Very Low Birth Weight Neonates Research Articles

Necrotising enterocolitis in a middle-income country: Early onset and risk factors for mortality.

There is limited literature available about necrotising enterocolitis (NEC) in low- and middle-income countries. This study sought to determine the proportion, pattern and risk factors for mortality among very low birth weight (VLBW) neonates with NEC in a middle-income setting. A retrospective observational cohort study was conducted on all infants with birth weights less than 1501 g admitted from 2018 to 2020 at Groote Schuur Hospital, Cape Town, South Africa. Data were obtained from the Vermont Oxford Network and hospital folders. A total of 104/1582 (6.6%) neonates were diagnosed with NEC with a median onset of 8 days of life. The mortality rate was 39.0%, compared to the all-cause mortality rate of 18.7% for VLBW neonates. Thirty-two (32.0%) neonates with NEC were transferred for surgery of whom 10 (31.3%) died. Small for gestational age (p = 0.13), NEC stage 2B or above (p = 0,002), a positive blood culture (p = 0.018), a raised C-reactive protein (p = 0.013), hyponatraemia (p = 0.004), anaemia requiring blood transfusion (p = 0.003) and thrombocytopenia requiring platelet transfusion (p = 0.033) were associated with mortality. A positive blood culture was found in 37.0% with a predominance of Klebsiella pneumoniae isolates. NEC has an early onset and a high mortality rate in our setting.

Effects of hypertensive disorders of pregnancy on the complications in very low birth weight neonates

ABSTRACT Objective This study was designed to investigate the effects of hypertensive disorders of pregnancy (HDP) on the complications in very low birth weight (VLBW) neonates. Methods We retrospectively included VLBW neonates (<37 weeks) who were delivered by HDP pregnant women with a body weight of < 1,500 g (HDP group) hospitalized in our hospital between January 2016 and July 2021. Gestational age matched VLBW neonates delivered by pregnant women with a normal blood pressure, with a proportion of 1:1 to the HDP group in number, served as normal control. Results Then we compared the peripartum data and major complications between HDP group and control. The body weight, prelabor rupture of membrane (PROM), maternal age, cesarean section rate, fetal distress, small for gestational age (SGA), mechanical ventilation, RDS, necrotizing enterocolitis (NEC) (≥2 stage), Apgar score at 1 min, and mortality in HDP group showed statistical differences compared with those of the control (all p < 0.05). To compare the major complications among HDP subgroups, we classified the VLBW neonates of the HDP group into three subgroups including gestational hypertension group (n = 72), pre-eclampsia (PE) group (n = 222), and eclampsia group (n = 14), which showed significant differences in the fetal distress, Apgar score at 1 min, SGA, ventilation, RDS and NEC (≥2 stage) among these subgroups (all p < 0.05). Multivariate regression analysis showed that eclampsia and PE were the independent risk factors for SGA and NEC, respectively. Conclusion HDP was associated with increased incidence of neonatal asphyxia, fatal distress, SGA, mechanical ventilation, RDS, NEC and mortality. Besides, eclampsia and PE were independent risk factors for SGA and NEC.

Predictors of Mortality in Very Low Birth Weight Neonates With Congenital Diaphragmatic Hernia

BackgroundLimited data exists regarding the mortality of very low birth weight (VLBW) neonates with congenital diaphragmatic hernia (CDH). This study aims to quantify and determine predictors of mortality in VLBW neonates with CDH. MethodsThis analysis of 829 U.S. NICUs included VLBW [birth weight ≤1500g] neonates, born 2011–2021 with and without CDH. The primary outcome was in-hospital mortality. A generalized estimating equation regression model determined the adjusted risk ratio (ARR) of mortality. ResultsOf 426,140 VLBW neonates, 535 had CDH. In neonates with CDH, 48.4% had an additional congenital anomaly vs 5.5% without. In-hospital mortality for neonates with CDH was 70.4% vs 12.6% without. Of those with CDH, 73.3% died by day of life 3. Of VLBW neonates with CDH, 38% were repaired. A subgroup analysis was performed on 60% of VLBW neonates who underwent delivery room intubation or mechanical ventilation, as an indicator of active treatment. Mortality in this group was 62.7% for neonates with CDH vs 16.4% without. Higher Apgars at 1 min and repair of CDH were associated with lower mortality (ARR 0.91; 95%CI 0.87,0.96 and ARR 0.28; 0.21,0.39). The presence of additional congenital anomalies was associated with higher mortality (ARR 1.14; 1.01,1.30). ConclusionThese benchmark data reveal that VLBW neonates with CDH have an extremely high mortality. Almost half of the cohort have an additional congenital anomaly which significantly increases the risk of death. This study may be utilized by providers and families to better understand the guarded prognosis of VLBW neonates with CDH. Type of StudyLevel II. Level of EvidenceLevel II.

