Neurodevelopmental Outcomes of Very Low Birth Weight Infants at 18-24 Months, Corrected Gestational Age in a Tertiary Health Centre: A Prospective Cohort Study.

OBJECTIVE: To determine the prevalence and risk factors for poor neurodevelopmental outcome in a cohort of very low birth weight (VLBW) infants. SUBJECTS AND METHODS: Four hundred and twenty-two infants of a total of 643 VLBW survivors from a teaching hospital in South India were followed up to assess their neurodevelopmental outcomes. RESULTS: Among the 422 children who completed the assessment, results of 359 children whose assessments were done between 18 and 24 months were analysed. Thirty-seven children (10.31%) had poor neurodevelopmental outcome, six children [1.67%] had cerebral palsy, one child had visual impairment and another had hearing impairment. Poor post-natal growth was independently associated with poor neurodevelopmental outcomes in the multivariate analysis (p = 0.045). Neonatal complications were not associated with the developmental outcome. CONCLUSION: Despite lower rates of neonatal complications compared with Western cohorts, significant proportion of VLBW infants had poor neurodevelopmental outcomes. Poor post-natal growth was an important determinant of the developmental outcome.

A prospective observational study comparing cardiac function of small for gestational age with appropriate for gestational age babies using serial echocardiographic studies.

BACKGROUND: Approximately 30% of babies born in India are low birth weight (LBW) and about 70% of LBW babies are small for gestational age (SGA). Though there are several trials that have evaluated cardiac function of intrauterine growth restricted (IUGR) babies in utero, there is limited data about postnatal cardiac function in SGA babies during early neonatal period. This study was conducted to evaluate the cardiac functions of SGA babies by serial echocardiographic measurements and compare this with appropriate for gestational age (AGA) babies during the early postnatal period. MATERIAL AND METHODS: Seventy babies were enrolled in this prospective observational study with 35 each in the SGA and AGA groups. Echocardiography was performed for all babies on days 1, 2, and 3 of life. Myocardial performance index (MPI) was used as the primary measure to compare cardiac function. MPI was calculated for both ventricles using pulse wave Doppler and tissue Doppler. RESULTS: MPI of the left ventricle was significantly higher in the SGA group as compared to AGA babies during all the three measurement periods with SGA babies having significantly higher MPI of right ventricle on day 1 and day 2 but not on day 3. Left ventricular internal diameter index during diastole and systole (LVIDD index and LVIDS index), left atrium: aortic root ratio (LA:AO ratio) were significantly increased in SGA babies on all the occasions. Fractional shortening, ejection fraction, and area shortening were similar in two groups. CONCLUSIONS: Myocardial performance index of left and right ventricle, which evaluates both systolic and diastolic function of ventricles, was significantly increased in SGA babies in comparison to AGA babies during the first 3 days of life except MPI of the right ventricle on day 3. Thus, SGA babies have compromised cardiac function through all phases of the cardiac cycle with the performance improving spontaneously over time.

Perinatal Risk Factors for Neonatal Early-onset Group B Streptococcal Sepsis after Initiation of Risk-based Maternal Intrapartum Antibiotic Prophylaxis-A Case Control Study.

OBJECTIVES: To identify the perinatal risk factors for early-onset Group B Streptococcus (EOGBS) sepsis in neonates after inception of a risk-based maternal intrapartum antibiotic prophylaxis strategy in 2004. DESIGN: Case control study. METHODS: All newborn with early onset GBS sepsis (born between 2004 and 2013) were deemed to be "cases" and controls were selected in a 1:4 ratio. RESULTS: More than three per vaginal (PV) examinations [odds ratio (OR) 8.57, 95% confidence interval (CI) 3.10-23.6] was a significant risk factors. Peripartum fever (OR 3.54, 95% CI 1.3-9.67), urinary tract infection (OR 2.88, 95% CI 1.08-7.63), meconium-stained amniotic fluid (MSAF) (OR 2.52, 95% CI 1.18-5.37) and caesarean section (OR 1.99, 95% CI 1.16-3.43) were also found to be associated with EOGBS sepsis. CONCLUSION: Multiple vaginal examinations are the strongest risk factors for peripartum Group B Streptococcal (GBS) sepsis. The association of MSAF and caesarean section indicates that foetal distress is an early symptom of perinatal GBS infection.

A modified technique for umbilical arterial catheterization.

