Impact of Probiotic Supplementation on duration of hospital stay in Preterm and Low Birth Weight Neonates In a Tertiary Care Centre: A Randomized Controlled Study

Background: Preterm birth (before 37 weeks of gestation) and low birth weight (under 2500 grams) are major contributors to infant mortality worldwide, particularly in developing countries. India alone sees around 12% of births as preterm and 18% as low birth weight, making this a significant public health concern. Aim: To assess the role of probiotics usage on the mortality in preterm and low birth weight neonates in a tertiary care centre- a randomized control study. Methodology: The study involved newborns between 28–36 weeks of gestation or weighing less than 1800 grams, admitted to the NICU at Sharda Hospital and meeting specific inclusion criteria. After obtaining informed consent from parents, data was collected using a structured case form. Participants were randomly assigned to two equal groups (A and B) through a computer-generated block randomization method, with allocation concealed in sealed, numbered envelopes. To ensure objectivity, both the medical team and investigators were blinded to group assignments. The probiotic (Bacillus clausii) and placebo (sterile water) were coded and packed separately, with only the designated nurse aware of which was which. Each baby received 2.5 mL of either the probiotic or placebo orally every 12 hours along with feeds, continued until discharge or death, and paused if feeds were stopped. Results: A total of 112 neonates were enrolled, equally divided into placebo (n=56) and probiotic (n=56). 9 neonates died in placebo group, 1 died in probiotic group and 102 were discharged. Demographics: Gestational age, gender, and birth weight were comparable in both groups. Mortality: Significantly lower in the probiotic group. Conclusion: Based on the findings, the administration of probiotics was associated with reduced mortality rates. Mortality was notably higher in the placebo group compared to the probiotic group

Observations on a cohort of neonates in the preintervention year of the field trial of home-based neonatal care (HBNC) in rural Gadchiroli, India, showed that preterm birth and low birth weight (LBW), <2500 g, constituted the most important risk factors. Owing to a limited access to hospital care, most neonates were managed at home in the subsequent intervention years. The objective of this paper is to evaluate the feasibility and effectiveness of managing LBW and preterm neonates in home setting. We retrospectively analyzed data from the intervention arm (39 villages) in the HBNC trial. Feasibility was assessed by coverage and by quality (19 indicators) of care. Effectiveness was evaluated by change in case fatality (CF) and in the incidence of comorbidities in LBW or preterm neonates by comparing the preintervention year (1995 to 1996) with the intervention years (1996 to 2003). During 1996 to 2003, total 5919 live births occurred in the intervention villages, out of whom 5510 (93%) received HBNC. These included 2015 LBW neonates and 533 preterm neonates, out of whom 97% received only home-based care. The coverage and quality of interventions assessed on 19 indicators was 80.5%. The CF in LBW neonates declined by 58% (from 11.3 to 4.7%, p<0.001), and in preterm neonates, by 69.5% (from 33.3 to 10.2%, p<0.0001). Incidence of the major comorbidities, viz., sepsis, asphyxia, hypothermia and feeding problems, declined significantly. Preterm-LBW neonates without sepsis (270) received only supportive care -- CF in them decreased from 28.2 to 11.5% (p<0.01), and those with sepsis (53) received supportive care and antibiotics -- CF in them decreased from 61 to 13.2% (p<0.005). Supportive care contributed 75% and treatment with antibiotics 25% in the total averted deaths in preterm-LBW neonates. The intrauterine growth restriction (IUGR)-LBW neonates without sepsis (1409) received only supportive care -- the CF was unchanged, and 181 with sepsis received supportive care and antibiotics -- the CF decreased from 18.4 to 8.8% (p<0.05). Treatment with antibiotics explained entire reduction in mortality in IUGR neonates. In total, 55 deaths in LBW neonates were averted by supportive care and 35 by the treatment with antibiotics. Home-based management of LBW and the preterm neonates is feasible and effective. It remarkably improved survival by preventing comorbidities, by supportive care, and by treating infections.

BackgroundDespite recent advances in critical care, infection remains one of the leading causes of mortality and morbidity in the neonatal population. Preterm low birth weight neonates represent the group at...

