Normative Values of Cerebral Blood Flow Velocities in Very Low Birth Weight Neonates During First 28 Days of Life.

OBJECTIVE: To determine normative values of cerebral blood flow (CBF) velocities in very low birth weight (VLBW) neonates during first 28 days of life. METHODS: In this prospective observational study, doppler assessment of CBF velocities was performed from the anterior cerebral artery (ACA), middle cerebral artery (MCA) and basilar artery (BA) at 2-8 hours, 24 hours, day 3, 7, 14 and 28 of life. Neonates with gross congenital malformations, those requiring extensive resuscitation at birth, mechanical ventilation with mean airway pressure >12 mbar, requiring inotropes, or those who developed intraventricular hemorrhage (Grade II or more) were excluded. RESULTS: A total of 103 VLBW neonates were enrolled, in whom 1178 doppler measurements were recorded. The mean (SD) peak systolic velocity, end diastolic velocity and mean velocity (cm/s) in ACA increased from 26.53 (8.56) to 51.35 (9.36), 9.22 (2.91) to 13.9 (3.24) and 17.75 (3.97) to 25.84 (3.27) respectively from 2 to 8 hours to day 28 of life. In MCA and BA also, CBF velocities increased with post-natal age. CONCLUSION: We report normative data of CBF velocities in VLBW neonates in first 28 days of life.

Comparison of Levosimendan Versus Milrinone After the Arterial Switch Operation for Infants ≤3†kg.

Background: Various inotropes and inodilators have been utilized to treat low cardiac output syndrome after the arterial switch operation. The use of levosimendan, a calcium sensitizer has been limited in this setting. This study compares the effects of levosimendan with milrinone in managing low cardiac output after the arterial switch operation. Methods: A retrospective, comparative study was conducted in a tertiary care hospital on patients weighing up to 3 kg undergoing the arterial switch operation between January 2017 and January 2022. Patients received a loading dose followed by continuous infusion of either levosimendan or milrinone. Echocardiographic, hemodynamic and biochemical parameters were compared. Results: Forty-three patients received levosimendan and 42 patients received milrinone as the primary test drug. Cardiac index of less than 2.2 L/min/m2 on postoperative day 1 and 2 was found in 9.3% and 2.3% of patients receiving levosimendan versus 26.2% and 11.9% in those receiving milrinone, respectively (P = .04 and .08, respectively). Early lactate-clearance and better central venous oxygen saturations were noted in the levosimendan group. Prevalence of acute kidney injury was higher in the milrinone group (50% vs 28%; P = .03). Use of peritoneal dialysis in the milrinone group versus levosimendan was 31% and 16.3%, respectively (P = .11). There was no difference in hospital mortality between the groups (milrinone, 3; levosimendan, 2, P = .62). Conclusions: Levosimendan is safe and as effective as milrinone to treat low cardiac output syndrome occurring in neonates after the arterial switch operation. In addition we found that levosimendan was renal protective when compared with milrinone.

Echocardiographic characteristics in neonates with septic shock.

