Validation of visual estimation of neonatal jaundice in low-income and middle-income countries: a multicentre observational cohort study.

OBJECTIVE: Determine the sensitivity and specificity of neonatal jaundice visual estimation by primary healthcare workers (PHWs) and physicians as predictors of hyperbilirubinaemia. DESIGN: Multicentre observational cohort study. SETTING: Hospitals in Chandigarh and Delhi, India; Dhaka, Bangladesh; Durban, South Africa; Kumasi, Ghana; La Paz, Bolivia. PARTICIPANTS: Neonates aged 1-20 days (n=2642) who presented to hospitals for evaluation of acute illness. Infants referred for any reason from another health facility or those needing immediate cardiopulmonary resuscitation were excluded. OUTCOME MEASURES: Infants were evaluated for distribution (head, trunk, distal extremities) and degree (mild, moderate, severe) of jaundice by PHWs and physicians. Serum bilirubin level was determined for infants with jaundice, and analyses of sensitivity and specificity of visual estimations of jaundice used bilirubin thresholds of >260 µmol/L (need for phototherapy) and >340 µmol/L (need for emergency intervention in at-risk and preterm babies). RESULTS: 1241 (47.0%) neonates had jaundice. High sensitivity for detecting neonates with serum bilirubin >340 µmol/L was found for 'any jaundice of the distal extremities (palms or soles) OR deep jaundice of the trunk or head' for both PHWs (89%-100%) and physicians (81%-100%) across study sites; specificity was more variable. 'Any jaundice of the distal extremities' identified by PHWs and physicians had sensitivity of 71%-100% and specificity of 55%-95%, excluding La Paz. For the bilirubin threshold >260 µmol/L, 'any jaundice of the distal extremities OR deep jaundice of the trunk or head' had the highest sensitivity across sites (PHWs: 58%-93%, physicians: 55%-98%). CONCLUSIONS: In settings where serum bilirubin cannot be measured, neonates with any jaundice on the distal extremities should be referred to a hospital for evaluation and management, where delays in serum bilirubin measurement and appropriate treatment are anticipated following referral, the higher sensitivity sign, any jaundice on the distal extremities or deep jaundice of the trunk or head, may be preferred.

WINROP algorithm for prediction of sight threatening retinopathy of prematurity: Initial experience in Indian preterm infants.

PURPOSE: To determine the efficacy of the online monitoring tool, WINROP (https://winrop.com/) in detecting sight-threatening type 1 retinopathy of prematurity (ROP) in Indian preterm infants. METHODS: Birth weight, gestational age, and weekly weight measurements of seventy preterm infants (<32 weeks gestation) born between June 2014 and August 2016 were entered into WINROP algorithm. Based on weekly weight gain, WINROP algorithm signaled an alarm to indicate that the infant is at risk for sight-threatening Type 1 ROP. ROP screening was done according to standard guidelines. The negative and positive predictive values were calculated using the sensitivity, specificity, and prevalence of ROP type 1 for the study group. 95% confidence interval (CI) was calculated. RESULTS: Of the seventy infants enrolled in the study, 31 (44.28%) developed Type 1 ROP. WINROP alarm was signaled in 74.28% (52/70) of all infants and 90.32% (28/31) of infants treated for Type 1 ROP. The specificity was 38.46% (15/39). The positive predictive value was 53.84% (95% CI: 39.59-67.53) and negative predictive value was 83.3% (95% CI: 57.73-95.59). CONCLUSION: This is the first study from India using a weight gain-based algorithm for prediction of ROP. Overall sensitivity of WINROP algorithm in detecting Type 1 ROP was 90.32%. The overall specificity was 38.46%. Population-specific tweaking of algorithm may improve the result and practical utility for ophthalmologists and neonatologists.

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]. CONCLUSION: 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 infants 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 fathers age, occupation and education independently predicted stress. CONCLUSION: Fathers of preterm infants admitted in hospital are stressed, primarily due to financial burden.

Etiology of bacteremia in young infants in six countries.

