesions that coalesced to form a necrotic plaque with black eschar. Skin histopathology and culture demonstrated infection with Aspergillus flavus. There was no evidence of Aspergillus flavus infection elsewhere.

Subgaleal hematoma and seven exchange transfusions.

A 3 kg baby was delivered by cesarean section after prolonged labor. He had massive subgaleal hematoma. He developed anemia requiring packed cell transfusions and hyperbilirubinemia requiring a total of seven exchange transfusions and highly intensive phototherapy. There were no adverse complications of the hyperbilirubinemia or the exchange transfusion.

Research in neonatology: need for introspection.

This study was conducted to evaluate the quality of neonatal research published in major Indian journals. Four indexed Indian journals were scanned for topics pertaining to neonatology and the manuscripts were evaluated for the most important morbidity studied and its relevance to the national need. The analytical studies were evaluated for their quality of research methodology. Approximately 12% studies were pertaining to neonates and only one third of them were investigative in nature. Less than 20% studies were of national interest and only 5% of the total studies were community based. Although aims of the studies were clearly defined in 81%, sample size estimation was done in only 11%, blinding in 15% and one or more category of bias was seen in 84% of the studies. We conclude that there is an urgent need for interventional and community based studies in neonatology, on issues of national interest. A need was felt for improvement in the quality of research in neonatology with special emphasis on training in clinical epidemiology.