Term Neonates Research Articles

Term Neonate With Right-Sided Limb Swelling: A Potpourri of Etiology and Complication.

Term Neonate With Right-Sided Limb Swelling: A Potpourri of Etiology and Complication.

Evaluation of Glymphatic System Development in Neonatal Brain via Diffusion Analysis along the Perivascular Space Index.

Glymphatic system is a recently discovered macroscopic waste clearance system associated with numerous neurological diseases. However, little is known about glymphatic system development in neonates. We sought to evaluate diffusion along the perivascular space (ALPS) index, a proxy for glymphatic system function, in neonates and investigate its potential associations with maturation, sex, and preterm birth. Diffusion magnetic resonance imaging (MRI) data in 418 neonates, including 92 preterm neonates (57 males) and 326 term neonates (175 males), from the Developing Human Connectome Project were used for evaluating ALPS index. Linear regression modeling was performed to assess group differences in the ALPS index according to preterm birth and sex. Pearson's and partial correlation analysis were performed to assess the association between the ALPS index and gestational age (GA) as well as postmenstrual age (PMA) at MRI. Moderation analysis was performed to assess the moderation effect of preterm birth on the relationship between the ALPS index and PMA. Compared to term neonates, preterm neonates exhibited lower ALPS indices (p < 0.001). The ALPS index positively correlated with PMA (p = 0.004) and GA (p < 0.001). Preterm birth (p = 0.013) had a significant moderation effect on the relationship between the ALPS index and PMA. Sex had no significant direct effect (p = 0.639) or moderation effect (p = 0.333) on ALPS index. Glymphatic system development is a dynamic process in neonates, which can be moderated by preterm birth, the ALPS index could serve as a sensitive biomarker for monitoring this process. ANN NEUROL 2024;96:970-980.

Term Neonate With Macrosomia and Coarse Facies: An Overlapping Etiology of Fetal Overgrowth.

Term Neonate With Macrosomia and Coarse Facies: An Overlapping Etiology of Fetal Overgrowth.

Oral sildenafil versus bosentan for treatment of persistent pulmonary hypertension of the newborn: a randomized controlled trial

BackgroundAccess to inhaled nitric oxide (iNO) is limited in low resource settings due to non-availability and high cost. There is a need for research on low-cost alternative therapies for management of persistent pulmonary hypertension of the newborn (PPHN). We aimed to compare oral sildenafil and bosentan as monotherapy in the treatment of neonates with PPHN.Study designIn this single-centre open-label randomized controlled trial (RCT), term and late preterm neonates with PPHN, defined as pulmonary arterial systolic pressure (PASP) > 35 mmHg and requiring fraction of inspired oxygen (FiO2) > 0.21, were randomized to receive oral sildenafil and bosentan. The primary outcome was reduction of PASP by 25% within 48 h after start of drug.ResultsThirty-six neonates were analyzed (18 in each group). Initial PASPs were similar in both groups. The median (IQR) time for the primary outcome (PASP to reduce by 25% within 48 h) was 36 (24–48) h and 96 (48–120) h in sildenafil and bosentan groups respectively (p = 0.008). There was also a higher need to add other pulmonary vasodilators in bosentan group as compared to sildenafil group (p = 0.006).ConclusionSildenafil was associated with quicker reduction of PASP and FiO2 in neonates with PPHN, as compared to bosentan. Large multicentre blinded trials to assess efficacy and safety of bosentan in comparison with other pulmonary vasodilators would help to get a clearer understanding of its role in the management of PPHN, particularly for use in resource-limited settings that lack iNO.Clinical trial registration:https://ctri.nic.in/Clinicaltrials/rmaindet.php? trialid=63997&EncHid=39716.16132&modid=1&compid=19[CTRI/2022/06/043328].

