Fetal vascular malperfusion (FVM): diagnostic implications and clinical associations.

INTRODUCTION: Fetal vascular malperfusion (FVM) is diagnosed by the presence of vascular lesions in the muscularized fetal vessels in the placenta and the resultant changes in the downstream villi. The Amsterdam Placental Working Group recognizes two patterns of FVM namely segmental and global. The aim of this study was to estimate the frequency of FVM lesion in our population and to understand its neonatal associations. METHODS: Fifty-four placentas with FVM and 56 controls collected over 34 months. The maternal and neonatal details were collected from the case charts. The patterns and grades of FVM lesions were related to the clinical factors and significance analyzed statistically using the Chi-square test and t-test and p < .05 was considered significant. RESULTS: The frequency of FVM was 8.7%. The FVM group showed lower mean gestational age, birth weight, and placental weight with a higher frequency of IUGR. Poor neonatal survival, non-reassuring fetal status, neurological abnormalities, neonatal sepsis, asphyxia, low Apgar, and respiratory support requirement were significantly higher in the FVM group. A similar frequency of segmental and global lesions was seen. High grade lesions (n = 35) were common than low grade (n = 19). Neonatal associations were more often seen in segmental and high-grade lesions. DISCUSSION: In the absence of antenatal diagnostic tools to identify FVM, placental examination is critical and the only definitive method to diagnose FVM, which alerts the clinician to monitor for several neonatal morbidities. Identification and typing the lesion as per the new guidelines proves significant risk associations with specific types of FVM.

Comparison of efficacy of a 7-day versus a 14-day course of intravenous antibiotics in the treatment of uncomplicated neonatal bacterial sepsis: study protocol of a randomized controlled non-inferiority trial.

BACKGROUND: Neonatal sepsis is a global public health problem. There is no consensus regarding the optimum duration of antibiotics for culture-proven neonatal sepsis. Published randomized controlled trials (RCTs) comparing shorter versus longer courses of antibiotics provide low-quality evidence with serious risk of bias. We hypothesized that among neonates with uncomplicated culture-proven sepsis, antibiotic duration of 7 days is not inferior to 14 days. METHODS: This is a multi-centric, parallel-group, stratified, block-randomized, active-controlled, non-inferiority trial with outcome assessment blinded. Stratification is by center and birth weight. Neonates weighing ≥1000 g at birth, with blood-culture-proven sepsis (barring Staphylococcus aureus and fungi), without conditions warranting > 14 days antibiotics, and who clinically remit, are enrolled in the RCT on day 7 of administration of sensitive antibiotics. They are randomly allocated to no further antibiotics (intervention arm: total 7 days) or 7 more days of the same antibiotics (control arm: total 14 days). Allocation is concealed by opaque, sealed envelopes. The primary outcome is "definite or probable relapse" within 21 days after antibiotic completion. Secondary outcomes include definite and probable relapses at various timepoints until day 35 post-randomization, secondary infections, and adverse events. The neonatologist adjudicating probable relapses and lab personnel are blinded. Three hundred fifty subjects will be recruited in each arm, assuming a non-inferiority margin of 7%, one-sided alpha error 5%, and power of 90%. Analysis will be per protocol and by intention-to-treat. An independent Data Safety Monitoring Board monitors adverse events and will perform one interim analysis when 50% of expected primary outcomes have occurred or 50% of subjects have completed follow-up, whichever is earlier. O'Brien-Fleming criteria will be used to stop for mid-term benefit and Pocock's to stop for mid-term harm. A priori subgroup analyses are planned by birth weight categories, gram-stain status of pathogens, and radiological pneumonia. DISCUSSION: This trial will provide evidence to guide practice regarding optimum duration of antibiotics for culture-proven neonatal bacterial sepsis. If a 7-day regime is proved to be non-inferior to a 14-day regime, it is likely to reduce hospital stay, costs, adverse effects of drugs, and nosocomial infections. TRIAL REGISTRATION: Clinical Trials Registry India CTRI/2017/09/009743 . Registered on 13 September 2017.

Medication errors in neonatal intensive care unit of a tertiary care hospital in South India: A prospective observational study.