Background and purpose: Necrotizing enterocolitis is one of the leading causes of morbidity and mortality in neonatal intensive care units particularly in places without neonatal surgical facilities. The best treatment for perforated necrotizing enterocolitis is uncertain. Bedside peritoneal drainage has been used as primary treatment in the management of perforated necrotizing enterocolitis. This study aimed to compare outcomes of bedside peritoneal drainage done by general surgeons as a primary procedure for the treatment of preterm and/or low birth weight neonates with perforated necrotizing enterocolitis to outcomes of early laparotomy performed by pediatric surgeons as regards effectiveness of the procedure as a definitive treatment, the need for delayed laparotomy and mortality rate. Patients and methods: Fifty cases of preterm and/or low birth weight neonates with perforated necrotizing enterocolitis were randomly assigned to one of two groups. Group I was managed by bedside peritoneal drainage done by general surgeon while laparotomy was reserved for non responding cases. Group II was managed by early laparotomy done by pediatric surgeon. Data collected from all cases included birth weight (g), gestational age (weeks), gender, age at operation (bedside peritoneal drainage or early laparotomy). Delayed laparotomy was performed for infants who developed persistent fecal.fistula or suffered late intestinal stricture as well as for closure of enterostomy. Outcomes of bedside peritoneal drainage and early laparotomy were recorded and statistically compared regarding the effectiveness of procedure as a definitive treatment, need for delayed laparotomy and mortality. Results: 16 cases (64%) showed clinical improvement after bedside peritoneal drainage. Bedside peritoneal drainage in Group I and early laparotomy in Group II were effective as a definitive treatment in 10 cases (40%) and 15 cases (60%) respectively. Delayed laparotomy was indicated in 7 cases(28%) in Group I and 8 cases (32%) in Group II.Mortality was recorded in 8 patients (32%) in BPD group and in 9 patients (36%) in laparotomy group. Conclusion: According to this study, outcomes of bedside peritoneal drainage as a primary treatment for low birth weight and/or preterm neonates with perforated necrotizing enterocolitis showed no significant statistical difference as regards the need for delayed laparotomy and mortality rate when compared to the outcomes of early laparotomy as a primary treatment for the same conditions. Bedside peritoneal drainage provides a useful primary procedure for the management of preterm and low birth weight neonates with perforated necrotizing enterocolitis particularly in healthcare facilities without neonatal surgery capacity.

To assess the impact of emollient therapy on gain in weight and length among preterm and low birth weight babies. Randomised controlled trial. Department of Pediatric Medicine, KEMU / Mayo Hospital Lahore, from January till June 2018. Infants with birth weight between 1.5 and 2.5 Kgs or preterm neonates born between 28 and 37 completed weeks of gestation were included in the study. Neonates with genetic syndrome, infection or with a history of admission in NICU due to any reason, were excluded.They were randomly divided into two groups-A and B, by lottery method. Mothers of the neonates in group A were advised massage with sunflower oil; while mothers of the neonates in group B were advised massage without any emollient. Babies were closely followed up and their weight and length were measured at two months of age and were analysed using SPSS version 23.0. For 140 neonates, the mean increase in weight was 489.84 ± 297.48 grams among group-A neonates (emollient therapy group) and it was 373.43 ± 276.31 grams among group-B neonates (p = 0.018). The mean increase in length was 6.5 ± 1.1 cm, among group-A neonates and 4.8 ± 1.3 cm in group-B neonates (p ˂0.001). Conclusion: Massage with emollient therapy leads to significantly more increase in weight and length compared to massage alone, among preterm and low birth weight neonates.Emollient therapy is an effective non-pharmacological intervention for increasing weight and length in low birth weight and preterm neonates. Key Words: Emollient, Massage, Low birth weight, Preterm neonates, Weight, Length.

