Comparison of conventional, immunological and molecular techniques for the diagnosis of symptomatic congenital human cytomegalovirus infection in neonates and infants.

Purpose: Human cytomegalovirus (HCMV) is the commonest pathogen causing congenital infection globally. The diagnosis of congenital infection is based either on viral isolation (in cell culture) or demonstration of HCMV DNA from the urine. Saliva is also being used as an alternative sample to urine for the same. The objective of this study was to compare the following assays-polymerase chain reaction (PCR) from urine, saliva and blood, serology (anti-HCMV IgM) and antigen detection (HCMV pp65 antigenaemia) for the diagnosis of congenital HCMV infection. Materials and Methods: Urine and blood samples were collected from 31 infants (median age: 13 weeks) with suspected HCMV infection. For 18 infants, additional saliva samples were collected and all the above assays were compared. Results: PCR for HCMV DNA from urine and anti-HCMV IgM were performed for all 31 infants. Of these, 22 (70.9%) were positive for both assays. In 18 (of the 22) infants positive by both assays, PCR for HCMV DNA from saliva was positive in all 18 (100%), PCR from blood in 7/18 (38.8%) and HCMV pp65 antigenaemia only in 1/18 (5.5%) of the infants. Conclusion: Detection of HCMV DNA in urine combined with anti-HCMV IgM are suitable assays to diagnose HCMV infection in infants. Both PCR from the blood and HCMV pp65 antigenaemia lack sensitivity in infants. Salivary PCR combines convenience with high sensitivity and can substitute PCR from urine, especially in the outpatient and fi eld settings. To the best of our knowledge, this is the fi rst study from India to evaluate salivary PCR for the diagnosis of congenital HCMV infection.

Cesarean section for suspected fetal distress, continuous fetal heart monitoring and decision to delivery time.

OBJECTIVE: To find out the efficacy of continuous fetal heart monitoring by analyzing the cases of cesarean section for nonreassuring fetal heart in labor, detected by cardiotocography (CTG) and correlating these cases with perinatal outcome. To evaluate whether a 30 minute decision to delivery (D-D) interval for emergency cesarean section influences perinatal outcome. METHODS: This was a prospective observational study of 217 patients who underwent cesarean section at > or = 36 weeks for non-reassuring fetal heart in labor detected by CTG. The maternal demographic profile, specific types of abnormal fetal heart rate tracing and the decision to delivery time interval were noted. The adverse immediate neonatal outcomes in terms of Apgar score <7 at 5 minutes, umbilical cord thornH <7.10, neonates requiring immediate ventilation and NICU admissions were recorded. The correlation between non-reassuring fetal heart, decision to delivery interval and neonatal outcome were analyzed. RESULTS: Out of 3148 patients delivered at > or = 36 weeks, 217 (6.8%) patients underwent cesarean section during labor primarily for non-reassuring fetal heart. The most common fetal heart abnormality was persistent bradycardia in 106 (48.8%) cases followed by late deceleration in 38 (17.5%) cases and decreased beat to beat variability in 17 (7.8%) cases. In 33 (15.2%) babies the 5 minutes Apgar score was <7 out of which 13 (5.9%) babies had cord thornH <7.10. Thirty three (15.2%) babies required NICU admission for suspected birth asphyxia. Rest 184 (84.7%) neonates were born healthy and cared for by mother. Regarding decision to delivery interval of < or =30 minutes versus >30 minutes, there was no significant difference in the incidence of Apgar score <7 at 5 minutes, cord pH <7.10 and new born babies requiring immediate ventilation. But the need for admission to NICU in the group of D-D interval < or = 30 minutes was significantly higher compared to the other group where D-D interval was >30 minutes. CONCLUSION: Non-reassuring fetal heart rate detected by CTG did not correlate well with adverse neonatal outcome. There was no significant difference in immediate adverse neonatal outcome whether the D-D time interval was < or = 30 minutes or >30 minutes; contrary to this, NICU admission for suspected birth asphyxia in </= 30 minutes group was significantly higher.