INTRODUCTION: Medication errors (MEs) can prolong hospital stay and are a cause of morbidity and mortality. Studies evaluating MEs and its determinants in Indian neonatal intensive care units (NICUs) are limited. Therefore, this study was done to assess the prevalence, characteristics, determinants, and outcomes of MEs in an Indian NICU setting. METHODOLOGY: A prospective observational study was conducted over a 1-year period (January-December 2016) among neonates receiving medications in NICU. Systematic random sampling was done, and data were collected using a semi-structured questionnaire after obtaining informed consent from the mother. An ME self-reporting system was also established. Data were analyzed using Chi-squared test and Student's t-test. Binary logistic regression was used to analyze the determinants of MEs. RESULTS: Among 269 babies included in the study, 57% (n = 154) were male babies with mean (standard deviation [SD]) birth weight of 2.59 kg (0.701). About 79% (n = 213/269) of the neonates were appropriate for gestational age. The mean (SD) duration of stay in NICU was 7.58 (5.07) days, and 67% of the babies had polypharmacy (use of ≥5 medications). The prevalence of MEs was 22% (95% confidence interval [CI]: 16.96%, 26.84%, n = 108) of all babies, of which only 2% (n = 2) were life threatening. Seventy-seven percent (n = 83) of these errors occurred during administration/preparation and 18% (n = 19) while prescribing. The significant determinants of MEs (adjusted odds ratio [95% CI]) include polypharmacy (4.126 [1.917-8.880]), duration of stay >7 days (1.335 [1.198-1.488]), and babies referred from outside (2.592 [1.217-5.521]). CONCLUSIONS: MEs were common in NICU setting. The occurrence of life-threatening MEs was minimal. Longer duration of hospital stay, polypharmacy, and babies born outside were significantly associated with occurrence of MEs.

Predictors of length of hospital stay among preterm infants admitted to neonatal intensive care unit: Data from a multicentre collaborative network from India (INNC: Indian National Neonatal Collaborative).

AIM: Prediction of length of stay (LOS) among preterm neonates is important for counselling of parents and for assessing neonatal intensive care unit (NICU) census and economic burden. The aim of this study is to evaluate perinatal and postnatal factors that influence LOS in preterm infants (25-33 weeks of gestation) admitted to participating NICUs of Indian National Neonatal Collaborative (INNC). METHODS: From the INNC database, the data which were prospectively entered using uniformed pre-defined criteria were analysed. RESULTS: A total of 3095 infants were included from 12 centres. Every week decrease in gestation increased LOS by 9 days. The median LOS for infants with gestational age of 25, 26, 27, 28, 29, 30, 31, 32 and 33 weeks were 86, 70, 62, 52, 40, 30, 23, 16 and 10 days, respectively. On multivariate analysis, abnormal antenatal umbilical artery doppler, severe small for gestational age (SGA), requirement of resuscitation, respiratory distress syndrome (RDS), seizures, sepsis, necrotising enterocolitis (NEC), major malformations and bronchopulmonary dysplasia (BPD) increased LOS by 5.4 (3.5-7.4), 21.6 (19-23.9), 4.7 (3.3-6.1), 3 (1.7-4.3), 15.2 (8.5-22.1), 11.2 (9.1-13.2), 9.8 (5.2-14.4), 8.8 (4.4-13.3) and 5.6 (0.5-10.7) days, respectively. CONCLUSIONS: Apart from lower gestation and birth weight, abnormal antenatal umbilical artery doppler, severe SGA, resuscitation need, major malformations, RDS, seizures, sepsis, NEC and BPD influenced LOS in preterm infants. In comparison with other networks or data from developed countries, LOS in our network was comparatively less for similar gestational age infants.

Therapeutic hypothermia for moderate and severe hypoxic ischaemic encephalopathy in newborns using low-cost devices - ice packs and phase changing material.

Background: Different methods have been used for therapeutic hypothermia for neonates with moderate-to-severe hypoxic ischaemic encephalopathy (HIE). As standard cooling devices are expensive, there is a need to establish the safety and efficacy of low-cost devices such as ice packs (IP) and phase changing material (PCM). Aim: To assess the efficacy and safety of therapeutic hypothermia (TH) and the clinico-laboratory profile of neonates who underwent cooling with IP or PCM. Methods: The study was retrospective. TH for moderate-to-severe HIE was initiated with IP between 2012 and 2014 and with PCM (MiraCradleTM) from September 2014. A standard protocol for inclusion and management during TH was used for all newborns. All data were collected by means of a local cooling registry. Results: Sixty-two cooled newborns (IP 29, PCM 33) were included in the study. Mean gestational age was 38.6 (1.7) weeks and mean birthweight 2920.6 g (450.7); 66.1% were inborn and 91.9% had moderate encephalopathy. Mean (SD) core temperature during cooling was 33.47°C (0.33) for PCM and 33.44°C (0.34) for IP. Adverse events observed during TH were thrombocytopenia (54.8%), coagulopathy (30.6%), shock (30.6%), skin changes (12.9%) and persistent pulmonary hypertension (8.1%). Forty-nine infants were discharged, two died and 11 were discharged against medical advice. TH was prematurely stopped in seven newborns with serious adverse events such as disseminated intravascular coagulation (DIC), gangrene and arrhythmia (IP 5, PCM 2). Conclusion: Low-cost devices are safe and effective alternatives for maintaining TH in low-resource settings with adequate monitoring. Abbreviations: DAMA, discharged against medical advice; DIC, disseminated intravascular coagulation; HELIX, Hypothermia for Encephalopathy in Low- and Middle-Income Countries Trial; HIE, hypoxic ischaemic encephalopathy; IP, ice packs; LMIC, low- and middle-income countries; NICHD, National Institute of Child Health and Human Development; PCM, phase changing; TH, therapeutic hypothermia (TH); TOBY, total body hypothermia for neonatal encephalopathy.