Plasmapheresis for extracorporeal membrane oxygenation (ECMO)-induced hemolysis in infants

Background: Intravascular hemolysis is a known complication of extracorporeal membrane oxygenation (ECMO). Characterized by elevated plasma-free hemoglobin (PFH), intravascular hemolysis is associated with cytotoxic effects leading to renal replacement therapy (RRT), longer ECMO runs and mortality. Therapeutic plasma exchange (TPE) in tandem with ECMO was described as a therapy for various pathologic conditions, but there are no ELSO guidelines for the treatment of ECMO-induced hemolysis. We describe the use of TPE in the management of severe ECMO-induced hemolysis. Methods: Two term neonates receiving veno-arterial (VA) ECMO developed severe PFH, with peak values over 500 mg/dL. TPE was performed in tandem with the ECMO circuit. Packed red cells were used to prime the TPE circuit, and citrate anticoagulation was added to establish the interface, which could not be achieved with existing heparin in the ECMO circuit. Therapy was completed with saline solution as a decoy for citrate, to avoid hypocalcemia and intracranial bleeding. Plasma volume was replaced by fresh frozen plasma (FFP). Results: In one patient PFH fell to 120 mg/dL, but rebounded to close to 500 mg/dL, only to stabilize between 210 and 300 mg/dL after the second TPE. He was liberated from ECMO, but could not survive a respiratory decompensation. The other patient’s PFH improved to 360 mg/dL after one TPE and continued to decline to 120 mg/dL over the ensuing days. Despite that improvement, care was withdrawn. Conclusion: TPE is effective in decreasing the burden of PFH, is well tolerated in tandem with ECMO, and a database of infants with ECMO-induced hemolysis needs to be created to assess the current practice, and establish clinical guidelines for its most appropriate therapy.

Effects of Limosilactobacillus reuteri DSM 17938 in neonates exposed to antibiotics: a randomised controlled trial.

Perinatal antibiotic exposure potentially leads to gut microbiota dysbiosis, which is associated with functional gastrointestinal disorders (FGIDs). We aimed to investigate the effects of Limosilactobacillus reuteri DSM 17938 supplementation on the development of FGIDs, crying and sleep duration, and the gut microbial composition in infants exposed to antibiotics during the neonatal period. In this randomised, double-blind, placebo-controlled study, we included 89 term neonates treated with antibiotics. Neonates received the study product for six weeks. FGIDs, assessed by the Infant Gastrointestinal Symptom Questionnaire, crying and sleep duration were assessed at four and eight weeks, and six months after enrolment. Faecal samples were collected six weeks and twelve months after enrolment. The gut microbial community composition was analysed using 16S amplicon sequencing and qPCR. The proportion of infants with FGIDs was greater in the control group, although the difference between the groups was significant only six months after enrolment. At all time points, the probiotic group presented a longer sleep duration and shorter crying time than the control group, but the difference was not statistically significant. Probiotic consumption had no significant effect on the gut microbiota composition except for increased L. reuteri DSM 17938 abundance in the probiotic group at six weeks after enrolment. At specific time points after supplementation with L. reuteri DSM 17938, a reduction in the prevalence of FGIDs was observed in the probiotic group. However, no observable effect on the gut microbiota was detected during the intervention. We believe that probiotic supplementation in neonates during and after antibiotic treatment to minimise the negative effects of antibiotics on gut function during this vulnerable period of human development warrants further investigation. The trial is registered at ClinicalTrials.gov (NCT02865564).

Effect of aluminum foil reflector on serum bilirubin and duration of phototherapy among term neonates undergoing phototherapy for hyperbilirubinemia: A randomized controlled trial

Background: Jaundice is a common clinical issue especially in the first week of life and one of the leading causes for readmission to the hospital. This study aimed to assess the effect of aluminium foil reflector on serum bilirubin level ,duration of phototherapy and duration of hospital stay. Methods: A randomized controlled trial was carried among 50 term neonatesin neonatal intensive care unit(NICU) .Term neonates were randomly assigned in to experimental and control group by block randomization. Consecutive sampling technique was used to enroll the neonates who met the inclusion criteria. During photo therapy neonates in the control group received standard careand the neonatesin the experimental group received standard care along with aluminium foil reflector around all the four sides of neonatal cot. Data were analysed using chi square test, fisher exact test and independentt-test. Results: After the intervention the serum bilirubin levels in the experimental and control groupswere13.20±3.35 and 14.07±3.12 respectively (P = 0.348),total duration of phototherapy in hours in experimental group and control groupswere 35.76±17.20 and 38.08±16.36 respectively(P = 0.627) and duration of hospital stay in days in experimental group and control group were 2.6±0.91 and 2.92±1.22 respectively (P = 0.299). Conclusion: Aluminium foil reflector aids in decreasing bilirubin level, reduced the duration of phototherapy and duration of hospital stay among term neonates.

