Modified Kramer's versus Kramer's Method for Clinical Assessment of Jaundice in Term and Near-Term Neonates.

OBJECTIVES: To compare the performance of Modified Kramer's and Kramer's methods in terms of agreement with total serum bilirubin (TSB). METHODS: This cross-sectional study was done in Level-III neonatal unit in New Delhi. Visibly jaundiced neonates born at ≥35 wk of gestation were enrolled and examined by (i) conventional Kramer's, (ii) Modified Kramer's in artificial (MK-A) and (iii) natural daylight (MK-N), and finally sampled for estimation of TSB by point-of-care spectrophotometry. The primary outcomes were agreement of Kramer's and Modified Kramer's with TSB and accuracy in terms of proportion of bilirubin estimates lying within ±2 mg/dL of TSB; secondary outcome was agreement of MK-A and MK-N with TSB. RESULTS: A total of 144 neonates with median gestation of 37 wk and mean birth weight of 2788 g were enrolled. Bland Altman analysis between Kramer's and TSB yielded mean difference of 1.7 mg/dL, 95% limits of agreement (LOA) -3.1 to 6.6 mg/dL. For Modified Kramer's and TSB, mean difference was -0.02 mg/dL, 95% LOA -4.7 to 4.7 mg/dL under artificial light; 0.02 mg/dL, 95% LOA -4.2 to 4.2 mg/dL under natural daylight. MK-N had highest proportion of bilirubin estimates lying within ±2 mg/dL of TSB (68.7%) as compared to MK-A (59.7%) [OR, 1.77; 95% CI, 1.09 to 2.86] and Kramer's (45.8%) [OR, 1.65; 95% CI, 1.27 to 2.15]. CONCLUSIONS: Though all the three methods had poor agreement with TSB, Modified Kramer's method when performed in natural light had reasonable accuracy, however limited clinical utility, in evaluation of clinical jaundice.

Stepwise interventions for improving hand hygiene compliance in a level 3 academic neonatal intensive care unit in north India.

OBJECTIVE: We evaluated effect of sequentially introducing four WHO-recommended interventions to promote hand-hygiene compliance in tertiary-care NICU. STUDY DESIGN: Four dedicated research nurses directly observed doctors and nurses to record success in hand-hygiene opportunities at randomly selected NICU beds and randomly sampled time-slots in four phases (of 4-weeks each): I-Baseline, II-Self-directed learning; III-Participatory learning; IV-Closed-Circuit Television (CCTV); and V-CCTV-plus (with feedback). FINDINGS: Hand-hygiene compliance changed from 61.8% (baseline) to 77% (end) with overall relative change: 24.6% (95% CI 18, 32; p value= 0.003); compared with preceding phase, relative changes of 21% (15, 28; <0.001), 4% (0, 8; 0.008), -10% (-13, -6; <0.001), and 10% (5, 15; <0.001) during phases II, III, IV, and V, respectively were observed. Rise in hand-hygiene compliance was higher for after-WHO-moments (12.7%; upto 2.5-folds for moment 5, <0.001) compared to before-WHO-moments (5.2%). Educational interventions, feedback and monitoring WHO moments can improve hand-hygiene compliance significantly among health-care providers in NICU.

Reliability of transcutaneous bilirubinometry from shielded skin in neonates receiving phototherapy: a prospective cohort study.

OBJECTIVE: To determine the agreement between transcutaneous bilirubin (TcB) measured from shielded skin and serum total bilirubin (STB) in infants (34 to 41 weeks of gestation) with hyperbilirubinemia receiving phototherapy (PT). STUDY DESIGN: In this prospective cohort study, we shielded a small area of skin on sternum using a commercial photo-opaque patch (BilEclipseTM, Philips Respironics, Murrysville, PA, USA). The TcB from the shielded skin (TcBs) and STB were measured at four time points-before initiation, 12 and 24 h during and once after (12 h) cessation of PT. TcB was measured using multiwavelength transcutaneous bilirubinometer (BiliChek, Philips Children's Medical Ventures, Monroeville, PA, USA). The STB was measured in triplicate by spectrophotometry (Apel BR 5100, APEL, Japan). Bland and Altman plots were drawn to determine agreement between the TcBs and STB. RESULTS: The gestation and birth weight of enrolled neonates were 37.0 (1.0) weeks and 2750 (458) g, respectively. The age at initiation and duration of PT were 75 (27 to 312) and 25.3 (4.4) h, respectively. Bland and Altman plot showed poor agreement between TcBs and STB at all time points. The gradient (median, range) between TcBs and STB at 0, 12, 24 h and 12 h after cessation of PT were -0.2 (-4.9 to 3.5), 1.4 (-4.7 to 4.0), 1.5 (-3.8 to 9.4) and 2 (-2.9 to 5.8) mg dl-1. The proportions of TcBs values outside ±1.5 mg dl-1 of STB ranged from 47 to 64% at four time points. CONCLUSION: TcBs does not appear to be reliable for estimating serum bilirubin in late preterm and term neonates receiving PT.