Umbilical cord milking in preterm neonates requiring resuscitation: A randomized controlled trial.

OBJECTIVE: To evaluate the effect of cord milking on short term morbidity and hematologic parameters at 6 weeks in preterm neonates requiring resuscitation. METHODS: This trial randomized preterm infants requiring resuscitation to milking group and no milking group. Multiple pregnancy, Rh negative mothers, hydrops, cord abnormalities were excluded. The primary outcome was hemoglobin and serum ferritin at 6 weeks of life. Secondary outcomes were common preterm morbidities and mortality. RESULTS: 60 neonates were included in the study. Infants in the milking group had higher hemoglobin (10.07 g/dl vs 8.9 g/dl; p 0.003) and higher serum ferritin level (244.8 ng/ml vs 148.5 ng/ml; p 0.04) compared to no milking group. CONCLUSIONS: In preterm neonates requiring resuscitation, umbilical cord milking results in higher hemoglobin and ferritin at 6 weeks of life. It can be a used as a placental transfusion strategy in preterm neonates requiring resuscitation with no significant adverse effects. CLINICAL TRIAL REGISTRATION: Clinical trials registry -India CTRI/2015/01/005436, www.ctri.nic.in.

Barriers and enablers to skin-to-skin contact at birth in healthy neonates - a qualitative study.

BACKGROUND: Skin to skin contact (SSC) at birth is the standard of care for newborns without risk factors. However, implementation of SSC at birth has been far from optimal. A qualitative study was undertaken to determine the barriers, enablers and potential solutions to implementation of SSC at birth in healthy newborn infants in a level III neonatal-care facility in Bangalore, India. METHODS: Consultants and residents/postgraduates (PG) from the departments of Obstetrics (n = 19) and Pediatrics (n = 14) and nurses (n = 8) in the labor room (LR) participated in the study. In depth interviews (IDI) and focus group discussions (FGD) were carried out with an interview guide and a moderators' guide containing inbuilt probes. Subjects of FGD were homogenous. All IDI and FGD were audio-taped, transcribed and analyzed using N VIVO version 9 (using free and tree nodes). Two authors separately coded the transcripts. Major and minor themes were identified. Rigor was ensured by triangulation and theoretical saturation. Informed consent and ethical approval was obtained. RESULTS: All subjects were aware of SSC at birth, some of its benefits and had practiced SSC. The major barriers identified were lack of personnel (nurses), time constraint, difficulty in deciding on eligibility for SSC, safety concerns, interference with clinical routines, and interdepartmental issues. Recall of an adverse event during SSC was also a major barrier. Furthermore, we found that most participants considered 1 h as impractical; and promoted 5-15 min SSC. Minor themes were gender bias of the newborn and cultural practices. The participants offered solutions such as assigning a helper exclusively for SSC, allowing a family member into the LR, continuing SSC after initial routines, antenatal counselling, constant reminders in the form of periodic sessions with audiovisual aids or posters in the obstetrics ward, training of new nurses and PG, and inclusion of SSC in medical and nursing curriculum. CONCLUSIONS: The major barriers to SSC at birth are lack of personnel, time constraint and safety concerns. Training, designated health personnel for SSC and teamwork are the key interventions likely to improve SSC at birth.

Probiotics for Promoting Feed Tolerance in Very Low Birth Weight Neonates - A Randomized Controlled Trial.

