Resuscitation with Intact Cord Versus Clamped Cord in Late Preterm and Term Neonates: A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of intact cord versus clamped cord resuscitation on the physiologic transition of neonates receiving positive-pressure ventilation (PPV) at birth. STUDY DESIGN: This open-label, parallel-group, randomized controlled superiority trial was conducted in a tertiary care hospital in India. Neonates born at ≥34 weeks of gestation after a complicated pregnancy or labor were randomized just before birth to receive resuscitation according to the Neonatal Resuscitation Program algorithm with either an intact cord (intact cord resuscitation group) or after early cord clamping (early cord clamping resuscitation group). The allocated study intervention was administered if the neonate needed PPV at birth. The primary outcome was expanded Apgar score at 5 minutes after birth. RESULTS: Birth weight, gestational age, and the incidence of pregnancy complications were similar in the 2 study groups. The proportion of neonates who received PPV was lower in the intact cord resuscitation group (28.7% vs 36.5%, P = .05; relative risk, 0.79; 95% CI, 0.61-1.01). Among neonates who received PPV, the expanded Apgar score at 5 minutes was significantly higher in the intact cord resuscitation group (median, 15 [IQR, 14-15] vs 14 [IQR, 13-15]; P < .001). The expanded Apgar score at 10 minutes, Apgar scores at 5 and 10 minutes, and oxygen saturation at 1, 5, and 10 minutes were also higher in the intact cord resuscitation group. CONCLUSION: In late preterm and term neonates, resuscitation with an intact cord results in better postnatal physiologic transition than the standard practice of resuscitation after immediate cord clamping. TRIAL REGISTRATION: Clinical Trial Registry of India (www.ctri.nic.in); trial registration no. CTRI/2020/02/023379.

Population pharmacokinetics of ciprofloxacin in newborns with early onset neonatal sepsis and suspected meningitis.

BACKGROUND: Neonatal Sepsis accounts for significant proportion of neonatal mortality globally. Ciprofloxacin can be used as an effective antimicrobial against common causative agents of neonatal sepsis. However, there is only limited information about its pharmacokinetic distribution in plasma and Cerebrospinal fluid (CSF) of neonates. METHODS: Plasma and CSF samples were taken using a sparse sampling technique from neonates who received at least one dose of intravenous ciprofloxacin. Ciprofloxacin levels were analysed using high-performance liquid chromatography (HPLC). Population pharmacokinetic analysis was conducted using a non-linear mixed-effects modelling using Pumas® (Pharmaceutical Modelling and Simulation) package (Version 2.0). RESULTS: 53 neonates were enroled in the study of whom; 9 (17%) had meningitis. The median concentration of ciprofloxacin in CSF was 1.4 (0.94-2.06) ug/ml and plasma was 2.94 (1.8-5.0) ug/ml. A one-compartment model with first-order elimination fitted the data. Body weight was found to be a significant covariate on volume of distribution (Vd). Simulations based on the final model suggest that dose of 10 mg/kg, intravenous b.d may not be able to achieve the desirable indices. CONCLUSIONS: One compartment model with weight as a covariate explained the available data. Further studies with modified sampling strategy, larger sample size and variable dose levels are needed.

Closed versus open endotracheal tube suction in mechanically ventilated neonates: a randomized controlled trial.

This study aimed to evaluate the effect of closed versus open endotracheal tube suction in reducing ventilator-associated pneumonia in mechanically ventilated neonates. In this open-label, parallel-group, randomized controlled trial with allocation concealment, ventilated neonates (≥ 28 weeks and ≥ 800 g) were either allocated to the closed-suction group (n = 41) or open-suction group (n = 39). The ventilator circuit of the babies enrolled in the closed-suction group was attached to the closed-suction catheter on the requirement of their first suction, and it was changed after every 48 h or earlier if visibly soiled whereas babies enrolled in the open-suction group were suctioned with a new suction catheter each time they require suction. The primary outcome was the incidence of VAP per 1000 days. Baseline maternal and neonatal characteristics were comparable between the two groups. The proportion of neonates with VAP in the closed-suction group was 3 (7.3%) and 1 (2.6%) in the open-suction group with an RR of 2.8 (95% CI: 0.30-26.28) and a p-value of 0.35. The incidence of VAP in the closed-suction group was 3.9 per 1000 ventilator days and 1.3 per 1000 ventilator days in the open-suction group. The incidence of clinical VAP/1000 ventilator days was 33.63 ± 22.96 in the closed-suction group and 28.67 ± 12.32 in the open-suction group with a mean difference of 5 (95% CI: - 3.26 to 13.26) and p-value of 0.24. CONCLUSION: In a unit with a low incidence of VAP, the effect of the endotracheal suction method alone did not impact the occurrence of VAP in the study population. CLINICAL TRIAL REGISTRATION: CTRI/2020/03/023679; Date: 17.02.2020. WHAT IS KNOWN: • Better physiological stability of the closed-suctioning method on short-term measures including noticeably fewer episodes of hypoxia, a smaller drop in TcPO2 levels, and less variability in heart rate and bradycardia episodes. WHAT IS NEW: • In a unit with a low incidence of VAP in the neonates, randomized control trial studying the effect of the endotracheal suction method alone did not impact the occurrence of VAP amongst the study population.