Efficacy of two dose regimes of intravenous immunoglobulin in Rh hemolytic disease of newborn--a randomized controlled trial.

OBJECTIVE: To compare the effect of two dose regimes of IVIg (0.5 g/kg vs. 1g/kg given soon after birth) on duration of phototherapy in Rh-isoimmunized neonates 32 week and above gestation. DESIGN: Randomized controlled trial. SETTING: Tertiary care hospital. SUBJECTS: Rh positive blood group neonates of gestation 32 weeks and above born to Rh negative mothers having positive Direct Coombs test and without any major malformation. INTERVENTION: Intravenous immunoglobulin (IVIg) infusion over 2 h either 0.5 g/kg (low dose group, n=19) or 1.0 g/kg (high dose group, n=19). PRIMARY OUTCOME VARIABLE: Duration of phototherapy. RESULTS: The mean duration of phototherapy was 77.3+/-57.2 h in low dose group versus 55.4+/-49 h in high dose group (mean difference=21.9; 95% CI-13.1 to 56.9). There was no difference in need for exchange transfusion (21% in both the groups) and requirement of packed red blood cells transfusion (12 transfusions in both groups). The duration of hospital stay was similar [8.4+/-6.9 and 13.6+/-14.8 days, respectively (mean difference=-5.1; 95% CI-12.8 to 2.5)]. No adverse effects of IVIg administration were noted. CONCLUSION: Two regimens of IVIg (0.5 g/Kg or 1 g/Kg) had comparable effect on duration of phototherapy, duration of hospital stay and exchange transfusion requirement, in Rh isoimmunized neonates of gestation 32 weeks and above.

Clinicoepidemiological profile and predictors of severe illness in young infants (< 60 days) reporting to a hospital in North India.

OBJECTIVES: To describe the clinical and epidemiological profile of young infants reporting to a hospital and assess previously proposed simple clinical signs for their value in enabling health workers to detect young infants with severe illness warranting hospital admission. METHODS: Observational study of infants less than 2 months of age presenting consecutively to a large public hospital in South Delhi who were evaluated by a health worker (nurse), on a standardized list of signs and symptoms, and the ability of these were evaluated against the need for hospital admission which was assessed by an independent pediatrician. RESULTS: Of the 1624 young infants triaged, 878 were enrolled into the study. Of these 100 (11%) were below 7 days of age, for whom the common reasons for seeking care were jaundice (52%), not feeding well (6%) and fever (5%). The remaining 778 (89%) were 7-59 days of age with respiratory symptoms as the main presenting complaints (29.1%). The primary clinical diagnoses in infants with serious illness needing admission to hospital in the age group <7 days (n = 66) were hyperbilirubinemia (56%) and sepsis (21%). In those between 7-27 days of age (n = 60), primary diagnoses were sepsis (27%), pneumonia (13%), diarrhea, dysentery or dehydration (10%), while in the age group 28-59 days of age (n = 47) pneumonia (40%), sepsis (19%) and diarrhea or dehydration (13%) were the common primary diagnoses. Signs that had at least a prevalence of 5% and were strong predictors for all the age categories studied were history of difficult feeding (OR 6.8 for 0-6 days, 15.1 for 2-27 days and 6.2 for 28-59 days age groups), not feeding well on observation (OR 13.7, 27.6 and 20.9 respectively for the 3 age groups), temperature > 37.5C (OR 21.8, 14.6 and 30.0 respectively for the 3 age groups) and respiratory rate > 60 per minute (OR 6.8, 15.1 and 21.0 respectively for the 3 age groups). Additional strong predictors with > 5% prevalence were history of convulsions (OR 7.9, only in 0-6 day age group), lethargy (OR 26.1, only in 7-27 day age group), and history of diarrhea (OR 3.0 for 2-27 days and 2.2 for 28-59 days age groups). CONCLUSIONS: Simple clinical signs are useful in hands of health worker for identifying neonates with serious illness warranting hospital admission. These will be of use in the further development of clinical algorithms for the national integrated management of childhood illnesses.