State of newborn health in India.

About 0.75 million neonates die every year in India, the highest for any country in the world. The neonatal mortality rate (NMR) declined from 52 per 1000 live births in 1990 to 28 per 1000 live births in 2013, but the rate of decline has been slow and lags behind that of infant and under-five child mortality rates. The slower decline has led to increasing contribution of neonatal mortality to infant and under-five mortality. Among neonatal deaths, the rate of decline in early neonatal mortality rate (ENMR) is much lower than that of late NMR. The high level and slow decline in early NMR are also reflected in a high and stagnant perinatal mortality rate. The rate of decline in NMR, and to an extent ENMR, has accelerated with the introduction of National Rural Health Mission in mid-2005. Almost all states have witnessed this phenomenon, but there is still a huge disparity in NMR between and even within the states. The disparity is further compounded by rural-urban, poor-rich and gender differentials. There is an interplay of different demographic, educational, socioeconomic, biological and care-seeking factors, which are responsible for the differentials and the high burden of neonatal mortality. Addressing inequity in India is an important cross-cutting action that will reduce newborn mortality.

When do newborns die? A systematic review of timing of overall and cause-specific neonatal deaths in developing countries.

About 99% of neonatal deaths occur in low- and middle-income countries. There is a paucity of information on the exact timing of neonatal deaths in these settings. The objective of this review was to determine the timing of overall and cause-specific neonatal deaths in developing country settings. We searched MEDLINE via PubMed, Cochrane CENTRAL, WHOLIS and CABI using sensitive search strategies. Searches were limited to studies involving humans published in the last 10 years. A total of 22 studies were included in the review. Pooled results indicate that about 62% of the total neonatal deaths occurred during the first 3 days of life; the first day alone accounted for two-thirds. Almost all asphyxia-related and the majority of prematurity- and malformation-related deaths occurred in the first week of life (98%, 83% and 78%, respectively). Only one-half of sepsis-related deaths occurred in the first week while one-quarter occurred in each of the second and third to fourth weeks of life. The distribution of both overall and cause-specific mortality did not differ greatly between Asia and Africa. The first 3 days after birth account for about 30% of under-five child deaths. The first week of life accounts for most of asphyxia-, prematurity- and malformation-related mortality and one-half of sepsis-related deaths.

Umbilical cord cleansing with chlorhexidine in neonates: a systematic review.

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of chlorhexidine application to the umbilical cord in neonates. We searched MEDLINE and other electronic databases, and included all RCTs that evaluated the effect of single or multiple chlorhexidine cord applications on the neonatal mortality rate (NMR) and/or the incidence of systemic sepsis and omphalitis. A total of six RCTs-four community-based cluster RCTs and two hospital-based trials-were included in the review. Of the four cluster RCTs, three were conducted in South Asia in settings with high rates of home births (>92%) while the fourth, available only as an abstract, was conducted in Africa. Pooled analysis by the 'intention-to-treat' principle showed a significant reduction in NMR after chlorhexidine application (four studies; relative risk (RR) 0.85; 95% confidence interval (CI) 0.76 to 0.95; fixed effects (FE) model). On subgroup analysis, only multiple applications showed a significant effect (four studies; RR 0.88; 95% CI 0.78 to 0.99) whereas a single application did not (one study; RR 0.86; 0.73 to 1.02). Similarly, only the community-based trials showed a significant reduction in NMR (three studies; RR 0.86; 95% CI 0.77 to 0.95), while the hospital-based study did not find any effect (RR 0.11; 0.01 to 2.03). Since all the studies were conducted in high-NMR settings (⩾30 per 1000 live births), we could not determine the effect in settings with low NMRs. Only one study-a hospital-based trial from India-reported the incidence of neonatal sepsis; it did not find a significant reduction in any sepsis (RR 0.67; 95% CI 0.35 to 1.28). Pooled analysis of community-based studies revealed significant reduction in the risk of omphalitis in infants who received the intervention (four studies; RR 0.71; 95% CI 0.62 to 0.81). The hospital-based trial had no instances of omphalitis in either of the two groups. Chlorhexidine application delayed the time to cord separation (four studies; mean difference 2.11 days; 95% CI 2.07 to 2.15; FE model). Chlorhexidine application to the cord reduces the risk of neonatal mortality and omphalitis in infants born at home in high-NMR settings. Routine chlorhexidine application, preferably daily for 7 to 10 days after birth, should therefore be recommended in these infants. Given the paucity of evidence, there is presently no justification for recommending this intervention in infants born in health facilities and/or low-NMR settings.