Supplementation of mother's own milk with term versus preterm donor human milk: a randomized controlled trial.

The purpose of this is to evaluate the effect of supplementation of enteral feed volume with preterm versus term donor human milk (DHM) on short-term physical growth in very low birth weight (VLBW) neonates. In this open-label, variable block-sized, superiority, randomized controlled trial with allocation concealment, VLBW neonates with insufficient volume of mother's own milk (MOM) were assigned to receive either preterm (n = 48) or term (n = 54) DHM till discharge. Preterm DHM was defined as the breast milk expressed within 28 days of delivery at ≤ 34 weeks of gestation. The primary outcome was days to regain birth weight. Maternal and neonatal demographic variables were comparable in the two study groups. Days to regain birth weight were significantly more in the preterm DHM group, 17.4 (7.7) vs 13.6 (7.2) days, mean difference (95% CI) being 3.74 (0.48-7.0) days, P = 0.02). The proportion of MOM use was 82% in preterm vs 91.1%, P = 0.03 in the term milk group. Duration of skin-to-skin contact was also significantly lower in the preterm vs term milk group, the median (IQR) was 4 (0, 6) vs 4 (2, 6) hours/day, P < 0.01. However, bronchopulmonary dysplasia was higher in the preterm milk group (13% vs. 4%, P = 0.17). The velocity of gain in weight was similar in the two groups from week 1-3 but higher in the term DHM supplementation group during the 4th week. Conclusion: Supplementing MOM with preterm DHM did not result in a faster regaining of birth weight. Trial registration: CTRI/2020/02/023569; Date: 17.02.2020.

Peripheral Perfusion Index as a Marker of Sepsis in Preterm Neonates.

BACKGROUND: Neonatal sepsis is a major contributor to neonatal mortality in India. Blood culture, the gold standard for the diagnosis of sepsis takes 48-72 h while the serological markers have suboptimal diagnostic test characteristics. Perfusion index (PI) is a real time, non-invasive marker that can detect microcirculatory changes before other clinical manifestation of sepsis. OBJECTIVE: To determine the diagnostic accuracy of PI in detecting hospital-acquired sepsis before overt clinical manifestations. STUDY DESIGN: A prospective observational study conducted in the Neonatal Intensive Care Unit (NICU) of a tertiary care hospital. PARTICIPANTS: Preterm neonates admitted to NICU. METHODS: PI was continuously monitored in all enrolled neonates. Clinical sepsis was defined using the NeonatalKrankenhaus-Infektions-Surveillance-System (NeoKISS). The time of fall of PI below 0.88 and time of clinical sepsis as per NeoKISS were noted and the difference was calculated. RESULTS: Among 65 preterm neonates (gestational age: 31.5 ± 2.6 weeks, birth weight: 1350, IQR 1100-1700 g), a total of 86 events of suspected sepsis were noted, of which 69 were sepsis screen positive. Fifteen events were associated with culture positive sepsis. PI yielded a sensitivity of 89.47% (95% CI 78.48-96.04%), specificity of 56% (95% CI 34.93-75.60%), positive predictive value of 82.26% (95% CI 74.70-87.92%) and negative predictive value of 70% (95% CI 50.36-84.29%) in detection of hospital-acquired sepsis. CONCLUSION: PI might serve as an early, non-invasive marker of hospital-acquired sepsis in preterm neonates.

Extended Pulse Oximetry Screening in Healthy Neonates.

Predischarge pulse oximetry screening (POS) is recommended to pick up critical congenital heart diseases in apparently well neonates. However, it is possible that cases may be missed during the early POS in the presence of delayed closure of the ductus arteriosus. Repeat POS in the second week of life was found to be helpful and feasible for early detection of pathological states causing hypoxemia in seemingly well neonates. Studies with larger sample size are recommended to establish the role of an additional POS in the second week for enhanced CCHD detection.

Comparative efficacy of volume expansion, inotropes and vasopressors in preterm neonates with probable transitional circulatory instability in the first week of life: a systematic review and network meta-analysis.