Clinical significance of airways colonization with Ureaplasma urealyticum in premature (<34 wk) neonates.

BACKGROUND & OBJECTIVE: Ureaplasma urealyticum has been implicated in various neonatal morbidities in preterm infants. Its association with chronic lung disease (CLD) remains controversial. The aim of this prospective study was to investigate colonization of U. urealyticum in preterm infants (with gestational age <34 wk) and to evaluate the relationship between U. urealyticum colonization and neonatal morbidity including CLD. METHODS: U. urealyticum was cultured from nasopharyngeal or endotracheal aspirates collected within 24 h of birth from infant <or=34 wk gestation weighing <1800 g admitted to a Neonatal Intensive Care Unit of a tertiary care hospital in north India, and PCR was performed on the DNA extracted from these samples. RESULTS: Twenty per cent of the study infants were colonized with U. urealyticum. The mean gestational age of the infants in the colonized group was less than that of non colonized infants (P<0.05). The peripheral total leukocyte counts and mortality rate were higher in infants with U. urealyticum colonization than in non-colonized infants (P<0.05). There was no significant difference between the colonized and non colonized groups with regard to the antenatal use of steroids, sex, cause of respiratory distress, use of surfactant, duration of ventilation. INTERPRETATION & CONCLUSION: None of the 20 babies colonized with U. urealyticum developed CLD as compared with two (2.5%) of the non colonized group. Colonization of the airways with U. urealyticum had no significant role in development of CLD in Indian preterm infants.

Maternal antenatal profile and immediate neonatal outcome in VLBW and ELBW babies.

OBJECTIVE: To evaluate the antenatal profile of the mother and the immediate neonatal morbidity and mortality till discharge. METHODS: The study was a retrospective analysis of 92 patients of preterm labour who delivered babies weighing RESULTS: A total of 92 mothers in preterm labour at 26 to 34 weeks were admitted and subsequently delivered 70 VLBW babies (< 1500 gms) and 36 ELBW babies (< 1000 gms) including 8 pairs of twins and 3 triplets pregnancies. Majority of the patients (93.4%) were booked. Amongst the various high risk factors for preterm labour, anaemia during pregnancy (32.6%), bacterial vaginosis (26%), gestational hypertension (18.4%) and pervious history of preterm labour (18.4%) were common associations. Calcium channel blocker (Depin) tocolysis was effective in postponing labour from 48 hours to more than 2 weeks. The cesarean section rate was very high (67.3%) in our study. The commoner neonatal complications in both VLBW and ELBW babies were RDS, neonatal jaundice and sepsis. Features of IUGR were seen in both the groups (22.8% in VLBW and 22.2% in ELBW babies). The neonatal mortality rate till discharge was 15.7% in VLBW group and 33.3% in ELBW group. The morality rate was highest in 26 to 30 weeks gestation babies and in babies weighing < 800 gms. CONCLUSION: Antenatal profile of preterm labour in our series showed a number of high risk factors. The identification of common high risk factors is important for appropriate prenatal care. A better neonatal survival rate was possible due to timely intervention, appropriate management and NICU care facility available in our tertiary care centre.

Incidence of periventricular leucomalacia among a cohort of very low birth weight neonates(< 1500 g).

BACKGROUND: Periventricular leucomalacia (PVL) is the most important neuropathologic lesion underlying major neuro-motor deficits of pre-term very low birth weight (VLBW) infants. Published data regarding PVL is not available from our country. OBJECTIVES: A study was planned with main objectives to estimate incidence and describe natural history of PVL among a very low birth weight cohort. STUDY DESIGN: A cohort study was performed on inborn VLBW babies over one year period at a tertiary neonatal intensive care unit. Serial weekly cranial ultrasounds were performed on 97 enrolled subjects until discharge, to diagnose and describe natural history of PVL. RESULTS: 31 out of 97 enrolled subjects developed PVL. No case of PVL developed beyond 19 days of postnatal life. Serial ultrasounds for each baby were tracked until discharge or death. Majority of lesions at onset were flares. Cysts tended to develop in over one third of cases during course of hospital stay. About 50% of ultrasound had normalized at discharge and sequelae such as cerebral atrophy and ventriculomegaly had appeared in few, the rest of lesions being either flares or cysts of PVL. CONCLUSIONS: PVL is fairly common among very low birth weight neonates. Ultrasonographic lesions of PVL undergo dynamic evolution from time of first detection to either progress, regress or leave sequelae before discharge. Ultrasound remains an important bedside diagnostic tool for PVL.