Background: Sepsis remains a significant cause of morbidity and mortality in preterm and low birth weight (LBW) neonates, especially in low- and middle-income countries (LMICs). Lactoferrin, a glycoprotein present in breast milk with antimicrobial activity, is a low-cost, readily available, and promising intervention currently under investigation. The available literature presents conflicting results on the impact of lactoferrin on the risk of late-onset sepsis (LOS). This study evaluated the effectiveness of two doses of bovine lactoferrin (bLF) supplementation in preventing LOS and necrotizing enterocolitis (NEC) in preterm and LBW neonates in Pakistan. Methods: A three-arm, double-blind, placebo-controlled, randomized clinical trial in the neonatal intensive care unit of Aga Khan University was conducted from July 2019 to August 2020. Preterm (28 to 36+5 weeks gestational age) and low birth weight (≥1000g to &amp;lt; 2500g) neonates who established enteral feeding by 72 hours were eligible. The exclusion criteria included sepsis before randomization, maternal history of chorioamnionitis or group B streptococcus colonization, and congenital anomalies. Enrolled neonates were randomly assigned in a 1:1:1 ratio using a computer-generated random allocation sequence to receive placebo (D-glucose), 150 mg bLF, or 300 mg bLF mixed with breast milk once daily for 28 days. The study staff, parents, and outcome assessors were blinded to the allocation. The primary outcome was late-onset sepsis from the trial entry to 28 days. The secondary outcome was NEC from the trial entry to 28 days. Neonates were followed weekly for 28+2 days, and episodes of LOS and NEC were recorded. Results: Of 305 neonates enrolled, 102, 102, 102, and 101 were randomized to receive a placebo (arm A), 150 mg bLF (arm B), and 300 mg bLF (arm C), respectively. Outcome data of 291 participants (99 in arm A, 95 in arm B, and 97 in arm C) were available for inclusion in the intention-to-treat analysis. The frequency of culture-proven sepsis was 8/102 (7.8%) in arm A compared to 1 /102 (0.98%) (p=0.020) in arm B and 5/101 (4.9%) in arm C (p=0.390). We did not find any difference in episodes of NEC between arms A (n=3, 3%) and B (n=0, 0%) (p=0.087) or between arms A and C (n=2, 2%) (p=0.650). We reported compliance rates of 79 (79.79%) in arm A, 78 (82.1%) in arm B, and 82 (84.53%) in arm C for investigational products. Arm C recorded two deaths, but neither was attributed to the intervention. Conclusions: Bovine lactoferrin supplementation may prevent late-onset sepsis in neonates of preterm and low birth weight. However, further trials with larger sample sizes are required to confirm its efficacy in these at-risk groups.

Background: Sepsis remains a significant cause of morbidity and mortality in preterm and low birth weight (LBW) neonates, especially in low- and middle-income countries (LMICs). Lactoferrin, a glycoprotein present in breast milk with antimicrobial activity, is a low-cost, readily available, and promising intervention currently under investigation. The available literature presents conflicting results on the impact of lactoferrin on the risk of late-onset sepsis (LOS). This study evaluated the effectiveness of two doses of bovine lactoferrin (bLF) supplementation in preventing LOS and necrotizing enterocolitis (NEC) in preterm and LBW neonates in Pakistan. Methods: A three-arm, double-blind, placebo-controlled, randomized clinical trial in the neonatal intensive care unit of Aga Khan University was conducted from July 2019 to August 2020. Preterm (28 to 36 + 5 weeks gestational age) and low birth weight (≥1000 g to <2500 g) neonates who established enteral feeding by 72 h were eligible. The exclusion criteria included sepsis before randomization, maternal history of chorioamnionitis or group B streptococcus colonization, and congenital anomalies. Enrolled neonates were randomly assigned in a 1:1:1 ratio using a computer-generated random allocation sequence to receive placebo (D-glucose), 150 mg bLF, or 300 mg bLF mixed with breast milk once daily for 28 days. The study staff, parents, and outcome assessors were blinded to the allocation. The primary outcome was late-onset sepsis from the trial entry to 28 days. The secondary outcome was NEC from the trial entry to 28 days. Neonates were followed weekly for 28 ± 2 days, and episodes of LOS and NEC were recorded. Results: Of 305 neonates enrolled, 102, 102, and 101, respectively, were randomized to receive a placebo (arm A), 150 mg bLF (arm B), and 300 mg bLF (arm C), respectively. Outcome data of 291 participants (99 in arm A, 95 in arm B, and 97 in arm C) were available for inclusion in the intention-to-treat analysis. The frequency of culture-proven sepsis was 8/102 (7.8%) in arm A compared to 1/102 (0.98%) (p = 0.020) in arm B and 5/101 (4.9%) in arm C (p = 0.390). We did not find any difference in episodes of NEC between arms A (n = 3, 3%) and B (n = 0, 0%) (p = 0.087) or between arms A and C (n = 2, 2%) (p = 0.650). We reported compliance rates of 79 (79.79%) in arm A, 78 (82.1%) in arm B, and 82 (84.53%) in arm C for investigational products. Arm C recorded two deaths, but neither was attributed to the intervention. Conclusions: Bovine lactoferrin supplementation did not prevent late-onset sepsis in neonates of preterm and low birth weight in our trial. However, given the small sample size, further trials with larger sample sizes are required to investigate its efficacy in these at-risk groups.