Clinical parameters used for hemodynamic assessment and titration of vasopressor therapy in neonates with septic shock have several limitations. Functional echocardiography is an emerging tool for bedside assessment of cardiac function and may be useful for diagnosis of shock and assessing the response to therapy. Data regarding echocardiographic parameters in neonates with shock is lacking. This prospective observational study was conducted in a Level III NICU with the primary objective of comparing echocardiographic characteristics of neonates with septic shock at diagnosis, following fluid boluses, and after maximum inotropic support [A1]. Additionally, we compared these characteristics with those of healthy stable neonates who were gestation and postnatal age-matched. A total of 36 neonates with septic shock and 30 gestation and postnatal age-matched controls were enrolled. The mean (SD) gestation and birth weight of neonates with septic shock were 30.6 (4.0) weeks and 1538 (728) g, respectively. Gram-negative bacilli constituted 78.9% of all isolates. At presentation, there was no significant difference between neonates with shock and controls in terms of ventricular outputs, shortening fraction, ratio of early to late diastolic trans-mitral flow velocity, and myocardial performance indices. The distensibility index of inferior vena cava was higher in neonates with shock compared to controls, (17% vs 10%, (p < 0.01)). Left ventricular output was 209 (92) and 227 (102) ml/kg/min (p = 0.53) and right ventricular output was 427 (203) and 459 (227) ml/kg/min, (p = 0.03), respectively, before and after inotropic therapy.     Conclusion: Echocardiographic parameters may not differentiate neonates with septic shock from hemodynamically stable neonates. Neonates with shock associated with predominantly gram-negative sepsis are not able to augment cardiac functions, either at the onset or after administration of inotropes.      Trial registration: (CTRI/2017/12/010766). What is known: • For neonates with shock, echocardiography is becoming increasingly popular as an objective method of evaluating hemodynamics. • In healthy preterm neonate, cardiac output has been known to increase in response to altered hemodynamics during states of increased oxygen demand. What is new: •  In the setting of septic shock induced by gram-negative organisms, echocardiographic parameters are less likely to assist in the assessment of the response to vasoactive agents. Cytokines, induced by gram-negative organisms, may alter adrenoreceptors in myocardium and vasculature.

Neonatologist-Performed Ultrasound-Guided Internal Jugular Vein Cannulation.

We retrieved data of ultrasound-guided neonatal internal jugular vein (IJV) cannulations done between November, 2020 and March, 2021. Of the 33 ultrasound-guided IJV cannulation in neonates, 32 were successful with overall success rate of 97%. Median (IQR) number of attempts per insertion was 2 (1,3.5). There were no major complications observed during the insertion of the catheter. In one instance, inadvertent carotid artery puncture was encountered, without significant bleeding.

Effects of latent iron deficiency on auditory neural maturation during early infancy in infants above 35 weeks' gestation.

BACKGROUND: Latent iron deficiency (LID) at birth is associated with prolonged latencies in auditory brainstem response (ABR), a surrogate for neural maturation. This study aimed to compare wave and inter-peak latencies of ABR at birth and at 4-6 months of age in infants ≥35 weeks of gestation with normal iron status (NIS) and LID. METHODS: Neonates born at ≥35 weeks were screened. Cord ferritin value ≤ 75 ng/mL and >75 ng/mL were classified as LID and NIS, respectively. ABR was performed within 48 h of birth. The absolute latencies of waves I, III, and V, and inter-peak latencies I-III, III-V, and I-V were computed. Infants were reassessed at 4-6 months of age for hemoglobin, serum ferritin levels, and ABR latencies. RESULTS: In total, 160 neonates were enrolled. The mean (SD) birth weight and gestational age of the study population were 2843 (384) g and 38.3 (1.1) weeks, respectively. Approximately 122 infants completed follow-up until 4-6 months of age: 37 in the LID group and 85 in the NIS group. Overall, the wave and interpeak latencies in both groups at birth were comparable. At 4-6 months, the absolute latencies of waves I, III, and V, and inter-peak latencies I-III, III-V, and I-V were decreased and were comparable in both groups. Among small-for-gestational-age neonates, inter-peak latencies in I-III and I-V at birth were significantly longer in the LID group than in the NIS group. Nine (24.3%) infants in the LID group and none in the NIS group were iron-deficient at 4-6 months of age. CONCLUSION: There was no difference in wave or inter-peak latencies at birth and at 4-6 months of age in neonates aged ≥35 weeks with or without LID. However, infants with LID at birth have a significant risk of iron deficiency at 4-6 months of age. CTRI/2017/08/009379 (www.ctri.nic.in).

Restrictive Threshold for the Management of Patent Ductus Arteriosus in Very Low Birth Weight Neonates.