Neonatal Birthweight Spectrum: Maternal Risk Factors and Pregnancy Outcomes in Saudi Arabia.

Background and Objectives: Low-birth-weight (LBW) neonates are at increased risk of morbidity and mortality which are inversely proportional to birth weight, while macrosomic babies are at risk of birth injuries and other related complications. Many maternal risk factors were associated with the extremes of birthweight. The objectives of this study are to investigate maternal risk factors for low and high birthweight and to report on the neonatal complications associated with abnormal birth weights. Materials and Methods: We conducted a retrospective analysis of medical records of deliveries ≥ 23 weeks. We classified the included participants according to birth weight into normal birth weight (NBW), LBW, very LBW (VLBW), and macrosomia. The following maternal risk factors were included, mother's age, parity, maternal body mass index (BMI), maternal diabetes, and hypertension. The neonatal outcomes were APGAR scores < 7, admission to neonatal intensive care unit (NICU), respiratory distress (RD), and hyperbilirubinemia. Data were analyzed using SAS Studio, multivariable logistic regression analyses were used to investigate the independent effect of maternal risk factors on birthweight categories and results were reported as an adjusted odds ratio (aOR) and 95% Confidence Interval (CI). Results: A total of 1855 were included in the study. There were 1638 neonates (88.3%) with NBW, 153 (8.2%) with LBW, 27 (1.5%) with VLBW, and 37 (2.0%) with macrosomia. LBW was associated with maternal hypertension (aOR = 3.5, 95% CI = 1.62-7.63), while increasing gestational age was less likely associated with LBW (aOR = 0.51, 95% CI = 0.46-0.57). Macrosomia was associated with maternal diabetes (aOR = 3.75, 95% CI = 1.67-8.41), in addition to maternal obesity (aOR = 3.18, 95% CI = 1.24-8.14). The odds of VLBW were reduced significantly with increasing gestational age (aOR = 0.41, 95% CI = 0.32-0.53). In total, 81.5% of VLBW neonates were admitted to the NICU, compared to 47.7% of LBW and 21.6% of those with macrosomia. RD was diagnosed in 59.3% of VLBW neonates, in 23% of LBW, in 2.7% of macrosomic and in 3% of normal-weight neonates. Hyperbilirubinemia was reported in 37.04%, 34.21%, 22.26%, and 18.92% of VLBW, LBW, NBW, and macrosomic newborns, respectively. Conclusions: Most neonates in this study had normal birthweights. Maternal hypertension and lower gestational age were associated with increased risk of LBW. Additionally, maternal obesity and diabetes increased the risk of macrosomia. Neonatal complications were predominantly concentrated in the LBW and VLBW, with a rising gradient as birthweight decreased. The main complications included respiratory distress and NICU admissions.

Exploring Pregnant Women and Very Low Birth Weight Babies: A Study in a Tertiary Care Medical College Hospital

Low birth weight is a critical indicator of new-born health, particularly in developing countries where it is moreprevalent. However, data on low birth weight in these countries is often limited due to home or small healthfacility deliveries that go unreported. This study aimed to examine the characteristics of mothers and their verylow birth weight (VLBW) infants, who are at high risk for morbidity and mortality.Methods: The study included hospitalized mothers and their VLBW neonates. Pre- and perinatal data, includinghospitalization complications, were collected from case files using a pre-designed questionnaire and analysed.Results: The mean maternal age in the study group was 24.88 ± 2.92 years, with the majority falling between 21 and25 years. Gestational hypertension, alone or in combination with other risk factors, was the most significant riskfactor (18.36%). The caesarean section (C-section) rate was 58.7%. Among the study group, 49.81% of mothers hadone or more risk factors, with gestational hypertension (18.3%), leaking (12.6%), eclampsia (1.3%), and gestationaldiabetes mellitus (4.8%) being the most prevalent. Out of 7,288 neonates born in SMGS Hospital, 458 (4.3%) wereVLBW babies, with a mean gestational age of 32.19 ± 1.5 weeks and a mean birth weight of 1320 ± 0.21 grams. Themortality rate among VLBW neonates was 5.8%. The most common neonatal outcomes were sepsis (21.8%) andrespiratory distress syndrome (15.9%). The need for mechanical ventilation and surfactant therapy was 6.5% and9.1%, respectively.Conclusion: Delivering preterm VLBW babies from mothers with high-risk factors in hospitals equipped withtertiary care neonatal intensive care units is crucial to improving their outcomes and survival. These findingshighlight the importance of appropriate healthcare facilities for this vulnerable population.