The safety of pathogen-reduced platelet transfusions in critically ill term and preterm neonates.

Platelet transfusions carry an important risk of infection transmission. The Mirasol Pathogen Reduction Technology system for platelets uses riboflavin and UV light to introduce irreparable lesions into nucleic acids, thereby inhibiting pathogen replication and inactivating white blood cells. The objective of this study is to evaluate the safety of pathogen-reduced platelet transfusions (PRPTs) in critically ill infants in a neonatal intensive care unit (NICU) in the Caribbean. We conducted a descriptive retrospective study of the use of Mirasol PRPTs in patients admitted to the NICU of the general hospital in Curaçao from February 2016 to April 2023. A total of 208 PRPTs were administered to 46 patients (median [range] transfusions per patient: 3 [1-24]). Three patients were born term, and 43 were born preterm (median [range] gestational age: 27 4/7 weeks [24 6/7-36 6/7]). PRPTs were well-tolerated and no complications occurred, especially no signs of haemolysis nor any signs of new infection within 24 h after transfusion. Twenty-one of 46 patients (46%) died during their admittance. None of the deaths were deemed related to PRPT. Mirasol PRPT appears to be safe for use in critically ill neonates, including extremely preterm neonates.

Regional Differences in Lung Ventilation During the Early Transition Period in Late Preterm and Term Neonates Assessed by Electrical Impedance Tomography

Background: Changes in lung ventilation are well documented in term neonates while in late preterm neonates these patterns are poorly understood despite their increased risk of respiratory morbidity. Objectives: The study aimed to compare and clarify the differences in regional lung ventilation of late preterm and term neonates during the early adaptation period using electrical impedance tomography (EIT). Material and methods: The case-control study was conducted in the years 2020–2022. It included 51 late preterm neonates (LPN, Study group) and 45 term neonates (TN, Control) born by normal vaginal delivery (NVD). EIT examinations were performed with a Swisstom BB2 (Switzerland) equipment. The data recordings were performed no later than 30 (I Record), 60 (II), and 90 (III) minutes after the birth. Results: Statistically significant differences between LPN and TN were observed in the non-dependent lung areas at I record, with more silent spaces observed in the LPN (p &lt; 0.001). Differences in the dependent lung regions were observed across all recordings, with LPN demonstrating more silent spaces (p &lt; 0.001). LPN demonstrated greater stretch-related changes in the 10% and 20% stretch categories across all recordings, while TN showed greater changes in the 50%, 70%, and 90% categories. Tidal volumes in the right lung of TN are distributed more towards the ventral and central ventral regions. In contrast, tidal volumes of LPN are distributed to the central dorsal and dorsal regions of the right lung. Conclusions: LPN during the first 90 min after the birth show reduced lung ventilation assessed by EIT, suggesting a possible impairment of early postnatal adaptation.

Functional echocardiography for management of shock in neonates - study protocol for a randomized controlled trial

Background: Shock is common in sick neonates and is associated with a high mortality. Detection and management of shock by monitoring clinical parameters may be inadequate due to inconsistent association with tissue perfusion. We hypothesize that objective assessments of cardiac functions may help to match the pathophysiology of shock with the pharmacological action of a vasoactive drug. This may lead to earlier resolution of shock and reduced incidence of mortality or brain injury. To test this hypothesis, this study aims to evaluate the efficacy of adding functional echocardiography to standard clinical assessment in improving short-term outcome of neonates with clinical features of shock. Methods: This study will be an open-labeled randomized controlled trial, conducted in all inborn neonates born at &gt;27 weeks of gestation who develop clinical signs of shock. Enrolled neonates will be randomized into two groups: the echo group and the control group. Neonates in the echo group will be assessed for management of shock by both standard clinical evaluation and functional echocardiography. Neonates in the control group will be assessed for the management of shock by standard clinical evaluation. Primary outcome will be survival without requirement of inotropic support at 72 hours of randomization. Secondary outcomes include time to hemodynamic stability, duration of inotropic support and incidence of abnormal cranial ultrasound. Results: Among the 154 patients in the Clinical Trial Group, 70/154 (45%) continued to have proteinuria, while 84/154 (55%) had no proteinuria (remission) compared to 41 (28%) in remission and 104 (72%) with continued proteinuria in the Usual Care group (p&lt;0.001). Conclusions: The trial intends to deduce the advantages, if any, of addition of functional echocardiography to standard clinical assessment to guide management of shock among preterm and term neonates. Trial registration: CTRI number: CTRI/2023/08/056672.