Efficacy and safety of CPAP in low- and middle-income countries.

We conducted a systematic review to evaluate the (1) feasibility and efficacy and (2) safety and cost effectiveness of continuous positive airway pressure (CPAP) therapy in low- and middle-income countries (LMIC). We searched the following electronic bibliographic databases-MEDLINE, Cochrane CENTRAL, CINAHL, EMBASE and WHOLIS-up to December 2014 and included all studies that enrolled neonates requiring CPAP therapy for any indication. We did not find any randomized trials from LMICs that have evaluated the efficacy of CPAP therapy. Pooled analysis of four observational studies showed 66% reduction in in-hospital mortality following CPAP in preterm neonates (odds ratio 0.34, 95% confidence interval (CI) 0.14 to 0.82). One study reported 50% reduction in the need for mechanical ventilation following the introduction of bubble CPAP (relative risk 0.5, 95% CI 0.37 to 0.66). The proportion of neonates who failed CPAP and required mechanical ventilation varied from 20 to 40% (eight studies). The incidence of air leaks varied from 0 to 7.2% (nine studies). One study reported a significant reduction in the cost of surfactant usage with the introduction of CPAP. Available evidence suggests that CPAP is a safe and effective mode of therapy in preterm neonates with respiratory distress in LMICs. It reduces the in-hospital mortality and the need for ventilation thereby minimizing the need for up-transfer to a referral hospital. But given the overall paucity of studies and the low quality evidence underscores the need for large high-quality studies on the safety, efficacy and cost effectiveness of CPAP therapy in these settings.

Vitamin K prophylaxis for prevention of vitamin K deficiency bleeding: a systematic review.

We conducted a systematic review to evaluate the burden of late vitamin K deficiency bleeding (VKDB) and the effect of vitamin K prophylaxis on the incidence of VKDB. We searched MEDLINE and other electronic databases, and included all observational studies including population surveys as well as randomized controlled trials (RCT). The median (interquartile range) burden of late VKDB was 35 (10.5 to 80) per 100 000 live births in infants who had not received prophylaxis at birth; the burden was much higher in low- and middle-income countries as compared with high-income countries-80 (72 to 80) vs 8.8 (5.8 to 17.8) per 100 000 live births. Two randomized trials evaluated the effect of intramuscular (IM) prophylaxis on the risk of classical VKDB. Although one trial reported a significant reduction in the incidence of any bleeding (relative risk (RR) 0.73, 95% confidence interval (CI) 0.56 to 0.96) and moderate to severe bleeding (RR 0.19, 0.08 to 0.46; number needed to treat (NNT) 74, 47 to 177), the other trial demonstrated a significant reduction in the risk of secondary bleeding after circumcision in male neonates (RR 0.18, CI 0.08 to 0.42; NNT 9, 6 to 15). No RCTs evaluated the effect of vitamin K prophylaxis on late VKDB. Data from four surveillance studies indicate that the use of IM/subcutaneous vitamin K prophylaxis could significantly reduce the risk of late VKDB when compared with no prophylaxis (pooled RR 0.02; 95% CI 0.00 to 0.10). When compared with IM prophylaxis, a single oral dose of vitamin K increased the risk of VKDB (RR 24.5; 95% CI 7.4 to 81.0) but multiple oral doses did not (RR 3.64; CI 0.82 to 16.3). There is low-quality evidence from observational studies that routine IM administration of 1 mg of vitamin K at birth reduces the incidence of late VKDB during infancy. Given the high risk of mortality and morbidity in infants with late VKDB, it seems appropriate to administer IM vitamin K prophylaxis to all neonates at birth. Future studies should compare the efficacy and safety of multiple oral doses with IM vitamin K and also evaluate the optimal dose of vitamin K in preterm neonates.