BACKGROUND: Neonatal illness is a leading cause of death worldwide; sepsis is one of the main contributors. The etiologies of community-acquired neonatal bacteremia in developing countries have not been well characterized. METHODS: Infants <2 months of age brought with illness to selected health facilities in Bangladesh, Bolivia, Ghana, India, Pakistan and South Africa were evaluated, and blood cultures taken if they were considered ill enough to be admitted to hospital. Organisms were isolated using standard culture techniques. RESULTS: Eight thousand eight hundred and eighty-nine infants were recruited, including 3177 0-6 days of age and 5712 7-59 days of age; 10.7% (947/8889) had a blood culture performed. Of those requiring hospital management, 782 (54%) had blood cultures performed. Probable or definite pathogens were identified in 10.6% including 10.4% of newborns 0-6 days of age (44/424) and 10.9% of infants 7-59 days of age (39/358). Staphylococcus aureus was the most commonly isolated species (36/83, 43.4%) followed by various species of Gram-negative bacilli (39/83, 46.9%; Acinetobacter spp., Escherichia coli and Klebsiella spp. were the most common organisms). Resistance to second and third generation cephalosporins was present in more than half of isolates and 44% of the Gram-negative isolates were gentamicin-resistant. Mortality rates were similar in hospitalized infants with positive (5/71, 7.0%) and negative blood cultures (42/557, 7.5%). CONCLUSIONS: This large study of young infants aged 0-59 days demonstrated a broad array of Gram-positive and Gram-negative pathogens responsible for community-acquired bacteremia and substantial levels of antimicrobial resistance. The role of S. aureus as a pathogen is unclear and merits further investigation.

Comparison of stool colonization in premature infants by three dose regimes of a probiotic combination: a randomized controlled trial.

OBJECTIVE: To compare stool colonization among premature infants receiving high-dose probiotics versus standard dose. STUDY DESIGN: This blinded, randomized, placebo-controlled trial was conducted in a Level III neonatal unit. Eligibility criteria were gestational age 27-33 weeks, age < 96 hours, tolerating milk ≥ 15 mL/kg/day and availability for follow-up. Gastro-intestinal/life-threatening malformations and necrotizing enterocolitis/sepsis were exclusions. A total of 149 subjects were randomly allocated to groups A through D (received 12-hourly probiotic supplements of 10(10) cells for 21 days, 10(10) cells for 14 days, 10(9) cells for 21 days and placebo, respectively). Key outcome was stool colonization by a probiotic organism at 28 days. RESULTS: Colonization with Lactobacillus and Bifidobacterium was significantly higher in groups A, B, and C versus placebo respectively, but groups A through C did not differ from each other. There were trends toward more colony forming unit (cfu) of Lactobacillus and Bifidobacterium per milliliter of stool in group A versus B and B versus C. Groups A and B and spontaneous preterm labor (SPL) independently predicted high Lactobacillus counts on day 28; groups A, B, and C and SPL predicted high Bifidobacterium counts. CONCLUSION: Proportion of infants colonized with probiotic species was similar with high-dose and standard dose regimes.

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 low-birth-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. CONCLUSION: Very low birth weight infants admitted in neonatal intensive care units have abnormal intestinal colonization patterns.

Longitudinal growth of very low birth weight neonates during first year of life and risk factors for malnutrition in a developing country.