Illicit Fentanyl in the Prenatal Period: A Significant Emerging Risk for Neonatal Opioid Withdrawal Syndrome

Objective This study aimed to evaluate the impact of in-utero illicit fentanyl exposure on neonatal outcomes, including neonatal opioid withdrawal syndrome (NOWS), length of stay (LOS), and treatment requirements. Study Design This study was conducted from March 2020 to December 2022, and focused on neonates born to mothers with opioid use or opioid use disorder (OUD). Maternal opioid use was identified through self-report or umbilical cord tissue (UCT) testing. Severe NOWS was defined as cases requiring pharmacological treatment. Statistical analyses included univariate comparisons, logistic regression, and generalized linear models to assess the associations between fentanyl exposure and neonatal outcomes. Results Forty-seven percent (75/159) of infants had in-utero fentanyl exposure. Fentanyl-positive mothers were older, 31 ± 5 years, compared to non-fentanyl mothers, 29 ± 5, p = 0.01. They were also less likely to receive prenatal care (p &lt; 0.01) and had a higher number of polysubstance used, 5 ± 1 compared to non-fentanyl mothers, 3 ± 1, p &lt; 0.01. Overall, infants exposed to fentanyl had a higher incidence of severe NOWS (odds ratio = 5.8, 95% confidence interval [CI]: 2.49–12.95, p &lt; 0.01) and required earlier NOWS treatment initiation, 1 ± 1 day compared to non-exposed infants 3 ± 2 days, p &lt; 0.01. In adjusted analysis, fentanyl exposure was associated with a nearly three-fold increased risk of NOWS (Mantel–Haenszel combined relative risk = 2.98, 95% CI: 1.94–4.57). Furthermore, fentanyl exposure led to longer LOS, with a 40% increase for preterm neonates (p &lt; 0.01) and a 63% increase for full-term neonates (p &lt; 0.01). Additionally, there was a significant correlation between log fentanyl concentration in umbilical cord tissue and cumulative morphine dose required for NOWS treatment, p = 0.001. Conclusion Prenatal illicit fentanyl exposure is an independent and strong risk factor for severe NOWS presentation in newborns requiring extended hospital stays. Key Points

Atypical neonatal cutaneous myiasis: A diagnostic challenge mimicking pustular rash in a resource-limited setting.

Neonatal cutaneous myiasis is a rare disease in newborns. Although it is unlikely, the level of suspicion for this condition should be high, especially in tropical regions. Treatment may deviate from the standard approach when necessary, and chemical debridement can be considered, particularly for smaller lesions. Ultimately, clinical judgment plays a key role in decision-making. Myiasis is the infestation of the skin of a mammal by larvae or maggots. The skin is the most affected organ. However, it can also affect other organs of the body. Gasterophilus and Hypoderma are two flies that produce creeping myiasis, a type of cutaneous myiasis our patient had. The infestation is common in Sub-Saharan Africa and most especially among rural dwellers. We report on a case of a 7-day-old term neonate who reported to St. Mary's Hospital Lacor, a Private-not-for-Profit hospital situated in the Northern region of Uganda, who was admitted as a case of neonatal sepsis with a focus on the skin initially, however, while on the ward was eventually diagnosed with Cutaneous Myiasis. The management plan included chemical debridement with Hydrogen peroxide, IV antibiotics, and other supportive therapies, and the neonate was ultimately discharged home after 9 days in the NICU. This case report aims to inform healthcare workers of the importance of heightening the index of suspicion of myiasis for neonates who present with sudden-onset rash that can resemble pustules and be mistaken for a pustular rash. Additionally, chemical debridement, in this case, underscores the importance of an innovative approach to managing cutaneous myiasis in resource-limited settings. Mass education and awareness programs focusing on proper hygiene practices, safe handling of newborns, and early recognition of symptoms can help mitigate the risk of myiasis.