Short-Term Outcomes of Early Oral Colostrum Administration in VLBW Neonates: An Open-Label Randomized Controlled Trial.

Oropharyngeal colostrum priming (OCP) has been proposed as a potential nutritional option for very low birth weight (VLBW) newborns. This study aimed to determine short-term outcomes of early oral colostrum administration in VLBW neonates. This open-label randomized controlled trial was conducted on VLBW neonates admitted to Mahdieh Hospital, Tehran, Iran, between February and December 2022. According to the protocol, all eligible neonates were randomized evenly to the intervention group, which received oral colostrum (OC), and the control group, which received no OC. Finally, short-term outcomes of early OC administration were compared between groups using the independent-samples t test, chi-square, and Fisher exact tests. Of 80 randomized neonates, 37 and 39 from the intervention and control groups entered the final analysis, respectively. Neonates in the intervention and control groups did not significantly differ in terms of peripherally inserted central catheter (PICC) infection (P = 0.728), sepsis (P = 0.904), necrotizing enterocolitis (NEC) (P > 0.999), intraventricular hemorrhage (IVH) (P = 0.141), retinopathy of prematurity (ROP) (P = 0.923), and bronchopulmonary dysplasia (BPD) (P = 0.633). Furthermore, there was no significant difference between groups considering the time to reach 120 cc/kg feeds (P = 0.557), time to reach birth weight (P = 0.157), length of hospitalization (P = 0.532), and mortality rate (P = 0.628). The results of our study revealed that despite safety, early OC administration did not improve any of the short-term outcomes in VLBW neonates.

Mortality Risk Assessment by SNAP-II and SNAPPE-II among Very Low Birth Weight Newborns- An Observational Study

Introduction: Very Low Birth Weight (VLBW) babies are those with a birth weight of less than 1500 gm and require special care, attention, and resources. However, despite all efforts, their mortality rate remains high. Proper assessment of these neonates is crucial to identify high-risk cases and take early steps to reduce mortality. In addition to technical advances in neonatal care, severity scores have been developed to predict neonatal mortality. Richardson developed the Score for Neonatal Acute Physiology (SNAP-II) and SNAP with Perinatal Extension (SNAPPE-II) as scoring systems for predicting mortality in the Neonatal Intensive Care Unit (NICU). Aim: To assess the usefulness of SNAP-II and SNAPPE-II as predictors of mortality in VLBW neonates. Materials and Methods: This was an observational cross-sectional study involving 145 VLBW neonates admitted to the NICU of North Bengal Medical College and Hospital (NBMCH) from May 2019 to April 2020. Relevant data were collected to assess the mortality risk scores SNAP-II and SNAPPE-II. The outcome of discharge or death was recorded. Data entry was performed using MS excel and analysed using Statistical Package for Social Sciences (SPSS) version 20.0. The relationship between newborn survival and SNAP-II or SNAPPE-II final scores was determined using the Mann- Whitney U test, and the relationship between survival and various SNAP-II and SNAPPE-II score categories was determined using Fisher’s-Exact Test. A p-value of less than 0.05 was considered statistically significant. An ROC curve was generated to determine the best cutoff score for predicting mortality. Results: The mean scores of SNAP-II and SNAPPE-II were higher in babies who expired compared to those who survived. The mean (±SD) SNAP-II scores were 8.96 (±13.865) for survived newborns and 41.08 (±23.174) for expired newborns. The mean (±SD) SNAPPE-II scores were 20.01 (±14.54) for survived newborns and 48.85 (±25.02) for expired newborns. The optimal cutoff values for SNAP-II and SNAPPE-II in predicting mortality were 31.5 and 36, respectively. The sensitivity and specificity of SNAP-II were 83.0% and 89.1%, while for SNAPPE-II they were 69.8% and 89.1%, respectively. Conclusion: The mean SNAP-II and SNAPPE-II scores were higher among expired VLBW neonates compared to those who survived. A SNAP-II score of 31.5 and SNAPPE-II score of 36 were associated with higher mortality, indicating that both scores are effective predictors of mortality regardless of Gestational Ages (GA) and birth weight.