A modified technique for umbilical artery catheterization was assessed in babies in whom conventional method failed or if the cord was dry. Success rate attained with the modified technique was 90% (19/21). This modified technique could provide an easier and faster method for successful umbilical arterial catheterization.

Neonatal hearing screening--experience from a tertiary care hospital in southern India.

OBJECTIVE: To implement a neonatal hearing screening program using automated auditory brainstem response audiometry in a tertiary care set-up and assess the prevalence of neonatal hearing loss. DESIGN: Descriptive study. SETTING: Tertiary care hospital in Southern India. PARTICIPANTS: 9448 babies born in the hospital over a period of 11 months. INTERVENTION: The neonates were subjected to a two stage sequential screening using the BERAphone. Neonates suspected of hearing loss underwent confirmatory testing using auditory steady state response audiometry. In addition, serological testing for TORCH infections, and connexin 26 gene was done. MAIN OUTCOME MEASURES: Feasibility of the screening program, prevalence of neonatal hearing loss and risk factors found in association with neonatal hearing loss. RESULTS: 164 babies were identified as suspected for hearing loss, but of which, only 58 visited the audiovestibular clinic. Among 45 babies who had confirmatory testing, 39 were confirmed to have hearing loss and were rehabilitated appropriately. 30 babies had one or more risk factors; 6 had evidence of TORCH infection and 1 had connexin 26 gene mutation. CONCLUSION: Neonatal hearing screening using BERAphone is a feasible service. The estimated prevalence of confirmed hearing loss was comparable to that in literature. Overcoming the large numbers of loss to follow-up proves to be a challenge in the implementation of such a program.

Perinatal outcome of infants born to diabetic mothers in a developing country--comparison of insulin and oral hypoglycemic agents.

OBJECTIVE: To study the perinatal outcomes of infants born to mothers with gestational diabetes treated with insulin or oral hypoglycemic agents in a developing country. DESIGN: Prospective observational cohort study. SETTING: Tertiary-care perinatal center in southern India. PARTICIPANTS: Babies born to mothers with gestational diabetes. METHODS: Maternal details were obtained and physical examination was performed on the neonates. Babies were given hourly feeds soon after birth and blood glucoses checked at 1, 3, 5, 9 and 12 hours of life; hematocrit and calcium levels were also measured. Perinatal outcomes were compared between mothers who required insulin or an oral hypoglycemic agent for treatment of diabetes. RESULTS: Of the 10,394 mothers who delivered during the study period, 574 (5.5%) were diagnosed to have gestational diabetes. 137 were treated with insulin and 141 with oral hypoglycemic agents. 44 (15.8%) babies were born preterm, 97 (35%) were large for gestational age, 13 (4.7%) were small for gestational age and 9 (3.2%) were macrosomic. Hypoglycemia was seen in 26 (9.3%) babies, congenital anomalies in 15 (5.4%) and birth injuries in 7 (2.5%). There was no difference between the two groups in any of the outcomes except for hyperbilirubinemia, which was more in the insulin group (13.7% vs 6.5%, P=0.04). CONCLUSIONS: There was no difference in the perinatal outcome whether the mother received insulin or an oral hypoglycemic agent for treatment of gestational diabetes other than the increased incidence of hyperbilirubinemia in the insulin group.

Microvillous inclusion disease diagnosed by gastric biopsy.

Protracted diarrhea in neonates is uncommon and usually requires an intestinal biopsy for etiological diagnosis. Gastric biopsy has not been used in the routine diagnosis of this condition. We report the first documented patient with microvillous inclusion disease from India, where the diagnosis was established by a gastric biopsy.

A randomized control trial comparing two enteral feeding volumes in very low birth weight babies.

Poor post-natal growth of preterm neonates is common and fortification is recommended. However, this is not always practical in low-resource areas. Hypothesizing that increasing the volume of feeds would be safe and lead to better post-natal weight gain, we randomized 64 babies with birth weight <1500 g, once they reached full feeds, to continue feeds at 200 ml/kg/day (standard volume) or increase to 300 ml/kg/day (high volume) of expressed breast milk. There was a significantly higher daily weight gain in the high-volume group as compared to the standard volume group (24.9 vs. 18.7 g/kg/day, p < 0.0001). There were no differences in complications like feed intolerance, tachypnoea, sepsis, patent ductus arteriosus or necrotizing enterocolitis. High-volume feeds at 300 ml/kg/day was safe and resulted in better weight gain than standard volume feeds in very low birth weight babies.