Necrotizing enterocolitis (NE) is inflammatory disease and its prevalence was increase in preterm and low birth weight (LBW) neonates. This study was aimed to investigate the differences of fecal calprotectin level in breast milk-formula vs formula feeding infants in preterm and low birth weight neonates with necrotizing enterocolitis. There are 32 preterm and LBW neonates with NE were divided into two group (breast milk-formula and formula only feeding group). Fecal calprotectin level was measured using ELISA method. This study showed that fecal calprotectin level in breast milk-formula feeding group was insignificantly lower as compared to formula feeding group (independent t-test, p = 0.503). Further analysis showed that fecal calprotectin level was negatively correlated with patient’s outcome (Spearman correlation test, p = 0.03, r = 0.512). We concluded that fecal calprotectin level in breast milk-formula feeding group was insignificantly lower as compared to formula feeding only group in preterm and low birth weight neonates diagnosed with necrotizing enterocolitis. There was negative correlation between fecal calprotectin level and patient’s outcome.

Major congenital anomalies (MCAs) are significant contributors to perinatal morbidity and mortality, especially in preterm and low birth weight neonates. The association between MCAs, preterm birth, and low birth weight remains poorly defined, necessitating further research to refine management strategies. This study aimed to investigate the impact of MCAs on preterm and low birth weight births in a sample of the Emirati population. The analysis was based on a cohort of singleton live births from the Mutaba’ah study (2017–2023). Regression models assessed the association between MCAs and both preterm birth and low birth weight, adjusting for maternal and neonatal characteristics. Neonates with any MCAs had two-times higher odds of preterm birth (adjusted odds ratio (AOR): 2.0, 95% confidence interval (CI) 1.3–2.9) and low birth weight (AOR: 2.2, 95% CI 1.4–3.3), compared with MCAs-free neonates. Moreover, neonates with multiple MCAs had significantly increased odds of being born preterm (AOR: 5.3, 95% CI 2.6–10.7) or with low birth weight (AOR: 3.5, 95% CI 1.5–8.6). This study provides evidence of a strong association between MCAs and increased risks of preterm birth and low birth weight, highlighting the need for a proactive, multidisciplinary approach to improve health outcomes for this vulnerable population.

Treatment of localized periodontal disease in pregnancy does not reduce the occurrence of preterm birth: results from the Periodontal Infections and Prematurity Study (PIPS)

The treatment of preterm and low birth weight (LBW) neonates born with congenital heart disease (CHD) requiring early cardiac intervention remains challenging. We aimed to analyze morbidity and mortality in this combined high-risk patient group. A retrospective cohort study was conducted of preterm [<37 weeks gestational age (GA)] and/or LBW neonates (<2,500 g) born with a diagnosis of CHD, which requires invasive cardiac intervention (surgery or catheter) within their first year of life. Patients born between 2016 and 2020 and treated in three European pediatric heart centers were included. A total of 308 neonates (51% male) with CHD were included. Of those, 237 (77%) were born preterm, 259 (84%) were LBW, and 188 (61%) were both. The median GA was 35.4 weeks (interquartile range 33.3-36.9) and the mean birth weight was 2,016 ± 580 g. CHD was categorized as simple (12%), moderate (64%), or severe (24%). The overall complication rate was 45% and was highest in patients with severe CHD (p = 0.002). One-year mortality (19%) was associated with severe CHD, low relative birth weight in patients with genetic diagnoses, and low GA at birth, whereas GA at birth significantly impacted survival only after 3 months of life. The high morbidity and mortality in preterm and LBW neonates with CHD reflect their complexity and consequent limited treatment feasibility.