Multimodal Sensory Stimulation among Very Low Birth Weight Preterm Newborns: A Quasi-experimental Study at a Tertiary Care Hospital in Agartala, Tripura, India

Introduction: There is a continuous search for an effective intervention to help preterm low birth weight neonates overcome their poor growth and developmental outcomes. Most researchers have examined the effect of Oromotor Stimulation (OMS) on feeding performance. Studies exploring Multimodal Sensory Stimulation (MSS) on various outcome parameters are sparse and reveal inconsistent results. Aim: To analyse the effectiveness of MSS in improving weight gain, length of hospitalisation, and feeding performance in preterm Very Low Birth Weight (VLBW) neonates. Materials and Methods: This quasi-experimental study was conducted between June 2021 and December 2022 in the Paediatrics Department of Agartala Government Medical College, Agartala, Tripura, India. A total of 104 hospitalised neonates with gestational age from 28 to less than 37 weeks and birth weight from 1000 to less than 1500 grams (VLBW) were included in the study. All neonates received standard care and Kangaroo Mother Care (KMC). On the advice of some faculties, several of them also received MSS. All neonates were divided into two groups: those who received MSS and those who did not, and they were monitored until discharge. Mean hospitalisation length, weight gain, and transition time were derived and statistically analysed using Chi-square and Mann-Whitney U tests. Results: In the present study, the mean gestational age was 32.04±1.75 and 32.679±1.19 weeks, and the M:F ratio was 1.43:1 and 1.30:1 in the MSS-given and MSS-not given groups, respectively. Mean weight gain was significantly higher in the MSS-given group (97.00±123.09 g versus- 23.42±43.96 g). Mean hospitalisation length was longer in the MSS-given group, but transition time did not differ significantly across the groups. Conclusion: Multimodal sensory stimulation is effective in promoting weight gain in preterm VLBW neonates.

TO STUDY THE EFFECT OF MATERNAL FACTORS ON MORTALITY OF VERY LOW BIRTH WEIGHT NEONATES

Objectives: The present study is to determine the influences of maternal risk factors on neonatal mortality in very low birth weight (VLBW) infants born in central India. Methods: A nested case–control study was conducted in the prospectively assembled cohort at the Department of Pediatrics Government Medical College and Hospital, Nagpur, India, for 2 years. Intramural neonates admitted to NICU with a birth weight of 500–1500 g were included in the study. Newborns with major congenital malformation and those who died in the delivery room or within 12 h of birth were excluded from the study. Results: A total of 260 inborn VLBW newborns admitted to the NICU were enrolled. The mean gestational age was 33.58±4.8 weeks, and the mean birth weight was 1256.56±182.8 g. The overall case fatality rate was 50.38%. Maternal body mass index (BMI) &lt;18.5 g/m2 (p=0.0019 [(Odds Ratio [OR]=3.23) (95% confidence interval [CI]. 1.43–7.80)]) and ante partum hemorrhage (p=0.0001[(OR=3.57) (95% CI 1.82–7.22)]) were two maternal factors which significantly increased the risk of death. However, antenatal steroid coverage (p=0.0005 [(OR=2.25) (95% CI 1.12–5.35)]) was associated with improved survival of VLBW neonates. Conclusion: It can be said that very low birth neonates, especially those weighing &lt;1000 g, preterm, and who are critically ill due to disturbance in pulmonary and circulatory physiology have a very high risk of mortality. Low maternal BMI and antepartum hemorrhage in mothers of VLBW neonate were associated with increased neonatal mortality and ACS therapy was associated with decreased neonatal mortality.