Efficacy and safety of surfactant replacement therapy for preterm neonates with respiratory distress syndrome in low- and middle-income countries: a systematic review.

Surfactant replacement therapy (SRT) has been shown to reduce mortality and air leaks in preterm neonates from high-income countries (HICs). The safety and efficacy of SRT in low- and middle- income countries (LMICs) have not been systematically evaluated. The major objectives of this review were to assess the (1) efficacy and safety, and (2) feasibility and cost effectiveness of SRT in LMIC settings. We searched the following databases-MEDLINE, CENTRAL, CINAHL, EMBASE and WHOLIS using the search terms 'surfactant' OR 'pulmonary surfactant'. Both experimental and observational studies that enrolled preterm neonates with or at-risk of respiratory distress syndrome (RDS) and required surfactant (animal-derived or synthetic) were included. A total of 38 relevant studies were found; almost all were from level-3 neonatal units. Pooled analysis of two randomized controlled trials (RCTs) and 22 observational studies showed a significant reduction in mortality at the last available time point in neonates who received SRT (relative risk (RR) 0.67; 95% confidence interval (CI) 0.57 to 0.79). There was also a significant reduction in the risk of air leaks (five studies; RR 0.51; 0.29 to 0.90). One RCT and twelve observational studies reported the risk of bronchopulmonary dysplasia (BPD) with contrasting results; while the RCT and most before-after/cohort studies showed a significant reduction or no effect, the majority of the case-control studies demonstrated significantly higher odds of receiving SRT in neonates who developed BPD. Two studies-one RCT and one observational-found no difference in the proportion of neonates developing pulmonary hemorrhage, while another observational study reported a higher incidence in those receiving SRT. The failure rate of the intubate-surfactant-extubate (InSurE) technique requiring mechanical ventilation or referral varied from 34 to 45% in four case-series. No study reported on the cost effectiveness of SRT. Available evidence suggests that SRT is effective, safe and feasible in level-3 neonatal units and has the potential to reduce neonatal mortality and air leaks in low-resource settings as well. However, there is a need to generate more evidence on the cost effectiveness of SRT and its effect on BPD in LMIC settings.

Surfactant therapy and antibiotics in neonates with meconium aspiration syndrome: a systematic review and meta-analysis.

Meconium aspiration syndrome (MAS), a common cause of respiratory failure in neonates, is associated with high mortality and morbidity. The objectives of this review were to evaluate the effects of administration of (a) surfactant-either as lung lavage (SLL) or bolus surfactant (BS) and (b) antibiotics on mortality and severe morbidities in neonates with MAS. We searched the following databases: MEDLINE via PubMed, Cochrane CENTRAL, WHOLIS and CABI using sensitive search strategies. We included eight studies on use of surfactant and three studies on use of antibiotics. Neither SLL nor BS reduced the risk of mortality in neonates with MAS (relative risk (RR) 0.38, 95% confidence interval (CI) 0.09 to 1.57; and RR 0.80, 95% CI 0.39 to 1.66, respectively). Both SLL and BS reduced the duration of hospital stay (mean difference -2.0, 95% CI -3.66 to -0.34; and RR -4.68, 95% CI -7.11 to -2.24 days, respectively) and duration of mechanical ventilation (mean difference -1.31, 95% CI -1.91 to -0.72; and mean difference 5.4, 95% CI -9.76 to -1.03 days). Neonates who received BS needed extracorporeal membrane oxygenation (ECMO) less often than the controls (RR 0.64, 95% CI 0.46 to 0.91). Use of antibiotics for MAS did not result in significant reduction in the risk of mortality, sepsis or duration of hospital stay. Surfactant administration either as SLL or BS for MAS was found to reduce the duration of mechanical ventilation and hospital stay; BS also reduced the need for ECMO. Administration of antibiotics did not show any significant clinical benefits in neonates with MAS and no evidence of sepsis. Given the limited number of studies and small number of neonates enrolled, there is an urgent need to generate more evidence on the efficacy and cost-effectiveness of these two treatment modalities before recommending them in routine clinical practice.