Retrospective cohort study comparing neonatal outcomes of women treated with glyburide or insulin in gestational diabetes: a 5-year experience in a South Indian teaching hospital.

OBJECTIVE: To assess the effectiveness of glyburide in preventing complications of gestational diabetes in neonates as compared to insulin. MATERIALS AND METHODS: Information from birth register, maternal and neonatal records were obtained. Five hundred and seventy-seven gestational diabetics with moderate hyperglycemia i.e., with highest fasting plasma glucose value of ≤130 mg/dl and/or highest post-prandial value of ≤250 mg/dl treated with insulin or glyburide were included from a cohort of 769 women needing additional therapy to initial diet therapy during a 5-year period. Thus neonatal outcomes of 303 women treated with insulin and 274 women treated with glyburide were compared. RESULTS: Baseline plasma glucose levels in the group treated with insulin were higher. The mean birth weight (SD) of the neonates in women treated with insulin was 3021.3 g (604.19) as compared to 3104.6 g (499.35, P = 0.07) in the group treated with glyburide. Neonatal outcomes such as hypoglycemia (4.9%, 3.6%, P = 0.44), hypocalcemia (1.3%, 0.7%, P = 0.48), polycythemia (1.7%, 0.7%, P = 0.31), macrosomia (11.6%, 8.7%, P = 0.26), congenital anomalies (2.1%, 2.3%, P = 0.87), birth trauma (1.4%, 1.2%, P = 0.79) were similar in both groups. Neonates of women treated with insulin were more likely to have hyperbilirubinemia (11.5%, 6.5%, P = 0.03). CONCLUSION: Neonatal outcomes of women treated with glyburide were comparable to those in women treated with insulin. More number of neonates of mothers treated with insulin had hyperbilirubinemia compared to neonates of mothers treated with glyburide (11.5%, 6.5% P = 0.03).

Whole body cooling in newborn infants with perinatal asphyxial encephalopathy in a low resource setting: a feasibility trial.

OBJECTIVE: To determine the feasibility and safety of whole body cooling in newborn infants with perinatal asphyxial encephalopathy in a low resource setting. DESIGN: Feasibility trial. SETTING: Tertiary care perinatal centre. SUBJECTS: Infants born at > 35 weeks gestation with perinatal asphyxia were included in the study. INTERVENTIONS: Infants were cooled to a rectal temperature of 33 ± 0.5°C for 72 hours using cloth-covered ice-gel packs. Vital parameters were monitored continuously. OUTCOME MEASURES: The primary outcome was the achievement of target temperature within 1 hour of initiation of treatment and maintaining the target temperature for 72 hours. Adverse events and possible complications of hypothermia were the secondary outcomes measured. RESULTS: Twenty infants were included in the study. The mean time taken to achieve target rectal temperature was 52 ± 25 minutes. The mean rectal temperature during cooling was 32.9 ± 0.11ºC. The target temperature could be maintained for 72 hours without difficulty in all babies. Adverse events observed during cooling were thrombocytopenia (25%), sinus bradycardia (25%), deranged bleeding parameters (20%), aposteatonecrosis (15%), hyperglycemia (15%), hypoglycemia (10%), hypoxemia (5%), life-threatening coagulopathy (5%) and death (5%). Shivering was noted in many of the babies, especially in the initial phase of cooling. CONCLUSION: Whole body cooling in term infants with perinatal asphyxia is achievable, safe and inexpensive in a low-resource setting.

Comparison of viral load and duration of virus shedding in symptomatic and asymptomatic neonatal rotavirus infections.

A single rotavirus strain causing asymptomatic infections as well as severe gastrointestinal disease has been described in the neonatal nurseries of the Christian Medical College, Vellore. In this study, quantitative real-time RT-PCR was used to determine the association of viral load with the presence of gastrointestinal symptoms in neonates. Viral load was estimated in terms of the crossing point [C(t) value] at which the amplicon could be detected in the real-time PCR assay. The study was carried out on 103 neonates, including 33 asymptomatic neonates and 70 neonates with different gastrointestinal symptoms. The duration of virus shedding was also compared between five symptomatic and four asymptomatic neonates using real-time RT-PCR. There was no significant difference in viral load between symptomatic and asymptomatic neonates (P = 0.087). Among neonates with different gastrointestinal symptoms, those presenting with feed intolerance and abdominal distension had a significantly higher viral load than those with other gastrointestinal symptoms (P = 0.02). For the study on virus shedding, nine neonates were followed up for a median duration of 53 days, with a median of 31 samples tested per child. Extended shedding of low copies of rotavirus was found, with no significant differences in pattern of shedding between symptomatic and asymptomatic neonates. The lack of correlation between viral load and gastrointestinal disease demonstrates yet another difference between neonatal rotavirus infection and infection in older children where higher viral load correlates with severe disease.