RISK FACTORS ASSOCIATED WITH PROLONGED MECHANICAL VENTILATION IN VERY LOW BIRTH WEIGHT INFANTS

Introduction. Mechanical ventilation (MV) remains a life-saving intervention for the sickest very low birth weight (VLBW) neonates. Despite the widespread use of non-invasive respiratory support, many VLBW neonates require some duration of MV during their initial hospitalization. As prolonged exposure to MV is associated with adverse outcomes in VLBW infants, it is important to identify the factors that influence the duration of this intervention.The study aimed to determine the factors affecting the duration of MV in VLBW infants.Material and methods. Data from a prospectively created computerized database were used in a retrospective cohort study. The database included information on 1086 VLBW infants &lt; 32 weeks' gestation who were ventilated at any time during their hospitalization at the tertiary care hospital between January 2010 and December 2020. Factors that potentially influenced the duration of MV were examined.The research was carried out in compliance with the requirements of bioethics as part of the planned scientific work of the department (state registration number 0117U001083).The data obtained were analyzed using descriptive and comparative statistics, as well as Spearman's rank correlation coefficient and one-way analysis of covariance (ANCOVA). Measurements with normal distribution are presented as mean (standard deviation). Non-parametric continuous data are presented as median (interquartile range). All values were considered significant when p &lt;0.05.The study was carried out as a part of the planned scientific work of the department "Clinical-laboratory and instrumental substantiation of differential approaches to diagnosis, treatment and prevention of childhood diseases" (state registration number 0122U000164) without external sources of funding.Results. According to univariant analysis, bronchopulmonary dysplasia (BPD) (rS=0.32, p&lt;0.05), severe BPD (rS=0.418, p&lt;0.05), pneumothorax (rS=0.06, p=0.05), severe intraventricular hemorrhages (IVH) (rS=0.255, p&lt;0.05), periventricular leukomalacia (PVL) (rS=0.15, p&lt;0.05), sepsis (rS=0.087, p&lt;0.05), necrotizing enterocolitis (rS=0.088, p&lt;0.05), longer duration of antibiotic therapy (rS=0.168, p&lt;0.05), and a lower gestational age (rS=-0.118, p&lt;0.05) were associated with longer duration of MV in VLBW infants. At the same time, BPD (F=18.544, p&lt;0.0001), severe BPD (F=109.810, p&lt;0.0001), severe IVH (F=23.859, p&lt;0.0001), PVL (F=15.031, p&lt;0.0001), and more days of antibiotic therapy (F=13.173, p&lt;0.0001) significantly and independently affected the duration of MV based on the results of one-way ANCOVA.Conclusion. Severe lung and brain injury and prolonged antibiotic exposure were the main risk factors that significantly and independently prolonged MV in VLBW infants.

Efficacy of peritoneal drainage in very-low-birth-weight neonates with Bell's stage II necrotizing enterocolitis: A single-center retrospective study.

Currently, pediatric surgeons are challenged by a lack of consensus on the optimal management strategy (conservative or surgical) for children with Bell's stage II necrotizing enterocolitis (NEC). To evaluate the clinical efficacy of peritoneal drainage in very-low-birth-weight (VLBW) neonates with modified Bell's stage II NEC. This was a retrospective analysis of 102 NEC (modified Bell's stage II) neonates born with VLBW who were treated at the Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center) between January 2017 and January 2020; these included 24 cases in the peritoneal drainage group, 36 cases in the exploratory laparotomy group, and 42 cases in the conservative treatment group. The general characteristics were comparable in the three groups (P > 0.05). Compared with conservative treatment, peritoneal drainage was associated with significantly shorter fasting time, abdominal distension relief time, fecal occult blood (OB) negative conversion time, and reduced hospital length of stay (HLOS) (P < 0.05 for all). Despite some advantages of peritoneal drainage over conservative treatment in terms of cure, conversion to laparotomy, intestinal perforation, intestinal stenosis, and abdominal abscess rates, the differences were not statistically significant (P > 0.05). Compared to exploratory laparotomy, the fecal OB negative conversion time was significantly shorter in the peritoneal drainage group (P < 0.05); similarly, the exploratory laparotomy group showed longer fasting time, abdominal distension relief time, HLOS, and higher complication rate compared to peritoneal drainage group, but the between-group differences were not statistically significant (P > 0.05). Peritoneal drainage, an easy-to-operate procedure, can improve the clinical symptoms of VLBW neonates with Bell's stage II NEC and help reduce the HLOS.

The eNAMPT/TLR4 inflammatory cascade drives the severity of intra-amniotic inflammation in pregnancy and predicts infant outcomes.

Introduction: Intra-amniotic inflammation (IAI) or chorioamnionitis is a common complication of pregnancy producing significant maternal morbidity/mortality, premature birth and neonatal risk of chronic lung diseases such as bronchopulmonary dysplasia (BPD). We examined eNAMPT (extracellular nicotinamide phosphoribosyltransferase), a critical inflammatory DAMP and TLR4 ligand, as a potential therapeutic target to reduce IAI severity and improve adverse fetal/neonatal outcomes. Methods: Blood/tissue samples were examined in: 1) women with histologically-proven chorioamnionitis, 2) very low birth weight (VLBW) neonates, and 3) a preclinical murine pregnancy model of IAI. Groups of pregnant IAI-exposed mice and pups were treated with an eNAMPT-neutralizing mAb. Results: Human placentas from women with histologically-proven chorioamnionitis exhibited dramatic NAMPT expression compared to placentas without chorioamnionitis. Increased NAMPT expression in whole blood from VLBW neonates (day 5) significantly predicted BPD development. Compared to untreated LPS-challenged murine dams (gestational day 15), pups born to eNAMPT mAb-treated dams (gestational days 15/16) exhibited a > 3-fold improved survival, reduced neonate lung eNAMPT/cytokine levels, and reduced development and severity of BPD and pulmonary hypertension (PH) following postnatal exposure to 100% hyperoxia days 1-14. Genome-wide gene expression studies of maternal uterine and neonatal cardiac tissues corroborated eNAMPT mAb-induced reductions in inflammatory pathway genes. Discussion: The eNAMPT/TLR4 inflammatory pathway is a highly druggable contributor to IAI pathobiology during pregnancy with the eNAMPT-neutralizing mAb a novel therapeutic strategy to decrease premature delivery and improve short- and long-term neonatal outcomes. eNAMPT blood expression is a potential biomarker for early prediction of chronic lung disease among premature neonates.