OBJECTIVE: To measure the efficacy of a probiotic formulation on time to reach full enteral feeds in VLBW (very low birth weight) newborns. DESIGN: Blinded randomized control trial. SETTING: A tertiary care neonatal intensive care unit (NICU) in Southern India between August 2012 to November 2013. PARTICIPANTS: 104 newborns with a birth weight of 750-1499 g on enteral feeds. INTERVENTION: Probiotic group (n=52) received a multicomponent probiotic formulation of Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium longum and Saccharomyces boulardii once a day at a dose of 1.25×109 CFU from the time of initiation of enteral feeds till discharge and the control group (n=52) received only breast milk. OUTCOME MEASURE: Time to reach full enteral feeds (150 mL/kg/day). RESULTS: The mean (SD) time to reach full enteral feeding was 11.2 (8.3) days in probiotic vs. 12.7 (8.9) in no probiotic group; (P=0.4), and was not significantly different between the two study groups. There was a trend towards lower necrotizing enterocolitis in the probiotic group (4% vs. 12%). CONCLUSION: Probiotic supplementation does not seem to result in significant improvement of feed tolerance in VLBW newborns.

Maintaining reduced noise levels in a resource-constrained neonatal intensive care unit by operant conditioning.

OBJECTIVE: To evaluate the efficacy of operant conditioning in sustaining reduced noise levels in the neonatal intensive care unit (NICU). DESIGN: Quasi-experimental study on quality of care. SETTING: Level III NICU of a teaching hospital in south India. PARTICIPANTS: 26 staff employed in the NICU. (7 Doctors, 13 Nursing staff and 6 Nursing assistants). INTERVENTION: Operant conditioning of staff activity for 6 months. This method involves positive and negative reinforcement to condition the staff to modify noise generating activities. MAIN OUTCOME MEASURES: Comparing noise levels in decibel: A weighted [dB (A)] before conditioning with levels at 18 and 24 months after conditioning. Decibel: A weighted accounts for noise that is audible to human ears. RESULTS: Operant conditioning for 6 months sustains the reduced noise levels to within 62 dB in ventilator room 95% CI: 60.4 - 62.2 and isolation room (95% CI: 55.8 - 61.5). In the preterm room, noise can be maintained within 52 dB (95% CI: 50.8 - 52.6). This effect is statistically significant in all the rooms at 18 months (P = 0.001). At 24 months post conditioning there is a significant rebound of noise levels by 8.6, 6.7 and 9.9 dB in the ventilator, isolation and preterm room, respectively (P =0.001). CONCLUSION: Operant conditioning for 6 months was effective in sustaining reduced noise levels. At 18 months post conditioning, the noise levels were maintained within 62 dB (A), 60 dB (A) and 52 dB (A) in the ventilator, isolation and pre-term room, respectively. Conditioning needs to be repeated at 12 months in the ventilator room and at 18 months in the other rooms.

Low cost calibrated mechanical noisemaker for hearing screening of neonates in resource constrained settings.

BACKGROUND & OBJECTIVES: There is a need to develop an affordable and reliable tool for hearing screening of neonates in resource constrained, medically underserved areas of developing nations. This study valuates a strategy of health worker based screening of neonates using a low cost mechanical calibrated noisemaker followed up with parental monitoring of age appropriate auditory milestones for detecting severe-profound hearing impairment in infants by 6 months of age. METHODS: A trained health worker under the supervision of a qualified audiologist screened 425 neonates of whom 20 had confirmed severe-profound hearing impairment. Mechanical calibrated noisemakers of 50, 60, 70 and 80 dB (A) were used to elicit the behavioural responses. The parents of screened neonates were instructed to monitor the normal language and auditory milestones till 6 months of age. This strategy was validated against the reference standard consisting of a battery of tests - namely, auditory brain stem response (ABR), otoacoustic emissions (OAE) and behavioural assessment at 2 years of age. Bayesian prevalence weighted measures of screening were calculated. RESULTS: The sensitivity and specificity was high with least false positive referrals for 70 and 80 dB (A) noisemakers. All the noisemakers had 100 per cent negative predictive value. 70 and 80 dB (A) noisemakers had high positive likelihood ratios of 19 and 34, respectively. The probability differences for pre- and post- test positive was 43 and 58 for 70 and 80 dB (A) noisemakers, respectively. INTERPRETATION & CONCLUSIONS: In a controlled setting, health workers with primary education can be trained to use a mechanical calibrated noisemaker made of locally available material to reliably screen for severe-profound hearing loss in neonates. The monitoring of auditory responses could be done by informed parents. Multi-centre field trials of this strategy need to be carried out to examine the feasibility of community health care workers using it in resource constrained settings of developing nations to implement an effective national neonatal hearing screening programme.

Efficacy of a low cost protocol in reducing noise levels in the neonatal intensive care unit.