Genogroup IIb norovirus infections and association with enteric symptoms in a neonatal nursery in southern India.

Noroviruses (NoVs) are increasingly recognized as an important cause of acute gastroenteritis in children worldwide. However, there are limited data on the role of NoVs in neonatal infections and disease. The objectives of the present study were to determine the prevalence of NoVs in neonates with gastrointestinal disease using a case-control study design and to characterize the NoV strains infecting neonates. A total of 309 fecal samples from 161 neonates with gastrointestinal symptoms and 148 asymptomatic controls were screened for genogroup II (GII) NoV using reverse transcription-PCR. A subset of PCR-positive amplicons for the polymerase and capsid regions was sequenced. NoV was detected in 26.2% of samples, with the rate of detection being significantly higher among symptomatic neonates (60/161, 37.2%) than asymptomatic neonates (24/148, 14.1%) (P < 0.001). On the basis of sequencing of 29 strains, a single NoV strain, GIIb, was identified to be the predominant (27/29, 93.1%) cause of neonatal infections. Coinfection with rotavirus was seen in nearly one-third of symptomatic neonates. The study demonstrates a high prevalence of NoV infections in neonates and indicates that coinfection with rotavirus may result in significantly more gastrointestinal disease in this population.

Whole genome characterization of reassortant G10P[11] strain (N155) from a neonate with symptomatic rotavirus infection: identification of genes of human and animal rotavirus origin.

BACKGROUND: Rotavirus G10P[11] strains have long been associated with asymptomatic neonatal infections in some parts of India. We have previously reported G10P[11] strains associated with both asymptomatic infections and severe gastrointestinal disease in neonates from Vellore in southern India, with >90% partial nucleotide and amino acid identity to the VP4, VP6, VP7 and NSP4 genes of the exclusively asymptomatic G10P[11] strain I321. OBJECTIVES: In this study, the whole genome of a G10P[11] isolate (N155) from a neonate with severe gastrointestinal disease was characterized to determine whether there were significant differences in its genetic makeup in comparison to G10P[11] strain I321 and to establish the origin of the G10P[11] strains in Vellore. STUDY DESIGN: PCR amplification and complete genome sequencing was carried out for all 11 gene segments of symptomatic G10P[11] rotavirus isolate N155. Nucleotide and amino acid sequence similarity with I321, other human and bovine strains for each gene segment were determined. The origin of each gene was determined based on the degree of identity to bovine or human rotavirus strains. RESULTS: N155 was found to be a reassortant between human and bovine rotaviruses. With the exception of NSP2, gene sequences of strain N155 showed >90% identity to published sequences of I321. Gene segments encoding NSP1, 2 and 3 were of human rotavirus origin for both strains; however, phylogenetic analysis of NSP2 sequences indicated that the human parental strain that led to the origin of these bovine-human reassortant strains was different. There were no significant differences between NSP2 sequences of strains from symptomatic and asymptomatic neonates in the same setting. CONCLUSIONS: The study shows that the difference in clinical presentations in neonates may not be due to the limited variability in the genome sequence of G10P[11] strains and that G10P[11] strains in different parts of India could have evolved through reassortment of different parental strains.

Rotavirus infection in the neonatal nurseries of a tertiary care hospital in India.