OBJECTIVE: To compare outcomes of very low birth weight (VLBW) neonates before and after the change in practice for treatment of PDA. METHODS: Medical records of VLBW neonates were reviewed. Neonates were categorized in two groups: Period I (January, 2012 to July, 2015) and Period II (August, 2015 to December, 2016). The primary outcome of study was composite outcome of death or broncho-pulmonary dysplasia (BPD). RESULTS: The composite outcome (Death/BPD) was comparable in two groups; adjusted OR (95% CI) 1.1 (0.6, 1.9). Mortality and severe BPD were also comparable. The pharmacological treatment for PDA was required in 8.4% vs 2.6% of VLBW neonates during Period I and II, respectively (P=0.03). Durations of invasive and noninvasive ventilation were comparable during two periods. CONCLUSIONS: Restrictive threshold for management of PDA in VLBW neonates may not be associated with increase in morbidities or mortality and possibly would reduce need for pharmacological treatment or surgical ligation.

Use of Point of Care Ultrasound for Confirming Central Line Tip Position in Neonates.

OBJECTIVE: To assess feasibility of ultrasound (USG) evaluation of tip position of central catheter in neonates and to determine agreement between radiograph and USG-based assessments. METHODS: This prospective observational study was conducted in a tertiary neonatal intensive care unit from April, 2019 to August, 2019. Point of care USG and radiograph were performed on infants who underwent central line placement. Agreement between the two was determined using Kappa statistics. RESULTS: Of the 141 central catheters insertions performed, USG was performed for 65 central catheters. On USG, catheter tip position could be assessed and defined in 62 (95%) of cases. Of these 62 central lines, 24 (38.7%) were defined as optimally placed on radiograph and 20 (32.2%) were defined as optimally placed on USG. There was excellent agreement between radiographic and USG assessment of catheter tip position [K (95% CI) = 0.86 (0.73-0.99), P <0.001]. All 38 lines found to be mal-positioned on radiograph were assessed as sub-optimal on USG as well. CONCLUSIONS: Point of care USG has excellent agreement with radiography for confirming central line tip position.

Early prediction of feed intolerance in very low birth weight preterm infants using superior mesenteric artery blood flow velocity.

Objective: To evaluate the utility of superior mesenteric artery (SMA) flow velocity post feeding for predicting time to achieve full enteral feeds in very low birth weight (VLBW) neonates.Subjects: In this prospective cohort study preterm VLBW infants were followed until they achieved full enteral feeding.Results: There was no significant difference between prefeed and post feed SMA flow measurements in study subjects. At baseline, it was observed that Small for gestational age (SGA) babies had a significantly lower peak systolic velocity. Time-averaged mean velocity (TAMV) was significantly lower in SGA babies at baseline, 15, 30, 45, and 60 min post feed, but there were no within-group differences noted over time.Conclusion: SMA blood flow velocity measured pre-feed and post-feed times do not correlate with the time to achieve full enteral feeding in very low birth weight neonates. The clinical significance of lower Peak systolic velocity (PSV) and TAMV in SGA infants is unclear.

Early Aggressive Enteral Feeding in Neonates Weighing 750-1250 Grams: A Randomized Controlled Trial.

BACKGROUND: In preterm neonates, enteral feeding is advanced slowly, considering the risk of necrotizing enterocolitis. Prolonged intravenous alimentation in these neonates, however, may increase the risk of sepsis-related morbidity and mortality, particularly in low resource settings. OBJECTIVES: Objective of this was study to evaluate impact of aggressive enteral feeding on mortality and morbidities among preterm neonates. DESIGN: Randomized controlled trial. PARTICIPANTS: Neonates with birthweight 750-1250 g. INTERVENTIONS: 131 preterm neonates with birth weight 750-1250 g, admitted to neonatal intensive care unit between April 2012 and June 2014, were randomized to aggressive feeding or conservative feeding regimen. OUTCOMES: The primary outcome of the study was all-cause mortality during hospital stay. The secondary outcomes included proportion of sepsis (blood culture proven), necrotizing enterocolitis, feed intolerance, survival without major morbidity at discharge, time to reach full enteral feed (180 mL/kg/d), duration of hospitalization, and average daily weight gain (g/kg). RESULTS: All-cause mortality was 33.3% in aggressive regimen and 43.1% in conservative regimen, [RR (95%) CI 0.77 (0.49, 1.20)]. Neonates with aggressive feeding regimen reached full enteral feed earlier; median (IQR) 7 (6, 8) days compared to conservative regimen, 10 (9, 14) days; P <0.001. There was no difference in culture positive sepsis rate, survival without major morbidities, feed intolerance, necrotizing enterocolitis, duration of hospitalization and average daily weight gain. CONCLUSIONS: In neonates with birth weight 750-1250 g, early aggressive feeding regimen is feasible but not associated with significant reduction in all-cause mortality, culture positive sepsis or survival without major morbidities during hospital stay. Neonates with aggressive regimen have fewer days on IV fluids and reach full feed earlier.