BACKGROUND: There exists limited agreement on the recommendations for the treatment of transitional circulatory instability (TCI) in preterm neonates OBJECTIVE: To compare the efficacy of various interventions used to treat TCI METHODS: Medline and Embase were searched from inception to 21st July 2023. Two authors extracted the data independently. A Bayesian random effects network meta-analysis was used. Recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. INTERVENTIONS: Dopamine, dobutamine, epinephrine, hydrocortisone, vasopressin, milrinone, volume and placebo. MAIN OUTCOME MEASURES: Mortality, major brain injury (MBI) (intraventricular haemorrhage > grade 2 or cystic periventricular leukomalacia), necrotising enterocolitis (NEC) ≥stage 2 and treatment response (as defined by the author). RESULTS: 15 Randomized Controlled Trials (RCTs) were included from the 1365 titles and abstracts screened. Clinical benefit or harm could not be ruled out for the critical outcome of mortality. For the outcome of MBI, epinephrine possibly decreased the risk when compared to dobutamine and milrinone (very low certainty). Epinephrine was possibly associated with a lesser risk of NEC when compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Dopamine was possibly associated with a lesser risk of NEC when compared with dobutamine (very low certainty). Vasopressin possibly decreased the risk of NEC compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Clinical benefit or harm could not be ruled out for the outcome response to treatment. CONCLUSIONS: Epinephrine may be used as the first-line drug in preterm neonates with TCI, the evidence certainty being very low. We suggest future trials evaluating the management of TCI with an emphasis on objective criteria to define it.

Quality improvement initiative for a sustained increase in human milk donation during the hospital stay.

BACKGROUND: The demand for donors' human milk is much more than the availability of the same due to the myriad challenges faced during the collection process. METHODS: Baseline milk volume donation done in a human milk bank facility located in tertiary care government institute in a low-middle income country was assessed. It was initially aimed to increase the absolute quantity of milk volume donation by 30% over a period of 6 months, which was subsequently continued following COVID-19 emergence (over another 12 months) along with a particular emphasis on the sustenance of milk donation activities. INTERVENTIONS: Counselling of both the healthcare workers and stakeholders, standardising the timing of milk donation and other policies, equipment in proportion to demand and supply and addition of human resource were done as a multiprong approach to have sustained increase in human milk donation. RESULTS: The median control line (MCL) showed a shift of 27.8%; from a baseline of 5032 mL to 6971 mL during intervention phase I comprising of five plan do study act cycles spread over a period of 6 months. During the sustenance phase I even though the monthly collection was non-uniform, there was a further 16% upward shift in MCL to 8122 mL. During the second intervention phase, each component of the Ishikawa diagram was worked on (people, policy, place, procedure) resulting in a more than 100% increase from sustenance phase I taking the MCL to 17 181 mL with an overall increase of 3.41 times from the baseline. CONCLUSION: Dedicated counselling and constant motivation have been conventionally considered as the utmost measure to increase milk volume donation in milk bank. Our study highlights the need to introduce scheduled timings along with sufficient equipment and manpower to overcome the shortage of milk donation in human milk bank facilities.

Immediate skin-to-skin contact versus care under radiant warmer at birth in moderate to late preterm neonates - A randomized controlled trial.

OBJECTIVE: To compare the effect of immediate care at birth in skin-to-skin contact (SSC) or under a radiant warmer on cardiorespiratory stability at 60 minutes of age in moderate-to-late preterm neonates. METHODS: In this open-label, parallel-group, randomized controlled trial, neonates born at 330/7 to 366/7 weeks of gestation by vaginal delivery and breathing or crying were randomized to receive care at birth in SSC (n = 50) or under a radiant warmer (n = 50). In the SSC group, immediate care at birth including drying and clearing of the airway was provided in SSC over the mother's abdomen. SSC was maintained for an observational period of 60 minutes after birth. In the radiant warmer group, care at birth and post-birth observation was performed under an overhead radiant warmer. The primary outcome of the study was the stability of the cardio-respiratory system in late preterm infants (SCRIP) score at 60 minutes of age. RESULTS: Baseline variables were similar in the two study groups. The SCRIP score at 60 minutes of age was similar in the two study groups (median: 5.0, IQR: 5-6 vs. 5.0, 5-6). The mean axillary temperature at 60 minutes of age was significantly lower in the SSC group (°C; 36.4 ± 0.4 vs. 36.6 ± 0.4, P = 0.004). CONCLUSION: It was feasible to provide immediate care at birth in moderate and late preterm neonates while being positioned in SSC with the mother. However, in comparison to care under a radiant warmer, this did not lead to better cardiorespiratory stability at 60 minutes of age. TRIAL REGISTRATION: Clinical Trial Registry of India (CTRI/2021/09/036730).