Predictive Value of Cord Blood Bilirubin for Hyperbilirubinemia in Term Neonates with ABO Incompatibility

Introduction: Jaundice affects 60% of full-term and 80% of preterm neonates. Feto-maternal ABO incompatibilities occur in 20-25% of pregnancies, but severe haemolytic disease develops in only 10%. ABO-incompatible babies have doubled the risk of jaundice requiring treatment and a 5-10 times increased risk of exchange transfusions. Objective: Aim of this study was to determine if cord blood bilirubin (CBB) can predict hyperbilirubinemia in term babies with ABO setup prior to discharge that would help to decrease readmission and subsequently complications due to jaundice. Methods: A hospital-based prospective observational study was conducted at Patan Hospital. Cord blood group and bilirubin levels were collected from newborns of O positive mothers. Babies with A positive and B positive blood groups had their CBB levels measured and were followed daily for 72 hours. Serum bilirubin was tested based on clinical judgment to detect hyperbilirubinemia and treated per NICE guidelines. Data were analysed using SPSS v21.0, Mann-Whitney test, ANOVA, and ROC analysis. Results: Among 66 cases, significant hyperbilirubinemia was seen in 7 neonates (10.6%). It was more common in B positive babies (12.2%) compared to A positive (8%). Mean CBB was 3.45 ± 0.57 in those developing significant hyperbilirubinemia. A CBB of 2.95 mg/dL had the highest sensitivity (86%), specificity (94%), and negative predictive value (98%) for predicting hyperbilirubinemia in ABO setup babies. Conclusion: Term babies with ABO incompatibility and CBB&lt;2.95 mg /dL are unlikely to need further evaluation, while those with cord bilirubin level ≥2.95 mg/dL should have frequent early follow-ups.

White matter functional networks in the developing brain

BackgroundFunctional magnetic resonance imaging (fMRI) is widely used to depict neural activity and understand human brain function. Studies show that functional networks in gray matter undergo complex transformations from neonatal age to childhood, supporting rapid cognitive development. However, white matter functional networks, given the much weaker fMRI signal, have not been characterized until recently, and changes in white matter functional networks in the developing brain remain unclear.PurposeAims to examine and compare white matter functional networks in neonates and 8-year-old children.MethodsWe acquired resting-state fMRI data on 69 full-term healthy neonates and 38 healthy 8-year-old children using a same imaging protocol and studied their brain white matter functional networks using a similar pipeline. First, we utilized the ICA method to extract white matter functional networks. Next, we analyzed the characteristics of the white matter functional networks from both time-domain and frequency-domain perspectives, specifically, intra-network functional connectivity (intra-network FC), inter-network functional connectivity (inter-network FC), and fractional amplitude of low-frequency fluctuation (fALFF). Finally, the differences in the above functional networks’ characteristics between the two groups were evaluated. As a supplemental measure and to confirm with literature findings on gray matter functional network changes in the developing brain, we also studied and reported functional networks in gray matter.ResultsWhite matter functional networks in the developing brain can be depicted for both the neonates and the 8-year-old children. White matter intra-network FC within the optic radiations, corticospinal tract, and anterior corona radiata was lower in 8-year-old children compared to neonates (p &amp;lt; 0.05). Inter-network FC between cerebral peduncle (CP) and anterior corona radiation (ACR) was higher in 8-year-olds (p &amp;lt; 0.05). Additionally, 8-year-olds showed a greater distribution of brain activity energy in the high-frequency range of 0.01–0.15 Hz. Significant developmental differences in brain white matter functional networks exist between the two group, characterized by increased inter-network FC, decreased intra-network FC, and higher high-frequency energy distribution. Similar findings were also observed in gray matter functional networks.ConclusionWhite matter functional networks can be reliably measured in the developing brain, and the differences in these networks reflect functional differentiation and integration in brain development.