Long Duration of Oral Care Using Mother's Own Milk Influences Oral Microbiota and Clinical Outcomes in Very-low-birthweight Infants: Randomized Controlled Trial.

Several studies have focused on the clinical outcomes of oral care using colostrum for a limited time (2-5 days) in very-low-birthweight (VLBW) infants. However, the effect of long-term mother's own milk (MOM) on the clinical outcomes and oral microbiota of VLBW infants remains unknown. In this randomized controlled trial, VLBW neonates were randomly assigned to oral care by MOM or sterile water (SW) groups until they started oral feeding. The primary outcome was oral microbiota composition including alpha and beta diversity, relative abundance, and linear discriminant analysis effect size (LEfSe). The secondary outcomes were various morbidities and mortality. The baseline characteristics of the two groups did not differ (63 neonates, MOM group, n = 30, oral care 22 days; SW group, n = 33, oral care 27 days). There was no significant difference in alpha and beta diversities between the groups before and after the intervention. The MOM group had a significantly lower rate of clinical sepsis than the SW group (47% vs. 76%, risk ratio = 0.62, 95% CI: 0.40-0.97). The relative abundance of Bifidobacterium bifidum and Faecalibacterium were maintained after MOM care, especially in neonates without clinical sepsis, but decreased after SW care. LEfSe showed that neonates in the MOM and SW groups with clinical sepsis had the highest abundance of Pseudomonas and Gammaproteobacteria, respectively, compared with neonates without sepsis. A longer duration of oral care using MOM in VLBW infants sustains healthy bacteria and decreases the risk of clinical sepsis.

Platelet parameters as biomarker for bronchopulmonary dysplasia in very low birth weight neonates in the first two weeks of life.

The pathogenesis of bronchopulmonary dysplasia (BPD) is attributed to the arrested lung development in premature infants. Studies showed the negative impact of inflammatory markers on the developing lung with higher levels of IL1, 6 and 8. Platelets contribute to the acute phase response of inflammation and are a direct source of IL-1β. We conducted a retrospective data review of all preterm babies with gestational age (GA) <32 weeks admitted to NICU to assess the relationship between platelet parameters in the first 2 weeks of life with the incidence and severity of BPD in very low birth weight (VLBW) neonates. Of 114 screened newborns, 92 were included after exclusion criteria. Of these, 62 (67.3%) developed BPD. Mean platelet count (PC) (P=0.008) and mean platelet mass index (PMI) (P=0.027) were significantly lower and mean platelet volume (MPV) (P=0.016) was significantly higher in the BPD group. The highest difference between groups was observed at 2nd week of life for PC and PMI and at 1st week for MPV. Using multivariate logistic analysis, only PC (P=0.017) showed statistical significance. MPV and PMI showed a positive interaction but did not achieve significance (P=0.066 for both). We concluded that platelet parameters in the first 2 weeks of life were associated with the incidence of BPD in VLBW neonates. PC may also predict the severity of BPD in these infants.

Population pharmacokinetics of vancomycin in very low birth weight neonates.

Vancomycin dosing in very low birth weight (VLBW) neonates is challenging. Compared with the general neonatal population, VLBW neonates are less likely to achieve the vancomycin therapeutic targets. Current dosing recommendations are based on studies of the general neonatal population, as only a very limited number of studies have evaluated vancomycin pharmacokinetics in VLBW neonates. The main aim of this study was to develop a vancomycin population pharmacokinetic model to optimize vancomycin dosing in VLBW neonates. This multicenter study was conducted at six major hospitals in Saudi Arabia. The study included VLBW neonates who received vancomycin and had at least one vancomycin serum trough concentration measurement at a steady state. We developed a pharmacokinetic model and performed Monte Carlo simulations to develop an optimized dosing regimen for VLBW infants. We evaluated two different targets: AUC0-24 of 400-600 or 400-800 µg. h/mL. We also estimated the probability of trough concentrations >15 and 20 µg/mL. In total, we included 236 neonates, 162 in the training dataset, and 74 in the validation dataset. A one-compartment model was used, and the distribution volume was significantly associated only with weight, whereas clearance was significantly associated with weight, postmenstrual age (PMA), and serum creatinine (Scr). We developed dosing regimens for VLBW neonates, considering the probability of achieving vancomycin therapeutic targets, as well as different toxicity thresholds. The dosing regimens were classified according to PMA and Scr. These dosing regimens can be used to optimize the initial dose of vancomycin in VLBW neonates.