Congenital stridor due to bilateral vocal cord palsy.

Congenital stridor is one of the rare presentations of respiratory distress at birth. The commonest cause of congenital stridor is laryngomalacia, which accounts for 60% of the causes. The other common causes are congenital subglottic stenosis and vocal cord palsy (VCP). VCP is usually unilateral and most often linked with birth trauma, and is temporary. Bilateral palsy can be associated with other congenital anomalies. The current report describes a case of congenital bilateral VCP, not related to birth trauma and severe enough to require tracheostomy.

Continuous positive airway pressure - a gentler approach to ventilation.

Continuous positive airway pressure (CPAP) has become a useful modality in management of respiratory distress, especially in preterm babies. Main indications for use of CPAP are respiratory distress syndrome (RDS) and apnea of prematurity. It decreases the need of invasive and costly mechanical ventilation. This review details the physiological effects of CPAP, its methods of delivery, and its need in a country like India. It also describes the guidelines for initiating and weaning CPAP. The review concludes that use of CPAP in respiratory distress syndrome is associated with lower rates of failed treatment, decreased incidence of chronic lung disease and lower overall mortality, specially in infants with birth weight above 1500 grams. Early use of CPAP is more beneficial, Surfactant and CPAP act in conjunction for babies with RDS. CPAP is a low-cost, simple and noninvasive option for a country like India, where most places lack facilities of mechanical ventilation. Systematic reviews, randomized and quasi-randomized trials by searching MEDLINE and the Cochrane Library formed the basis of this update.

Early neonatal hyperbilirubinemia using first day serum bilirubin level.

OBJECTIVE: To evaluate the predictive value of total serum bilirubin (TSB) < or =6 mg/dl at 24 +/- 6 hr postnatal age in identifying near term and term infants, who do not develop hyperbilirubinemia subsequently. DESIGN: Prospective study. SETTING: Tertiary care hospital. METHODS: All healthy neonates with gestation > or =35 weeks, in absence of significant illness or Rh hemolysis were included. TSB was estimated at 24 +/- 6 hr by micromethod using spectrophotometry. Infants were followed up clinically every 12 hr till discharge and then after 48 hr. TSB level was estimated again whenever clinical suspicion of jaundice exceeded 10 mg/dl. Primary outcome was defined as presence of hyperbilirubinemia (TSB > or= 17 mg/dl) till day five of age. RESULTS: Of the 220 infants, 213 (96.8%) were followed up. All infants were exclusively breastfed. Mean age at bilirubin estimation was 24.7 +/- 1.9 hr with mean TSB of 5.9 +/- 1.8 mg/dl. Clinically detectable jaundice was present in 164 (77%) and hyperbilirubinemia occurred in 22 (10.3%) infants. A TSB level of < or = 6 mg/dl at 24 +/- 6 hr was present in 136 (63.8%) infants and only one infant developed hyperbilirubinemia subsequently (probability < 1%). In the remaining 77 (36.1%) infants, with TSB >6 mg/dl, subsequent hyperbilirubinemia developed in 21 (27.2%) (sensitivity 95%, specificity 70.6%, positive predictive value 27.2%, negative predictive value 99.3%, likelihood ratio of positive test 3.23 and likelihood ratio of negative test 0.07). Babies with TSB levels higher than 6 mg/dl had a significant risk of developing hyperbilirubinemia (relative risk 38; 95% confidence interval 6-1675). CONCLUSION: A TSB level of < or = 6 mg/dl at 24 +/- 6 hr of life predicted neonates who would not develop hyperbilirubinemia.