Human Milk Fortification in India.

Human milk fortification in preterm babies has become a standard of care in developed countries. Use of human milk fortifier (HMF) in very-low-birthweight infants is not a routine practice in India. There are concerns about high osmolality, feed intolerance, necrotizing enterocolitis, risk of contamination and added cost associated with use of HMF. There are limited data from India which address the issue of safety and short-term benefits of human milk fortification. This chapter highlights the issues related to human milk fortification in our country.

T-piece or self inflating bag for positive pressure ventilation during delivery room resuscitation: an RCT.

OBJECTIVE: To compare the duration of positive pressure ventilation (PPV) during delivery room resuscitation in neonates resuscitated with self-inflating bag (SIB) and T-piece resuscitator (TPR). DESIGN: Randomized control trial. SETTING: Delivery room and neonatal intensive care unit of a tertiary care center in northern India. PATIENTS: Consecutively born neonates more than 26 weeks of gestation requiring PPV at birth. INTERVENTION: Eligible neonates were randomized to two groups, SIB and TPR. OUTCOME MEASURES: Duration of PPV, intubation rates in delivery room, incidence of respiratory distress, need for mechanical ventilation during first 48h and its duration, need for surfactant replacement therapy and mortality during NICU stay. RESULTS: Fifty neonates received PPV with a SIB and 40 received PPV with a TPR. The mean (SD) birth weight and gestational age of neonates in SIB and TPR groups were 2264 (872) and 2065 (814)g; 35.1 (3.6) and 34.3 (3.7) weeks, respectively. The median (IQR) duration of PPV in delivery room was significantly less in TPR group as compared to SIB; 30 (30-60)s vs. 60 (30-90)s, respectively; (p<0.001). A higher proportion of neonates required delivery room intubation in SIB group as compared to TPR group (34% vs. 15%, p=0.04). In the TPR group, a higher proportion of neonates could be resuscitated with room air only (72.5% vs. 38%, p=0.001). Other outcomes were comparable in the two groups. Similar findings were observed in neonates <34 weeks, except that fewer neonates resuscitated with TPR required invasive ventilation (31.6% vs. 77.8%, p=0.008). CONCLUSION: Use of TPR during delivery room resuscitation resulted in shorter duration of PPV and lesser rates of intubation as compared to SIB. More infants in this group could be resuscitated with room air only (CTRI/2010/091/002946).

Abdominal circumference or gastric residual volume as measure of feed intolerance in VLBW infants.

BACKGROUND: The aim of the study was to compare prefeed abdominal circumference (AC) and gastric residual volume (GRV) as a measure of feed intolerance in very-low-birth-weight infants (VLBW). METHODS: Eighty VLBW infants were randomized to 2 groups; feed intolerance was monitored by measuring either GRV group or prefeed AC group. The primary outcome was time to full enteral feeds (180 mL · kg · day). Other main outcome measures were feed interruption days, duration of parenteral nutrition, incidence of culture positive sepsis, necrotizing enterocolitis, mortality, and duration of hospital stay. RESULTS: The median (interquartile range) time to achieve full feeds was 10 (9-13) versus 14 (12-17.5) days in AC and GRV groups, respectively (P < 0.001). Infants in AC group had fewer feed interruption days (0 [0-2] vs 2.0 [1, 5], P < 0.001) and shorter duration of parenteral nutrition (P < 0.001). The incidence of culture-positive sepsis in AC and GRV groups was 17.5% and 30 %, respectively (P = 0.18). Duration of hospital stay and mortality were comparable in both the groups. CONCLUSIONS: Prefeed AC as a measure of feed intolerance in VLBW infants may shorten the time taken to achieve full feeds.