DNA methylation patterns at birth predict health outcomes in young adults born very low birthweight

BackgroundIndividuals born very low birthweight (VLBW) are at increased risk of impaired cardiovascular and respiratory function in adulthood. To identify markers to predict future risk for VLBW individuals, we analyzed DNA methylation at birth and at 28 years in the New Zealand (NZ) VLBW cohort (all infants born < 1500 g in NZ in 1986) compared with age-matched, normal birthweight controls. Associations between neonatal methylation and cardiac structure and function (echocardiography), vascular function and respiratory outcomes at age 28 years were documented.ResultsGenomic DNA from archived newborn heel-prick blood (n = 109 VLBW, 51 controls) and from peripheral blood at ~ 28 years (n = 215 VLBW, 96 controls) was analyzed on Illumina Infinium MethylationEPIC 850 K arrays. Following quality assurance and normalization, methylation levels were compared between VLBW cases and controls at both ages by linear regression, with genome-wide significance set to p < 0.05 adjusted for false discovery rate (FDR, Benjamini-Hochberg). In neonates, methylation at over 16,400 CpG methylation sites differed between VLBW cases and controls and the canonical pathway most enriched for these CpGs was Cardiac Hypertrophy Signaling (p = 3.44E−11). The top 20 CpGs that differed most between VLBW cases and controls featured clusters in ARID3A, SPATA33, and PLCH1 and these 3 genes, along with MCF2L, TRBJ2-1 and SRC, led the list of 15,000 differentially methylated regions (DMRs) reaching FDR-adj significance. Fifteen of the 20 top CpGs in the neonate EWAS showed associations between methylation at birth and adult cardiovascular traits (particularly LnRHI). In 28-year-old adults, twelve CpGs differed between VLBW cases and controls at FDR-adjusted significance, including hypermethylation in EBF4 (four CpGs), CFI and UNC119B and hypomethylation at three CpGs in HIF3A and one in KCNQ1. DNA methylation GrimAge scores at 28 years were significantly greater in VLBW cases versus controls and weakly associated with cardiovascular traits. Four CpGs were identified where methylation differed between VLBW cases and controls in both neonates and adults, three reversing directions with age (two CpGs in EBF4, one in SNAI1 were hypomethylated in neonates, hypermethylated in adults). Of these, cg16426670 in EBF4 at birth showed associations with several cardiovascular traits in adults.ConclusionsThese findings suggest that methylation patterns in VLBW neonates may be informative about future adult cardiovascular and respiratory outcomes and have value in guiding early preventative care to improve adult health.

Predicting treatment response to vancomycin using bacterial DNA load as a pharmacodynamic marker in premature and very low birth weight neonates: A population PKPD study.

Background: While positive blood cultures are the gold standard for late-onset sepsis (LOS) diagnosis in premature and very low birth weight (VLBW) newborns, these results can take days, and early markers of possible treatment efficacy are lacking. The objective of the present study was to investigate whether the response to vancomycin could be quantified using bacterial DNA loads (BDLs) determined by real-time quantitative polymerase chain reaction (RT-qPCR). Methods: VLBW and premature neonates with suspected LOS were included in a prospective observational study. Serial blood samples were collected to measure BDL and vancomycin concentrations. BDLs were measured with RT-qPCR, whereas vancomycin concentrations were measured by LC-MS/MS. Population pharmacokinetic-pharmacodynamic modeling was performed with NONMEM. Results: Twenty-eight patients with LOS treated with vancomycin were included. A one-compartment model with post-menstrual age (PMA) and weight as covariates was used to describe the time PK profile of vancomycin concentrations. In 16 of these patients, time profiles of BDL could be described with a pharmacodynamic turnover model. The relationship between vancomycin concentration and first-order BDL elimination was described with a linear-effect model. Slope S increased with increasing PMA. In 12 patients, no decrease in BDL over time was observed, which corresponded with clinical non-response. Discussion: BDLs determined through RT-qPCR were adequately described with the developed population PKPD model, and treatment response to vancomycin using BDL in LOS can be assessed as early as 8h after treatment initiation.