Minimal enteral nutrition.

Although parenteral nutrition has been used widely in the management of sick very low birth weight (VLBW) infants, a smooth transition to the enteral route is most desirable. Animal studies have shown that long periods of starvation are associated with mucosal atrophy and reduction of enzymatic activity. Studies have shown that giving small volumes of feeds frequently exerts a trophic effect on the gut mucosa. This concept has been termed as Minimal Enteral Nutriton (MEN). Clinical benefits of MEN include faster progression to full enteral feeds, lesser episodes of feed intolerance and reduction in hospital stay without a concomitant increase in the risk of necrotizing enterocolitis. MEN may be commenced in neonates on ventilation and total parenteral nutrition. A protocol for giving MEN has been described.

Fluid and electrolyte management in term and preterm neonates.

Disorders of fluid and electrolyte are common in neonates. Proper understanding of the physiological changes in body water and solute after birth is essential to ensure a smooth transition from the aquatic in utero environment. The newborn kidney has a limited capacity to excrete excess water and sodium and overload of fluid or sodium in the first week may result in conditions like necrotizing enterocolitis and patent ductus arteriosus. The beneficial effect of fluid restriction on the neonatal morbidity has been shown in multiple clinical trials. Simple measures like use of transparent plastic barriers, caps and socks are effective in reducing insensible water loss. Guidelines for the management of fluids according to birth weight, day of life and specific clinical conditions are provided in the protocols.

Management of infants with intra-uterine growth restriction.

Intra-uterine growth restriction (IUGR) and prematurity are the two causes for delivery of low birth weight infants. In India, IUGR contributes to almost two-thirds of infants in this category. Poor nutritional status and frequent pregnancies are common pre-disposing conditions in addition to obstetric and medical problems during pregnancy. Growth restriction may be symmetrical or asymmetrical depending on the time of insult during pregnancy. The pathological insult in an asymmetrical IUGR occurs during the later part of the pregnancy and has a brain-sparing effect. Common morbidities are more frequent in <3rd percentile group as compared to 3rd-10th percentile group. Guidelines for management of IUGR neonates in these two groups have provided in the protocols.

Post-resuscitation management of asphyxiated neonates.

Perinatal asphyxia is one of the common causes of neonatal mortality. Data from National Neonatal Perinatal database suggest that perinatal asphyxia contributes to almost 20% of neonatal deaths in India. Failure to initiate or sustain respiration after birth has been defined as criteria for the diagnosis of asphyxia by WHO. Perinatal asphyxia results in hypoxic injury to various organs including kidneys, lungs and liver but the most serious effects are seen on the central nervous system. Levene's classification is a useful clinical tool for grading the severity of hypoxic ischemic encephalopathy. Good supportive care is essential in the first 48 hours after asphyxia to prevent ongoing brain injury in the penumbra region. Strict monitoring and prompt correction is needed for common problems including temperature maintenance, blood sugars, blood pressure and oxygenation. Phenobarbitone is the drug of choice for the treatment of convulsions.

Sepsis in the newborn.

Systemic infection in the newborn is the commonest cause of neonatal mortality. Data from National Neonatal Perinatal Database 2000 suggest that Klebsiella pneumoniae and Staphylococcus aureus are the commonest causes of neonatal sepsis in India. Two forms of clinical presentations have been identified. Early onset sepsis, probably related to perinatal risk factors, usually presents with respiratory distress and pneumonia whthin 72 hours of age. Late onset sepsis, related to hospital acquired infections, usually presents with septicemia and pneumonia after 72 hours of age. Clinical features of sepsis are non-specific in neonates and a high index of suspicion is required for the timely diagnosis of sepsis. Although blood culture is the gold standard for the diagnosis of sepsis, reports are available after 48-72 hours. A practical septic screen for the diagnosis of sepsis has been described and some suggestions for antibiotic use have been included in the protocols.