AIMS: To study growth of very low birth weight neonates (VLBW) during first year and identify risk factors for malnutrition. METHODS: Neonates ≤34 weeks and ≤1500 g enrolled in a human milk fortification trial were prospectively followed till 1 year corrected age (CA). Anthropometry was plotted on WHO charts. Risk factors were compared between well nourished and underweight infants. RESULTS: One hundred and thirty-two, 127, 110, 99 and 101 neonates were followed at CA of 40 weeks, 3, 6, 9 and 12 months. Weight (Mean Z score -2.3 ± 1.2 to -1.7 ± 1.4; p = 0.005) and length (-2.1 ± 1.5 to -1.5 ± 1.3; p = 0.004) improved significantly, from 40 weeks to one year while head circumference declined (-0.92 ± 1.1 to -1.2 ± 1.1; p < 0.001). Incidence of underweight, stunting, microcephaly and wasting changed from 63%, 53%, 13% and 52% neonates at 40 weeks to 41%, 32%, 21% and 27% at one year. Growth between fortified and unfortified or small for gestational age (SGA) and appropriate for gestational age (AGA) groups were similar, while extremely low birth weight (ELBW) neonates showed poorer growth. Z score of weight at 3 months emerged as an independent predictor of malnutrition at one year. CONCLUSION: VLBW neonates, especially the ELBW group remained growth retarded at CA of one year. Z score of weight at 3 months was a significant risk factor for malnutrition at one year.

Feed intolerance and necrotizing enterocolitis in preterm small-for-gestational age neonates with normal umbilical artery Doppler flow.

This was a prospective observational study conducted in a level III neonatal unit in North India to measure the incidence of feed intolerance and necrotizing enterocolitis (NEC) in preterm small for gestational age (SGA) neonates with normal umbilical artery Doppler flow in comparison with gestation matched appropriate for gestational age (AGA) neonates. Fifty consecutive singleton SGA preterms between 28 and 34 weeks gestation with normal Doppler were enrolled and 50 gestation matched AGA served as controls. There was a trend toward more feed intolerance (22% vs. 12%, p = 0.183), NEC (12% vs. 6%, p = 0.295) and mortality (8% vs. 2%, p = 0.362) in SGA group and these babies also had significantly more hypoglycemia (p = 0.000) and polycythemia (p = 0.032) and longer hospital stay (p = 0.017).

Postnatal percentile growth charts for Indian appropriate for gestational age (AGA) very low birth weight babies.

AIMS: To develop postnatal percentile growth charts for Indian very low birth weight (VLBW) appropriate for gestational age (AGA) babies till 37 weeks post conceptional age (PCA). METHODS: Prospective, mixed longitudinal study in 105 VLBW AGA (male 73 and female 32) babies weighing <1500 g and <34 weeks gestation born over 1 year. All were weighed daily until discharge and then weekly till 37 weeks of PCA. The percentile weight curves were computed in four categories : ≤28 weeks, 29-30, 31-32 and 33 weeks, and a total of seven percentile distributions (3rd, 10th, 25th, 50th, 75th, 90th& 97th) were generated. Entire data were subjected to Tanner's 1951 method to compute mean and standard deviation for body weight. The arithmetic mean served the 50(th) percentile. RESULTS: All babies at birth were <50th centile as per Lubchenco's intrauterine growth chart. This pattern was more evident in higher gestation (31-32 and 33 weeks) than lower gestation (≤28 and 29-30 weeks). At 37 weeks PCA, all were <10th centile and the lowest was in ≤28 weeks gestation. CONCLUSIONS: Our babies are born smaller, and growth rate is slower than their western counterparts. Babies at lowest gestation had slowest postnatal growth. Hence, we need a separate growth chart for our babies.

Iron status at birth and at 4 weeks in preterm-SGA infants in comparison with preterm and term-AGA infants.

OBJECTIVE: To determine the iron status at birth in preterm small for gestational age (SGA) in comparison with preterm appropriate for gestation (AGA) and term-AGA infants. METHODS: Mother-infant pairs with gestation of < 37 weeks, both SGA, and preterm-AGA and term-AGA as control were enrolled. Maternal, cord blood and infant blood samples at 4 weeks were obtained for various iron indices - cord serum ferritin, proportion of infants with "low" serum ferritin, serum ferritin at 4 weeks and correlation among maternal and neonatal iron indices - hemoglobin,serum ferritin and total iron-binding capacity. RESULTS: There were 50 mother-infant pairs in each group. Cord serum ferritin levels were less in preterm-SGA group as compared to preterm-AGA group (median [interquartile range]: 68 [30 113] vs. 120 [73 127], p = 0.002) and preterm-AGA had less cord ferritin than term-AGA (141 [63 259], p = 0.006). The proportion of the infants with "low" serum ferritin was more in preterm-SGA than in preterm-AGA (16 [32%] vs. 5 [10%], p = 0.01). The serum ferritin levels at follow-up were also less in preterm-SGA as compared to preterm-AGA (143.5 ± 101 vs. 235.1 ± 160, p = 0.004). Other cord blood iron indices and follow-up serum ferritin levels were similar. There was no correlation among various maternal and neonatal cord iron parameters. CONCLUSIONS: Preterm-SGA infants have lesser total iron stores as compared to gestation-matched AGA infants, which is again lesser than term infants. Future studies can be planned to look at iron status at 12 months as well as their neurodevelopmental outcome.