Enteral administration of a simulated amniotic fluid in preventing feeding intolerance in very low birthweight neonates: A randomized controlled trial

ObjectivesFeeding intolerance (FI) is a common finding in preterm neonates. Enteral administration of different forms of amniotic fluid (AF) has been tried for treating FI in high-risk neonates. Simulated amniotic fluid (SAF) is a solution with a similar electrolyte composition to human AF. The aim of this study was to examine whether enteral administration of SAF would improve feeding tolerance in very low birthweight (VLBW) neonates. MethodsForty VLBW neonates were randomized to either SAF or placebo (total daily dose 20 mL/kg/d–1 divided every 3 h) to their milk for a maximum of 7 d. Neonates with major congenital anomalies, those in whom early feeding was contraindicated, and those treated with parental erythropoietin and/or human granulocyte stimulating factor were excluded. The primary outcome was the total amount of enteral feeds reached by day 7. Secondary outcomes were incidence of FI and necrotizing enterocolitis (NEC). Study intervention was stopped on completing 7 d, reaching enteral feeds of 100 mL/kg/d–1, or the appearance of any sign of FI or NEC. ResultsAll neonates tolerated the test solution well. The SAF group reached significantly larger volume and higher calories on days 3 and 7 (P < 0.05 for all). No statistical differences were seen between the two groups in incidence of FI (P = 0.311), NEC (P = 0.429), mortality (P = 0.632), length of stay (P = 0.744), or weight gain on day 10 (P = 0.389). Baseline hematologic parameters showed no statistical differences before or after enteral administration (P > 0.05). ConclusionResults of the present study demonstrated that SAF solution might improve feeding tolerance in VLBW babies without evidence of its systemic absorption. Larger multicenter randomized studies are recommended.

Extrauterine Growth Restriction among Very Low Birth Weight Neonate using Intergrowth 21st in a Neonatal Intensive Care Unit: A Retrospective Study

Introduction: Extrauterine growth restriction (EUGR) is a universal problem but its prevalence using recent reference growth charts and morbidities associated with it are lacking. The study aims at estimating EUGR prevalence in very low birth weight (VLBW) neonates and its associated morbidities. Methods: All VLBW neonates admitted to NICU between Jan 2018 to June 2019 were analysed. Neonatal anthropometries were recorded on Intergrowth 21st gender based postnatal growth chart. EUGR was defined by weight below 10th percentile at discharge. Demographic profile and neonatal morbidities were compared between EUGR and non-EUGR by using unpaired t test and Chi-square test. Regression was used for identification of the risk factors. Results: Out of 148 VLBW neonates, 92 (62.1%) were male, 26 (17.56%) were below 1000 gm, 102 (68%) were EUGR at discharge. Mean (SD) birth weight and gestational age were 1202 (221) gms and 30.89 (2.77) wks respectively. Caesarean delivery, higher gestational age, lower birth weight, SGA at birth and prolonged duration to achieve full enteral feeding were significantly associated with EUGR (P &lt; 0.05). Sepsis was significantly associated with EUGR (36.28% vs. 17.4%; P 0.022). EUGR babies needed longer hospital duration (24.56% vs. 16.78%; P 0.005) with a higher mean PMA at discharge (38.07 wks vs. 35.11 wks; P &lt; 0.001). In regression model SGA at birth and delay in achieving full feeding were independent predictor of EUGR. Conclusions: In VLBW neonate, prevalence of EUGR at discharge was 68%. Sepsis was significantly associated with EUGR. SGA and delay in achieving full feeding were independent predictors of EUGR.

Blood products transfusion and retinopathy of prematurity: A cohort study.

The aim of the study was to assess the influence of blood product transfusions on the development and severity of retinopathy of prematurity (ROP). A retrospective cohort study was conducted of very low birth weight (VLBW) newborns with less than 32 weeks gestational age (GA) admitted to the neonatal unit of a tertiary care hospital during the period from 1 January 2008 to 31 December 2021. Data on the degree of ROP and the transfusions received were obtained and analysed. Both univariate and multivariate analyses were performed, by logistic regression. A total of 565 VLBW newborns were recruited, of whom 263 received a red blood cell transfusion prior to 36 weeks corrected GA. The newborns with ROP received significantly more red blood cell transfusions than those not presenting this condition. After adjusting for oxygen therapy and GA, the risk of ROP was found to be 2.77 times higher (95% CI 1.31-5.88) after receiving three or more transfusions, with a 3.95 times higher risk (95% CI 1.40-11.1) of developing severe ROP. Having received the first red blood cell transfusion before 32 weeks corrected GA is associated with an increased risk of ROP (OR 2.18; 95% CI: 1.09-4.36). In VLBW neonates, the number of red blood cell transfusions and their administration before 32 weeks corrected GA are important risk factors for ROP.