Anti-HIV-1 activity, protease inhibition and safety profile of extracts prepared from Rhus parviflora.

BACKGROUND: In the present study, extracts prepared from the leaves of Rhus parviflora Roxb. (Anacardiaceae) were evaluated for their anti-HIV activity, which have been traditionally used for the treatment of neurological disorders such as anxiety, insomnia and epilepsy. METHODS: Aqueous and 50% ethanolic extracts prepared from leaves of the plant were tested for their cytotoxicity and anti-HIV property using reporter gene based assays as well as human peripheral blood lymphocytes (PBLs). Further these extracts were evaluated for their ability to inhibit HIV-1 reverse transcriptase (RT) and protease activity. Safety profile of the extracts was determined on viability of Lactobacillus sp., secretion of pro-inflammatory cytokines by vaginal keratinocytes and transepithelial resistance. RESULTS: Both aqueous (IC50 = 15 µg/ml) and 50% ethanolic (IC50 = 26 µg/ml) extracts prepared from leaves of R. parviflora showed anti-HIV activity in TZM-bl cells wherein the virus was treated with the extracts prior to infection. Further, both the extracts also inhibited virus load in HIV infected CEM-GFP cells and human PBLs. The anti-HIV activity is mediated through inhibition of HIV-1 protease activity. Both the extracts did not disturb the integrity of monolayer formed by intestinal epithelial Caco-2 cells. The extracts when tested up to 100 µg/ml did not significantly reduce the viability of L. plantarum, L. fermentum, L. rhamnosus and L. casei. The extracts (100 µg/ml) did not reveal any cytotoxic effect on vaginal keratinocytes (Vk2/E6E7). Levels of pro-inflammatory cytokines secreted by Vk2/E6E7 cells treated with both the plant extracts were within the non-inflammatory range. CONCLUSIONS: The studies reported herein showed in vitro anti-HIV activity and preliminary safety profile of the extracts prepared from the leaves of R. parviflora.

Ellagic acid & gallic acid from Lagerstroemia speciosa L. inhibit HIV-1 infection through inhibition of HIV-1 protease & reverse transcriptase activity.

BACKGROUND & OBJECTIVES: Banaba (Lagerstroemia speciosa L.) extracts have been used as traditional medicines and are effective in controlling diabetes and obesity. The aim of this study was to evaluate the anti-HIV property of the extracts prepared from the leaves and stems of banaba, and further purification and characterization of the active components. METHODS: Aqueous and 50 per cent ethanolic extracts were prepared from leaves and stems of banaba and were evaluated for cytotoxicity and anti-HIV activity using in vitro reporter gene based assays. Further, three compounds were isolated from the 50 per cent ethanolic extract of banaba leaves using silica gel column chromatography and characterization done by HPLC, NMR and MS analysis. To delineate the mode of action of the active compounds, reverse transcriptase assay and protease assay were performed using commercially available kits. RESULTS: All the extracts showed a dose dependent inhibition of HIV-1-infection in TZM-bl and CEM-GFP cell lines with a maximum from the 50 per cent ethanolic extract from leaves (IC 50 = 1 to 25 µg/ml). This observation was confirmed by the virus load (p24) estimation in infected CEM-GFP cells when treated with the extracts. Gallic acid showed an inhibition in reverse transcriptase whereas ellagic acid inhibited the HIV-1 protease activity. INTERPRETATION & CONCLUSIONS: The present study shows a novel anti-HIV activity of banaba. The active components responsible for anti-HIV activity were gallic acid and ellagic acid, through inhibition of reverse transcriptase and HIV protease, respectively and hence could be regarded as promising candidates for the development of topical anti-HIV-1 agents.