OBJECTIVE: To examine the effectiveness and cost of implementing a noise reduction protocol in a level III neonatal intensive care unit (NICU). METHODS: A prospective longitudinal study was done in a level III NICU, wherein a noise reduction protocol that included behavioral and environmental modification was implemented. The noise levels were measured sequentially every hour for 15 days before and after this intervention. The statistical significance of the reduction in noise levels after implementation of the protocol was tested by paired sample student's t-test. Cost was calculated using the generalized cost effectiveness model of the World Health Organisation. The present study has 80% power with 95% confidence to measure 2 dB differences between groups for the maximum recommended of 50 dB. RESULTS: The protocol in the present study reduced noise levels in all the rooms of the NICU to within 60 dB with high statistical significance (p< 0.001). The extent of noise reduction in the rooms of the NICU was as follows: ventilator room by 9.58 dB (95% confidence interval: 6.73-12.42, p < 0.001), stable room by 6.54 dB (95% confidence interval: 2.92-4.16, p < 0.001), isolation room by 2.26 dB (95% confidence interval: 1.21-3.30, p < 0.001), pre-term room by 2.37 dB(95% confidence interval: 1.22-3.51, p < 0.001) and extreme preterm room by 2.09 dB (95% confidence interval: 1.14-3.02, p < 0.001). The intervention was most cost-effective in the ventilator room, requiring Rs. 81.09 to reduce 1 dB and least effective in the extreme pre-term room requiring Rs. 371.61 to reduce 1 dB. CONCLUSION: The high efficacy and affordability of noise reduction protocols justify the need for implementation of these measures as a standard of care in neonatal intensive care units.

Spectral analysis of noise in the neonatal intensive care unit.

OBJECTIVE: To perform spectral analysis of noise generated by equipments and activities in a level III neonatal intensive care unit (NICU) and measure the real time sequential hourly noise levels over a 15 day period. METHODS: Noise generated in the NICU by individual equipments and activities were recorded with a digital spectral sound analyzer to perform spectral analysis over 0.5 - 8 KHz. Sequential hourly noise level measurements in all the rooms of the NICU were done for 15 days using a digital sound pressure level meter . Independent sample t test and one way ANOVA were used to examine the statistical significance of the results. The study has a 90 % power to detect at least 4 dB differences from the recommended maximum of 50 dB with 95 % confidence. RESULTS: The mean noise levels in the ventilator room and stable room were 19.99 dB (A) sound pressure level (SPL) and 11.81 dB (A) SPL higher than the maximum recommended of 50 dB (A) respectively ( p < 0.001). The equipments generated 19.11 dB SPL higher than the recommended norms in 1 - 8 KHz spectrum. The activities generated 21.49 dB SPL higher than the recommended norms in 1 - 8 KHz spectrum ( p< 0.001). The ventilator and nebulisers produced excess noise of 8.5 dB SPL at the 0.5 KHz spectrum. CONCLUSION: Noise level in the NICU is unacceptably high .Spectral analysis of equipment and activity noise have shown noise predominantly in the 1 - 8 KHz spectrum. These levels warrant immediate implementation of noise reduction protocols as a standard of care in the NICU.

Kangaroo mother care for low birth weight infants: a randomized controlled trial.

OBJECTIVE: To compare the effect of Kangaroo mother care (KMC) and conventional methods of care (CMC) on growth in LBW babies (> 2000 g). STUDY DESIGN: Randomized controlled trial. SETTING: Level III NICU of a teaching institution in western India. SUBJECTS: 206 neonates with birth weight < 2000 g. INTERVENTION: The subjects were randomized into two groups: the intervention group (KMC-103) received Kangaroo mother care. The control group (CMC: 103) received conventional care. OUTCOME MEASURES: Growth, as measured by average daily weight gain and by other anthropometrical parameters at 40 weeks postmenstrual age in preterm babies and at 2500 g in term SGA infants was assessed. RESULTS: The KMC babies had better average weight gain per day (KMC: 23.99 g vs CMC: 15.58 g, P< 0.0001). The weekly increments in head circumference (KMC: 0.75 cm vs CMC: 0.49 cm, P = 0.02) and length (KMC: 0.99 cm vs CMC: 0.7 cm, P = 0.008) were higher in the KMC group. A significantly higher number of babies in the CMC group suffered from hypothermia, hypoglycemia, and sepsis. There was no effect on time to discharge. More KMC babies were exclusively breastfed at the end of the study (98% vs 76%). KMC was acceptable to most mothers and families at home. CONCLUSION: Kangaroo mother care improves growth and reduces morbidities in low birth weight infants. It is simple, acceptable to mothers and can be continued at home.