Background: Neonatal mortality is an increasingly important public health issue in developing countries. Low birth weight is the single most important factor affecting neonatal mortality. Globally low birth weight accounts for 10% of neonatal mortality. The purpose of our study was to find out the impact of low birth weight on neonatal mortality and its effect on preterm and small for gestational age babies in a tertiary care center in India. Methods: 173 consecutive, low birth weight neonates weighing less than 2.5 kilograms referred to a tertiary care center over a period of one year were included. Age, gender, gestational age, birth weight, comorbid conditions and clinical outcome were recorded prospectively. Neonates were divided into two groups. 83 preterm low birth weight neonates (<37 weeks of gestation, New Ballard score) and 90 term small for gestational age neonates (<10 th percentile of gestational age, IAP charts). Mortality data was analyzed using SPSS version 11.5 and Chi square test result with P<0.05 was considered as significant. Results: Preterm neonatal mortality was 32.5 percent (27 neonates). Neonatal mortality was 18.9 percent (17 neonates) in term small for gestational age babies. Major causes of death in low birth weight neonates were prematurity and its associated causes (43%) followed by congenital anomalies (34%) and birth asphyxia (14%). Other minor causes include inborn errors of metabolism. Conclusions: Preterms are more susceptible to death compared to small for gestational age babies in a tertiary intensive care unit.

Challenges in defining and classifying the preterm birth syndrome

HIV treatment of neonates requires identifying appropriate antiretroviral dosing regimens. Our aims were to characterize raltegravir elimination kinetics in low birth weight (LBW) neonates after maternal dosing and to develop a pharmacokinetic model to predict raltegravir plasma concentrations for term and preterm neonates. Mothers living with HIV who received raltegravir during pregnancy and their LBW neonates participated in IMPAACT P1097 study. Up to 6 serial plasma samples were collected from each infant over the first 2 postnatal weeks to characterize raltegravir elimination. Safety laboratory evaluations were obtained, and infants were monitored for 6 weeks for signs of raltegravir toxicity. An integrated maternal-neonatal pharmacokinetic model was developed to predict neonatal raltegravir plasma concentrations. Sixteen mothers and their 18 LBW neonates were enrolled. The median (range) raltegravir elimination half-life was 24.4 (10.1-83) hours (N = 17 neonates). No adverse events related to raltegravir in utero exposure were observed. Pharmacokinetic modeling revealed that raltegravir clearance in full-term LBW neonates was well described by allometric scaling but clearance in preterm LBW neonates was better described using slower clearance maturation kinetics. Simulations suggest receipt of the current dosing recommendations in a 34-week gestation neonate would result in plasma concentrations up to 2.5-fold higher than those observed in full-term LBW infants. Modeling suggests that prematurity reduces raltegravir clearance and a modified raltegravir dosing regimen will be necessary to avoid elevated plasma raltegravir concentrations.

Necrotizing enterocolitis (NEC) is the most common emergency involving the gastrointestinal tract occurring in the neonatal period. There have been published reports that suggest that oral immunoglobulins (Ig)A and IgG produce an immunoprotective effect in the gastrointestinal mucosa. To determine the effect of oral immunoglobulin on the incidence of necrotizing enterocolitis and other complications in preterm or low birth weight (or both) neonates. We used the standard search strategy of the Cochrane Neonatal Group. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2016, Issue 1), PubMed (1966 to January 2016), CINAHL (1982 to January 2016) and EMBASE (1980 to January 2016) and conference proceedings. All randomized or quasi-randomised controlled trials where oral immunoglobulins were used as prophylaxis against NEC in preterm (less than 37 weeks' gestation) or low birth weight (less than 2500 gram), or both, neonates. We performed data collection and analysis in accordance with the standard methods of the Cochrane Neonatal Review Group. The search identified five studies on oral immunoglobulin for the prevention of NEC of which three met the inclusion criteria. In this review of the three eligible trials (including 2095 neonates), the oral administration of IgG or an IgG/IgA combination did not result in a significant reduction in the incidence of definite NEC (typical risk ratio (RR) 0.84, 95% confidence interval (CI) 0.57 to 1.25; typical risk difference (RD) -0.01, 95% CI -0.03 to 0.01; 3 studies, 1840 infants), suspected NEC (RR 0.84, 95% CI 0.49 to 1.46; RD -0.01, 95% CI -0.02 to 0.01; 1 study, 1529 infants), need for surgery (typical RR 0.21, 95% CI 0.02 to 1.75; typical RD -0.03, 95% CI -0.06 to 0.00; 2 studies, 311 infants) or death from NEC (typical RR 1.10, 95% CI 0.47 to 2.59; typical RD 0.00, 95% CI -0.01 to 0.01; 3 studies, 1840 infants). Based on the available trials, the evidence does not support the administration of oral immunoglobulin for the prevention of NEC. There are no randomized controlled trials of oral IgA alone for the prevention of NEC.