Assessing the Incidence of New-onset Diabetes Mellitus with Statin Use: A Systematic Review of the Systematic Reviews and Meta-analyses.

Statin use has been linked with new-onset diabetes mellitus (NODM). In the present systematic review, we aimed to determine the incidence of NODM with statin use by assessing and summarizing the data generated by different systematic reviews and metaanalyses published on this topic. We conducted a systematic review of systematic reviews and meta-analyses using a pre-defined study protocol. Two authors independently performed a literature search using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies reporting data on statin use and NODM incidence and screened and extracted data for the outcomes of interest. The Assessing the Methodological Auality of Systematic Reviews 2 (AMSTAR 2) checklist was used to evaluate the quality of the included systematic reviews and meta-analyses. The initial search yielded 621 potential records, and 16 relevant systematic reviews and meta-analyses were included in the present systematic review. The included studies showed an increase in the risk of NODM with statin use. In particular, rosuvastatin and atorvastatin were associated with NODM in many systematic reviews or meta-analyses; however, pravastatin and pitavastatin were found to be associated with lower or no risk. We observed a positive trend of development of NODM with statin use became more evident with advancing years as more number of studies were added. Intensive doses of statins and use in older subjects were found to be important risk factors for NODM. Finally, the quality assessment revealed that the included systematic reviews and metaanalyses were of critically low or low quality. We concluded that statin use carries a risk of causing NODM. Statins should not be discouraged in anticipation of NODM. However, glycaemic monitoring should be encouraged with the on-going statin therapy. Furthermore, clinical studies addressing the use of statins and the incidence of NODM as their primary objective should be planned.

Severe Pulmonary Arteriopathy in a Neonate with Congenital Rubella Syndrome and Patent Ductus Arteriosus.

Neonates with congenital rubella syndrome (CRS) are known to have associated congenital cardiac malformations. Patent ductus arteriosus (PDA) is one the most common cardiac anomalies associated with CRS. PDA refractory to medical management and associated with ventilatory dependence is considered for surgical ligation. However, the management of PDA can be challenging in the presence of underlying lung disease or pulmonary vascular disease. Outcomes after closure in neonates are dependent upon age, weight, nutritional status, pre-operative pulmonary arterial hypertension and presence of chronic lung disease. We present a neonate with CRS who required surgical PDA closure. The neonate developed severe pulmonary arterial hypertension which led to fatal outcome. The clinical course is corroborated with histo-pathological changes observed on the autopsy of this neonate.

Reducing Healthcare-associated Infections in Neonates by Standardizing and Improving Compliance to Aseptic Non-touch Techniques: A Quality Improvement Approach.

OBJECTIVE: To standardize and improve compliance to Aseptic non-touch techniques (ANTT) for commonly performed procedures in Neonatal intensive care unit (NICU) through application of Model for improvement, and study its impact on Healthcare-associated infection (HCAI) rates. DESIGN: Quality improvement project utilizing multiple Plan-Do-Study-Act (PDSA) cycles. SETTING: Tertiary-care neonatal unit. PARTICIPANTS: All resident doctors and nurses working in neonatal unit were subjects for assessment of compliance to ANTT. All admitted neonates staying in hospital for more than 48 hours were subjects for HCAI data collection. PROCEDURE: Most frequently performed procedures in NICU were identified and pictorial Standard Operating Procedures (SOP) were developed. Implementation and uptake was reinforced by means of PDSA cycles. Compliance to ANTT was assessed as proportion of components to which adherence was documented. Trend of HCAI rates in unit were analyzed using process control charts. MAIN OUTCOME MEASURE: Change in compliance to ANTT for most frequently performed procedures. RESULTS: Significant improvement in compliance to ANTT practices was observed, specifically in use of procedure tray/trolley (16% to 49%, P=0.001), iv hub scrubbing (0% to 60%, P=0.001), local skin cleaning (33% to 67%, P=0.004), personal protective equipment use (55% to 80%, P=0.02) and disposal (27% to 51%, P=0.03), use of non-touch technique (50% to 70%, P=0.001) and reduction in key part contamination (45% to 31%, P=0.03). A modest decrease in HCAI rates was seen in the short period of observation after implementation. CONCLUSIONS: Substantial improvements in compliance to aseptic non-touch techniques can be ensured by adopting a combination of initial intensive teaching and sustaining through multiple PDSA cycles, targeting specific areas revealed by audits.