Effect of position of infant during phototherapy in management of hyperbilirubinemia in late preterm and term neonates: a randomized controlled trial.

OBJECTIVE: To evaluate the effect of supine position when compared with periodic change of position during phototherapy in late preterm and term neonates (35 to 42 weeks) with hyperbilirubinemia on the duration of phototherapy. STUDY DESIGN: We randomly allocated enrolled neonates with hyperbilirubinemia to either no change in position (supine group (SG); n=54) or two-hourly change of position from supine to prone and vice versa (turning group (TG); n=46). All the infants received single surface phototherapy by two dedicated compact fluorescent light units. Total serum bilirubin (TSB) was measured at the start of phototherapy and then every 12 ± 2 h until the end of phototherapy. Phototherapy was stopped when two values were below the cut-off for age and gestational age as per the American Academy of Pediatrics Subcommittee on Hyperbilirubinemia guidelines nomogram for the management of hyperbilirubinemia in infants >35 weeks of gestation. The primary outcome was duration of phototherapy and secondary outcome was rate of fall of bilirubin within the first 24 ± 2 h after the initiation of phototherapy. RESULT: Baseline characteristics including birth weight (g, 2752 ± 478 vs 2748 ± 416 P=0.96), gestation (week, 37.1 ± 1.2 vs 37.4 ± 1.3, P=0.26) were similar in the two groups. There was no difference in the duration of phototherapy between the SG (mean ± s.d., hour, 25.5 ± 8) and TG (mean ± s.d., hour, 24.8 ± 5), mean difference (95% confidence interval), hour, 0.7 (-2.03, 3.44, P=0.6). Rate of fall of bilirubin was also similar in both supine and turning groups with mean difference of -0.020 (95% confidence interval: -0.061, 0.021, P=0.34). CONCLUSION: Nursing babies in supine position when compared with periodic position change during phototherapy does not decrease the duration of phototherapy.

Does skin cleansing with chlorhexidine affect skin condition, temperature and colonization in hospitalized preterm low birth weight infants?: a randomized clinical trial.

OBJECTIVE: To examine if single skin cleansing with 0.25% chlorhexidine affects skin condition, temperature and bacterial colonization in stable preterm (28-36 weeks gestational age) low birth weight (1001-2000 g) infants admitted in a health facility. METHODS: Eligible infants were randomized within 3 h of birth into the following three groups: chlorhexidine, normal saline or no skin cleansing. Infants in the first two groups were wiped once with baby wipes containing either 0.25% chlorhexidine or saline. Skin condition, axillary temperature and skin colonization rates in the axilla and the groin were assessed at specified time intervals after intervention. RESULTS: In all, 60 infants were included in the study (20 in each group). Median skin condition scores at 72 and 168 h after the intervention were 2 and 2, respectively, in all three groups. At 30 min after skin cleansing, two infants each in the chlorhexidine and saline cleansing groups and none in the no cleansing group experienced cold stress (36-36.4 degrees C). There was, however, no difference in mean skin temperature of the groups (36.6 degrees C). At 24 h, skin colonization rates in the axilla were 22.2, 52.7, and 57.9%, respectively, in the chlorhexidine, saline and no cleansing groups (P=0.06); skin cleansing with chlorhexidine reduced the incidence of colonization by 62% compared with no cleansing (relative risk (RR): 0.38, 95% confidence interval (CI): 0.15, 0.98), but there was no significant reduction when compared with saline cleansing (RR: 0.42; 0.16-1.10). Axillary colonization rates at 72 h and colonization at the groin at 24 and 72 h were not significantly different across the three groups. CONCLUSION: Single skin cleansing with 0.25% chlorhexidine did not adversely affect skin condition or temperature in hospitalized preterm infants and reduced axillary-skin colonization at 24 h after the intervention. Trials are needed to evaluate the efficacy of such an intervention on the incidence of infections in preterm neonates.