BACKGROUND: The majority of neonatal rotavirus infections are believed to be asymptomatic, and protection from subsequent infection and disease has been reported in neonatally infected children. In this study, we present the results of a 4-year prospective surveillance in the neonatal nurseries of a tertiary care hospital in south India. METHODS: Stool samples from neonates admitted for >48 hours either with gastrointestinal (GI) symptoms or with nonenteric pathology were screened for rotavirus. Careful assessment of clinical data was carried out. G- and P-typing for all symptomatic rotavirus positive cases and equal number of asymptomatic controls from the same month was determined by reverse transcription polymerase chain reaction. RESULTS: Rotavirus was detected in 43.9% of 1411 neonates, including those with and without gastrointestinal disease. Rotavirus detection was significantly higher among neonates with GI disease (55.5%) than asymptomatic neonates (44.4%) (P < 0.001). Rotavirus was seen in association with diarrhea, vomiting, feed intolerance, necrotizing enterocolitis, hematochezia, gastroesophageal reflux, and abdominal distension. Diarrhea was significantly more frequent in neonates with rotavirus infection (P < 0.001) whereas uninfected neonates developed significantly more feeding intolerance (P < 0.001). Significantly greater proportion of term neonates with GI disease were positive for rotavirus than preterm neonates (P < 0.001). G10P[11] was the most common genotype associated with both symptomatic and asymptomatic infections. CONCLUSIONS: This study documents the high rates of rotavirus infection in the neonatal nurseries and the continuing detection of the G10P[11] strain associated with GI disease in Vellore.

Investigation of the environment and of mothers in transmission of rotavirus infections in the neonatal nursery.

A distinct feature of neonatal rotavirus infection is the association of unusual strains that appear to be prevalent only in neonatal units and persist for long periods of time. The main aims of this study were to determine if rotavirus can be detected on environmental surfaces in the neonatal nursery and whether the infection occurs in mothers of infected and uninfected neonates. Thirty rotavirus positive neonates and an equal number of negative neonates were enrolled in this study. Stool samples from 15 mothers in each group and environmental swabs collected from the bed and surfaces around neonates were tested for rotavirus using single round and nested PCR for the VP6 gene. Rotavirus could be detected in environmental swabs using single round PCR for VP6 gene in 40% of neonates positive for rotavirus antigen by enzyme immunoassay (EIA) and 33.3% of EIA negative neonates. The detection rate was almost 100% using the nested VP6 PCR. Rotavirus was detected in maternal samples only if the nested VP6 PCR was used, with no significant difference between rates of rotavirus detection in maternal fecal samples of infected and uninfected neonates (p-0.4). Sequence analysis of nested VP6 amplicons from two environmental swabs revealed them to be closest in identity to G10P[11], the most common genotype causing infections in neonates in this setting. Interestingly, sequences of amplicons from maternal stool samples did not cluster with G10P[11] or other VP6 subgroup I strains but showed clustering with human strains of VP6 subgroup II.

Determination of extended-interval gentamicin dosing for neonatal patients in developing countries.

BACKGROUND: Infectious diseases account for an estimated 36% of neonatal deaths globally. The purpose of this study was to determine safe, effective, simplified dosing regimens of gentamicin for treatment of neonatal sepsis in developing countries. METHODS: Neonates with suspected sepsis in the neonatal intensive care unit (NICU) at Christian Medical College and Hospital (CMC), Vellore, India (n = 49), and Dhaka Shishu Hospital (DSH), Bangladesh (n = 59), were administered gentamicin intravenously according to the following regimens: (1) 10 mg every 48 hours for neonates <2000 g; (2) 10 mg every 24 hours for neonates 2000-2249 g; and (3) 13.5 mg every 24 hours for neonates > or =2500 g. Serum gentamicin concentration (SGC) at steady state and pharmacokinetic indices were determined. Renal function was followed while under treatment and hearing was examined 6 weeks to 3 months after discharge. RESULTS: All neonates, except 1 weighing 2000-2249 g at DSH, had a peak SGC >4 microg/mL. Overall, 5 (10%) and 17 (29%) infants had a peak SGC level > or =12 microg/mL from CMC and DSH, respectively, and 10 (20%) and 4 (7%) cases from CMC and DSH, respectively, had a trough SGC level > or =2 microg/mL. However, no infant <2000 g had a trough SGC level > or =2 microg/mL. We found no evidence of gentamicin nephrotoxicity or ototoxicity. CONCLUSION: Safe, therapeutic gentamicin dosing regimens were identified for treatment of neonatal sepsis in developing country settings. Administration of these doses could be simplified through use of Uniject, a prefilled, single injection device designed to make injections safe and easy to deliver in developing country settings.

Neonatal hydrothorax following migration of a central venous catheter.

The use of a central venous catheter may occasionally be associated with complications like sepsis, effusions and thrombosis. Migration of the central catheter is an unusual complication that often goes unrecognized. This case report is of a neonate who developed hydrothorax resulting from a migrating central line and highlights the need for a high level of clinical suspicion in diagnosing catheter related problems.