Iron status at birth and at 4 weeks in term small-for-gestation infants in comparison with appropriate-for-gestation infants.

OBJECTIVE: To determine body iron stores at birth in term small-for-gestational age (SGA) infants as compared to appropriate-for-gestational age (AGA) infants. METHODS: In this prospective study, mother-infant pairs with gestation of  ≥ 37 weeks and birth weight of at least 1.5 kg were enrolled. Asymmetric SGA infants were taken as cases and term AGA infants as controls. Maternal, cord blood, and infant blood samples at 4 weeks were obtained for measurement of various iron indices - cord serum ferritin, serum ferritin at 4 weeks, and correlation among maternal and neonatal iron indices - Hb, serum iron, ferritin, and total iron binding capacity (TIBC). RESULTS: There were 50 SGA and 50 AGA mother-infant pairs. Cord serum ferritin levels were low in SGA group as compared to AGA [median (IQR): 68 (30,136) vs. 141 (63,259), p = 0.007]. The proportion of infants with 'low' cord ferritin (< 40 µg/l) were more in SGA [p = 0.05]. There was no correlation among various maternal and neonatal cord iron parameters. The serum ferritin levels at 4 weeks were similar in both the groups (p = 0.16). CONCLUSIONS: Term SGA infants have lesser total iron stores as compared to AGA infants at birth. Future studies can be designed to look at long-term neurodevelopmental outcome of the SGA babies with low as well as normal ferritin and also the role of early iron supplementation in term SGA neonates.

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.

Natural history and predictive risk factors of prolonged unconjugated jaundice in the newborn.

BACKGROUND: This study aimed to investigate the natural course and risk factors for prolonged unconjugated jaundice (PUJ) in neonates. METHODS: This was a prospective descriptive study conducted in a tertiary care referral hospital of Northern India. The study included neonates who presented with clinical jaundice beyond 14 days of age. A detailed history, clinical examination and investigations were performed in all. All were followed till the normalization of clinical jaundice or up to 8 weeks of age, whichever was earlier. The key outcome measure was time to normalization of PUJ. Predictive risk factors for PUJ were analyzed by comparing with matched controls. Regression analysis was done for independent predictive risk factors of PUJ. RESULTS: A total of 71 infants presented with prolonged jaundice (PJ). Out of these, 66 infants (93%) had PUJ. Glucose-6-phosphate dehydrogenase (G6PD) deficiency was the most commonly identified association of PUJ (24%). The median duration of jaundice in infants with PUJ was 5 weeks (range: 5-8). PJ in siblings (OR 2.9 [1.1-7.6]), oxytocin use during labor (OR 3.4 [1.1-10.4]) and G6PD deficiency (OR 4.0 [1.1-14.1]) were independent predictors of PUJ. CONCLUSIONS: Irrespective of the etiology, by 8 weeks, PUJ disappeared in all infants. G6PD deficiency was the most common association of PUJ. A history of PJ in siblings, use of oxytocin during labor and G6PD deficiency were independent predictors for PUJ.

Galactose specific adhesin of enteroaggregative E. coli induces IL-8 secretion via activation of MAPK and STAT-3 in INT-407 cells.