50 years of neonatology in India, progress and future.

India has made impressive gains in its child survival indices during the past half a century with infant mortality rates declining from 159.3 in 1960 to 44 in 2011 and neonatal mortality rate declining from 47 (1990) to 32 (2010). Neonatal health is now an integral part of the countrys flagship program; National Rural Health Mission. Facility based newborn care is not only available in large public and private sectors hospitals, but also in about 300 of Indias district hospitals. Complementing these efforts is home based newborn care being delivered by community health volunteers. The last two decades has also witnessed an increase in newborn research and its incorporation into medical and paramedical education as a major course component. Neonatology now is an independent super-specialty in India. The National Neonatology Forum has had a major role in spearheading reforms in neonatal care in India.

Extracts from Acacia catechu suppress HIV-1 replication by inhibiting the activities of the viral protease and Tat.

BACKGROUND: Acacia catechu (Mimosa family) stem bark extracts have been used traditionally as a dietary supplement as well as a folk medicine given its reported anti-inflammatory, immunomodulatory, hepatoprotective, antioxidant, anti-microbial and anti-tumor activities. The present study was undertaken to evaluate the anti-HIV-1 activity of the extracts from stem bark of A. catechu. METHODS: The aqueous and 50% ethanolic extracts of A. catechu stem bark were prepared and 50% ethanolic extract was further fractioned by successively partitioning with petroleum ether, chloroform and n-butanol. All the extracts and fractions were evaluated for cytotoxicity and anti-HIV-1 activity using different in vitro assays. The active n-butanol fraction was evaluated for its inhibition against HIV-1 reverse transcriptase, integrase, protease, pro-viral genome integration and viral Tat protein mediated transactivation. The effect of n-butanol fraction on the induction of pro-inflammatory cytokines secretion in Vk2/E6E7 cells and transepithelial resistance in Caco-2 and HEC-1A cells was investigated. RESULTS: The aqueous and 50% ethanolic extracts of A. catechu showed IC50 values of 1.8 ± 0.18 µg/ml and 3.6 ± 0.31 µg/ml, respectively in cell-free virus based assay using TZM-bl cells and HIV-1NL4.3 (X-4 tropic). In the above assay, n-butanol fraction exhibited anti-HIV-1 activity with an IC50 of 1.7 ± 0.12 µg/ml. The n-butanol fraction showed a dose-dependent inhibition against HIV-1NL4.3 infection of the peripheral blood lymphocytes and against HIV-1BaL(R-5-tropic) as well as two different primary viral isolates of HIV-1 infection of TZM-bl cells. The n-butanol fraction demonstrates a potent inhibitory activity against the viral protease (IC50 = 12.9 µg/ml), but not reverse transcriptase or integrase. Further, in Alu-PCR no effect on viral integration was observed. The n-butanol fraction interfered with the Tat-mediated Long Terminal Repeat transactivation in TZM-bl cells, mRNA quantitation (qRT-PCR) and electrophoretic mobility shift assay (EMSA). The n-butanol fraction did not cause an enhanced secretion of pro-inflammatory cytokines in Vk2/E6E7 cells. Additionally, no adverse effects were observed to the monolayer formed by the Caco-2 and HEC-1A epithelial cells. CONCLUSIONS: The results presented here show a potential anti-HIV-1 activity of A. catechu mediated by the inhibition of the functions of the viral protein and Tat.

Neural tube defect repair and ventriculoperitoneal shunting: indications and outcome.

Neural tube defect with its global involvement of nervous system has lot of implications. There is cotroversy in terms of timing of repair, simultaneous or metachronous ventriculoperitoneal shunt and criteria for shunt surgery in neonatal age. We are reporting our approach and results of management of this disease in neonatal period.