Neurodevelopmental outcome in children between one and five years after persistent pulmonary hypertension of term and near-term newborns

BackgroundPersistent pulmonary hypertension of the newborn (PPHN) is a serious condition that affects 1–2 per 1,000 newborns. Scientific data report the existence of neurological developmental abnormalities between 10 and 30%, but the description of these disorders linked with this situation of cerebral hypoxia and haemodynamic failure remains poorly documented.ObjectiveThe main goal of this study was to describe the prevalence of neuro-psychomotor developmental disorders in children aged between one and five years old who have been hospitalised at birth in a neonatal intensive care unit for the management of PPHN.MethodsAll of the newborns ≥34 weeks of gestational age (WGA) with PPHN, treated with inhaled nitric oxide in our neonatal intensive care unit between January 2015 and December 2019 were retrospectively enrolled. An ASQ-3 standardised questionnaire, adapted to the appropriate age (12, 24, 36, 48 and 60 months) was performed by the parents.ResultsFifty-five children (81% of answers) with a median age of 36 months (11–68), whose real age was close to the one of the questionnaire (12, 24, 36, 48 and 60 months), have been included in this study. There was 47% of pathological score [borderline: less than 1 standard deviation (SD) or suspect: less than 2SD] in at least one of the five studied domains, mainly in communication (25%) and individual and social skills (22%), despite a high overall score of 250 [220; 285] out of 300 that improved with age.ConclusionThis study showed a significant prevalence of neuro-psychomotor developmental disorders which justifies making more accessible a prolonged and adapted follow-up for early and multidisciplinary screening and management of these children with PPHN history. Larger cohorts are needed to better explore long term outcome of these vulnerable term neonates.

Neonatal reference intervals for serum steroid hormone concentrations measured by LC-MS/MS.

Congenital adrenal hyperplasia (CAH) is a rare, inherited disorder of adrenal steroid synthesis. In many countries it is part of the neonatal screening program enabling early diagnosis and treatment. In case of an abnormal neonatal screening result or when other differences of sexual development (DSD) are suspected, measurement of serum steroid hormones using liquid chromatography coupled to mass spectrometry (LC-MS/MS) is needed for further diagnosis. However, reliable age- and sex-specific reference intervals (RIs) for serum steroid hormones during the neonatal period are missing. We therefore aimed to establish LC-MS/MS based RIs for serum steroid hormones in neonates. Serum was obtained from healthy term neonates at two time points: 130 samples at day 3-8 (T1, time of the neonatal screening) and 126 samples at day 13-15 (T2,two weeks old). Concentrations of cortisol, cortisone, corticosterone, 11-deoxycortisol, 21-deoxycortisol, 11-deoxycorticosterone, testosterone, androstenedione, and 17-hydroxyprogesterone (17-OHP) were measured using LC-MS/MS. RIs (in nmol/L) were established for T1 and T2: cortisone (19.3-215;18.0-212), cortisol (10.0-407;8.4-446), corticosterone (<31;<50), 11-deoxycortisol (0.73-4.6;0.70-3.6), 17-OHP (<4.9;<5.1), androstenedione (0.3-1.8;0.3-2.7), 11-deoxycorticosterone (<0.2;<0.2), and 21-deoxycortisol (<1;<1), respectively. Testosterone differed between boys and girls: RIs at T1 and T2 for boys were 0.27-4.3 and 0.63-13.9, and for girls<0.30 and <0.47, respectively. We established LC-MS/MS based RIs for cortisol, cortisone, corticosterone, 11-deoxycortisol, 21-deoxycortisol, 11-deoxycorticosterone, testosterone, androstenedione, and 17-OHP in neonates in the first and second week of life.

Common Causes of Neonatal Seizure among Neonates Admitted to Neonatal Care Unit at Al Ramadi Teaching Hospital for Maternity and Children