BACKGROUND: Enteroaggregative Escherichia coli (EAEC) is one of the most common bacterial pathogens associated with the etiology of persistent diarrhea. A characteristic feature of EAEC-pathogenesis is the induction of profound inflammatory response in the intestinal epithelium. The present study was designed to investigate the underlying mechanism of inflammatory responses induced by a novel galactose specific adhesin of T7 strain of EAEC (EAEC-T7) in human intestinal epithelial cell line (INT-407). METHODS: INT-407 cells were stimulated with the adhesin in the absence and presence of anti-adhesin (IgG(AD))/d-galactose/H7/staurosporin (inhibitor of PKC)/PD098059 (inhibitor of MEK)/SB203580 (inhibitor of p38-MAPkinase)/AG490 (inhibitor of JAK (-2,-3)/STAT-3 pathway). The expression of activated Raf-1, MEK-1, ERK1/2, JNK, p38-MAPK and STAT-3 was analyzed by Western immunoblot. Release of interleukin-8 (IL-8) was measured by ELISA. RESULTS: The adhesin was found to induce activation of Raf-1, MEK-1, ERK1/2, p38-MAPK and STAT-3, which was reduced in the presence of IgG(AD)/d-galactose. The activation of Raf-1 was found to be attenuated in the presence of H7/staurosporin. The expression of phosphorylated STAT-3 was downregulated in the presence of AG490 and PD098059. Further, the adhesin induced IL-8 secretion was reduced in the presence of the inhibitors of MEK (PD098059), p38-MAPK (SB203580) and JAK (-2,-3)/STAT-3 pathway (AG490). CONCLUSIONS: We propose that STAT-3 activation is quintessential for the galactose specific adhesin induced IL-8 secretion by INT-407 cells and must occur in concert with the activation of ERK1/2. GENERAL SIGNIFICANCE: Our contribution regarding the galactose specific adhesin mediated signaling leads to an improved understanding of the EAEC-pathogenesis and may provide novel therapeutic approaches to combat EAEC infection.

Neurodevelopmental outcome of acute bilirubin encephalopathy.

The aim of the study was to determine the neurodevelopmental outcome of acute bilirubin encephalopathy (ABE) in children who underwent double volume exchange transfusion (DVET). The 25 referred newborns of ≥ 35 weeks gestation with total serum bilirubin >20 mg dl(-1) and signs of ABE were enrolled and followed up at 3, 6, 9 and 12 months. Denver Development Screening Test (DDST), Neurological examination along with MRI at discharge and brain stem evoked response audiometry (BERA) at 3 months were done. Abnormal neurodevelopment was defined as either (i) cerebral palsy or (ii) abnormal DDST or (iii) abnormal BERA. The mean bilirubin at admission was 37 mg dl(-1). MRI and BERA were abnormal in 61% and 76%. At 1 year, DDST and neurological abnormality were seen in 60% and 27% and 80% had combined abnormal neurodevelopment. MRI had no relation (P = 0.183) but abnormal BERA had a significant association (P = 0.004) with abnormal outcome. Intermediate and advanced stages of ABE associated with significant adverse outcome in spite of DVET.

Effect of delay in analysis on neonatal cerebrospinal fluid parameters.

OBJECTIVES: The effect of delayed analysis on cerebrospinal fluid (CSF) white blood cell (WBC) count and glucose has never been studied in neonates. DESIGN: Prospective cohort study. SETTING: Level III newborn unit. PATIENTS: Neonates undergoing lumbar puncture were enrolled after consent. CSF was analysed at baseline (30 minutes) for protein, WBC and glucose; and from the same sample for WBC and glucose after a lag of 2 h and 4 h after lumbar puncture. Those with traumatic/inadequate CSF were excluded. Subjects were classified in three groups (n = 20 each) based on baseline WBC count: no WBC, 1-30 WBC and >30 WBC/microl. Analysis was by repeated-measures ANOVA. RESULTS: There was a significant decline in mean (SD) CSF glucose from baseline to 2 h and 4 h (41.0 (19) to 38.3 (19) and 36.2 (20) mg/dl, respectively) and WBC count (36 (45) to 28.6 (38) and 23.8 (34) cells/microl, respectively; both p<0.001). CSF glucose and WBC declined in all three groups (p<0.001). High baseline CSF WBC (p<0.001) and protein (p<0.001) was associated with a more rapid decline in the levels of CSF WBC, but not glucose. True CSF parameters could be predicted from 4-h parameters: "baseline glucose 5.4 + 0.98 (4-h glucose)" (adjusted R(2) 97.2%, p<0.001) and "baseline WBC 1.3 (4-h WBC) +0.05 (protein)" (adjusted R(2) 98.8%, p<0.001). In group 3, a diagnosis of meningitis (based on pleocytosis) would be missed in 52.6% and 78.9% subjects at 2 h and 4 h, respectively. CONCLUSIONS: CSF WBC count and glucose decrease significantly with time. Reliance on WBC counts of delayed samples can result in underdiagnosis.

