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.

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).

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.

Systemic biomarkers of retinopathy of prematurity in preterm babies.

PURPOSE: Retinopathy of prematurity (ROP) progression is an inter-play of various perinatal and neonatal angiogenic and inflammatory cytokines. A small subset of ROP progresses to ROP requiring treatment. The present study was conducted with the aim to determine whether levels of IL-6, IL-8 and VEGF in serum and urine at the time of first ROP screening visit could be a biomarker for the prediction of development of treatable ROP. METHOD: Prospective single-center observational study of preterm babies screened for ROP. Blood and urine samples were collected as a part of routine sampling at initial ROP screening visit and stored at -80 °C for further processing. The babies were followed up and grouped into 'Group A' comprising of 35 babies who developed treatable ROP and 'Group B' comprising of 36 babies with regressed ROP or no ROP. The evaluation of blood and urine samples was done for IL6, IL8 and VEGF by solid-phase sandwich RayBio® Human ELISA kit. RESULTS: The median serum values for IL-6, IL-8 and VEGF in Group A and Group B were 5.8 pg/ml (IQR 1.5,128.5) and 8.7 pg/ml (IQR 1.5,30.5), 55.9 pg/ml (IQR 28.0, 392.9) and 27.0 pg/ml (IQR 20.5,444.9) and 26.6 pg/ml (IQR 6.3, 39.4) and 30.0 pg/ml (IQR9.2,70.3), respectively. Group A had significantly increased levels of IL-8 (p < 0.05). However, AUROC curve for serum IL-8 demonstrated suboptimal discriminating ability. CONCLUSION: Babies developing ROP requiring treatment had significantly increased levels of IL-8 in the serum at the time of initial screening. However, it could not serve as predictor for treatable ROP.

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.

Non-contact respiratory rate monitoring using thermal and visible imaging: a pilot study on neonates.

Respiratory rate (RR) monitoring is essential in neonatal intensive care units. Despite its importance, RR is still monitored intermittently by manual counting instead of continuous monitoring due to the risk of skin damage with prolonged use of contact electrodes in preterm neonates and false signals due to displacement of electrodes. Thermal imaging has recently gained significance as a non-contact method for RR detection because of its many advantages. However, due to the lack of information in thermal images, the selection and tracking of the region of interest (ROI) in thermal images for neonates are challenging. This paper presents the integration of visible (RGB) and thermal (T) image sequences for the selection and tracking of ROI for breathing rate extraction. The deep-learning based tracking-by-detection approach is employed to detect the ROI in the RGB images, and it is mapped to the thermal images using the RGB-T image registration. The mapped ROI in thermal spectrum sequences gives the respiratory rate. The study was conducted first on healthy adults in different modes, including steady, motion, talking, and variable respiratory order. Subsequently, the method is tested on neonates in a clinical settings. The findings have been validated with a contact-based reference method.The average absolute error between the proposed and belt-based contact method in healthy adults reached 0.1 bpm and for more challenging conditions was approximately 1.5 bpm and 1.8 bpm, respectively. In the case of neonates, the average error is 1.5 bpm, which are promising results. The Bland-Altman analysis showed a good agreement of estimated RR with the reference method RR and this pilot study provided the evidence of using the proposed approach as a contactless method for the respiratory rate detection of neonates in clinical settings.

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.

Improving the Quality of Health Care in Special Neonatal Care Units of India: A Before and After Intervention Study.

BACKGROUND: We evaluated the efficacy of training health care workers (HCWs) in point-of-care quality improvement (POCQI) and a preterm newborn health care package (PHCP), followed by remote mentoring and supportive supervision in improving health care practices, neonatal survival, and morbidities in special neonatal care units (SNCUs). METHODS: This pre- and postintervention quality improvement study was conducted at 3 SNCUs in Madhya Pradesh, India from February 2017 to February 2019. Clinical care teams comprising doctors and nurses from the study sites were trained in POCQI and the PHCP. The teams identified, prioritized, and analyzed problems and designed quality improvement initiatives at their respective health facilities. Change ideas were tested by the local teams using sequential plan-do-study-act cycles. Facilitators maintained contact with the teams through quarterly review meetings, fortnightly videoconferencing, on-demand phone calls, and group chat service. State SNCU coordinators made follow-up visits to supplement coaching. Study research staff independently collected data on admissions, health care practices, and outcomes of neonates. FINDINGS: A total of 156 HCWs were trained in the POCQI methodology and PHCP. Sixteen quality improvement projects were formulated and implemented. Among 13,821 enrolled neonates (birth weight 2275±635 g; gestation: 35.8±2.8 weeks), improvement was seen in reduction of use of oxygen (36.1% vs. 48.0%; adjusted odds ratio [aOR]=0.60, 95% confidence interval [CI]=0.55, 0.66), antibiotics (29.4% vs. 39.0%; aOR=0.76, 95% CI=0.68, 0.85), and dairy milk (33.8% vs. 49.4%; aOR=0.34, 95% CI=0.31 to 0.38). Enteral feeds were started within 24 hours of admission in a larger number of neonates, resulting in fewer days to reach full feeds. There was no effect on survival at discharge from the hospital (aOR=0.93; 95% CI=0.80, 1.09). CONCLUSION: A collaborative cross-learning quality improvement approach with remote mentoring, coaching, and supportive supervision was successful in improving the quality of care at SNCUs.

Evaluation of double lung point sign as a marker for transient tachypnoea of the newborn in preterm.

Purpose: The study was conducted to diagnose transient tachypnoea of the newborn (TTN) in the early stage using ultrasonography and to estimate the sensitivity and specificity of double lung point (DLP) sign in diagnosing TTN. Material and methods: The study population included premature neonates with respiratory distress, admitted in the neonatal intensive care unit from December 2017 to June 2019, who fulfilled the inclusion criteria. A total of 100 patients were included in the study, and they underwent lung ultrasonography within 6 hours of birth. Inclusion criteria were as follows: preterm babies born < 37 weeks of gestation presenting with respiratory distress within 6 hours, clinically diagnosed with TTN and other causes like respiratory distress syndrome and pneumonia. Term neonates and neonates with congenital malformations and trauma were excluded from the study. Preterms with respiratory distress were enrolled in the study. Based on the clinical findings and laboratory investigations, clinical diagnosis was made by the paediatrician. After obtaining informed consent, ultrasonography of bilateral chest was performed using a Philips HD7 XE and a Sonoscape S2 portable ultrasound machine with a linear transducer (6-12 MHz) within 6 hours of birth. Results: The mean gestational age was 33.0 ± 1.9 weeks. Double lung point sign was present in 55 preterm neonates in our study. It was most common in bilateral posterior lung fields. The sensitivity and specificity of DLP in diagnosing TTN was 85% and 100%, respectively. Conclusions: It was found in our study that double lung point sign is the primary ultrasonographic characteristic of TTN, and ultrasonography can almost accurately diagnose TTN in early stages.