Baseline illness severity does not alter accuracy of neonatal sepsis screen.

We investigated the relationship between illness severity and accuracy of neonatal sepsis screen. Consecutive neonates with clinically suspected early onset sepsis (EOS) were enrolled and blood culture and sepsis screen [C-reactive protein, absolute neutrophil count, immature to total ratio (ITR) and microerythrocyte sedimentation rate] were performed. Exclusion criteria were prior antibiotic exposure, nonavailable reports, and contaminated cultures. Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE-II) was used to categorize neonates into "mild to moderate" (score 40) illness. Sepsis was defined as positive blood culture, and positive screen as >or=2 parameters positive. Of 125 subjects, 86 had mild to moderate and 39, severe illness. Twenty-eight (22%) subjects had sepsis. Sensitivity, specificity, negative predictive value, positive predictive value, likelihood ratio of positive test, and likelihood ratio of negative test of the sepsis screen and screen parameters were similar between the two groups. The sensitivity of the screen was 37.5% and 25% for mild to moderate illness and severe illness, respectively. Only ITR values correlated with SNAPPE-II scores in patients with "sepsis" (rho 0.4; P = 0.036). The severity of underlying illness does not alter the performance of the sepsis screen in diagnosing culture-positive EOS.

Intrapartum antibiotics and risk factors for early onset sepsis.

OBJECTIVE: To determine the independent risk factors for early onset neonatal sepsis (EONS) in a setting where the policy is to use intrapartum antibiotic prophylaxis (IAP) for known risk factors. DESIGN: Prospective cohort study. SETTING: Level III neonatal unit in a developing country. PATIENTS: Consecutive mother-infant dyads (gestation < or =34 weeks) with no major neonatal malformations. INTERVENTIONS: Thirteen putative maternal and neonatal risk factors and use of IAP were assessed. Neonates were followed until 72 h of life for signs of EONS. Blood cultures were drawn on clinical suspicion of EONS and/or prior to starting prophylactic antibiotics for high risk asymptomatic neonates. MAIN OUTCOME: Culture-proven EONS (onset at <72 h). RESULTS: 601 mother-infant dyads were enrolled (mean (SD) gestation=31.8 (2) weeks; mean (SD) birth weight 1559.4 (452) g). The best fitted multivariable logistic regression model had six independent risk factors (adjusted OR (95% CI)): vaginal examinations > or =3 (9.5 (3 to 31)), clinical chorioamnionitis (8.8 (2 to 43)), birth weight <1500 g (2.8 (2 to 5)), male sex (2.7 (2 to 5)), gestation <30 weeks (2 (1 to 4)) and no IAP (2 (1.04 to 4)). Regression coefficients were converted into scores of 6, 6, 3, 3, 2 and 2, respectively. Internal prediction accuracy was 86.5% and c statistic was 0.75 (95% CI 0.70 to 0.81, p<0.001). CONCLUSIONS: Vaginal examinations > or =3, clinical chorioamnionitis, birth weight <1500 g, male sex, gestation <30 weeks and no intrapartum antibiotics were independent risk factors for EONS among preterm infants of < or =34 weeks' gestation.