Neonatal seizures are the transient occurrence of signs and symptoms due to an abnormal excessive or synchronous neuronal activity in the neural cells causing paroxysmal electro clinical changes. Neonates are at high risk for seizures as compared to other age groups. The aim of this study was to identify the common causes that lead to neonatal seizure during the period from first of October 2020 to the end of July 2021using history, physical examination, and investigations in Al Ramadi teaching hospital for maternity and children. The total number of neonates diagnosed as neonatal seizure during the period of study in Al Ramadi teaching hospital for maternity and childhood was 64 cases. Total number of admissions to neonatal care unit was 4102 so the prevalence in neonatal care unit was 15.6 per 1000 live births. 30 (47.1 %) cases were diagnosed as perinatal asphyxia, 18 (28 %) cases were diagnosed as metabolic, 6 (9.4 %) cases were diagnosed as infections, seizures, 4 (6.3%) cases were diagnosed as intracranial hemorrhage, 3(4.6%) cases were diagnosed as CNS malformation, while 3 cases (4.6 %) were Unknown etiology. 38 (59.3%) of studied neonatal seizures were male, while 26 (40.7%) were female. Male to female ratio was (1.4:1). 37 (57.8%) were term babies (≥37 gestational age), while 27 (42.2%) were preterm babies (&lt;37 gestational age). 41 (64%) of studied neonatal seizure cases were born by normal vaginal delivery, while 23 (36%) of cases were born by caesarian section delivery. The most common cause of neonatal seizure was perinatal asphyxia followed by metabolic causes then infection, intracranial hemorrhage, CNS malformations and unknown causes. Male are more common than female. In term neonates more common than preterm and in normal vaginal delivery more than cesarean section.

EFFECTIVENESS OF MAGNESIUM SULFATE IN TERM NEONATES HAVING PERINATAL ASPHYXIA

In Pakistan, neonatal mortality and morbidity are remarkably high. Birth asphyxia (perinatal asphyxia) is one of the main contributors to this, apart from prematurity, sepsis and other causes. Objective: To assess the effectiveness of magnesium sulfate in term neonates having perinatal asphyxia Methods: This Randomized Controlled Trial was carried out at the Department of Pediatrics, Sheikh Zayed Hospital Rahim Yar Khan from July 2023 to December 2023. The overall sample size was 130 patients (65 patients in each group). Neonates in group A received MgSO through I/V, 3 doses 250mg/kg/dose, 24 hours apart along with standard treatment. Group B was a control group that received 20 ml of normal saline infusion at the same interval with similar supportive and symptomatic treatment with regular monitoring. The outcome in terms of mortality, seizure, early initiation of feed, time to the establishment of full oral feeding, duration of seizures and duration of hospital stay were assessed. All the data was analyzed by using SPSS version 25.Results: In the current study, a total of 130 neonates were enrolled. Among them, moderate asphyxia was observed in 90 (69.23%) patients whereas severe perinatal asphyxia was observed in 40(30.77%) patients. In group A, the mean level of serum magnesium in neonates with moderate asphyxia was 2.81 (±0.20) mEq/L while in neonates with severe asphyxia, it was 2.89 (±0.61) mEq/L. The moderate asphyxia patients in group-A showed significant statistical improvement in terms of seizure control (hours) (14.11±1.22 vs 18.11±1.56; P=0.01), normal cry appearance (Days) (11.1±0.12 vs 13.11±1.29; p=0.03), normal activity appearance (Days) (11.9±0.02 vs12.00±1.51; p=0.01), full oral feed acceptance by sucking (Days) (13.31±0.99 vs 14.61±1.51; p=0.01) and mean hospital stay duration (Days) (14.99±1.66 vs 16.21±1.11; p 0.02). Conclusion: Our study concludes that in asphyxiated newborns, postnatal magnesium sulphate infusion is safe and likely to enhance the short-term neurological prognosis in cases with moderate-grade encephalopathy.

Exploring the Impact of Developmental Clearance Saturation on Propylene Glycol Exposure in Adults and Term Neonates Using Physiologically Based Pharmacokinetic Modeling.

Propylene glycol (PG) is a pharmaceutical excipient which is generally regarded as safe (GRAS), though clinical toxicity has been reported. PG toxicity has been attributed to accumulation due to saturation of the alcohol dehydrogenase (ADH)-mediated clearance pathway. This study aims to explore the impact of the saturation of ADH-mediated PG metabolism on its developmental clearance in adults and neonates and assess the impact of a range of doses on PG clearance saturation and toxicity. Physiologically based pharmacokinetic (PBPK) models for PG in adults and term neonates were developed using maximum velocity (Vmax) and Michaelis-Menten's constant (Km) of ADH-mediated metabolism determined in vitro in human liver cytosol, published physicochemical, drug-related and ADH ontogeny parameters. The models were validated and used to determine the impact of dosing regimen on PG clearance saturation and toxicity in adults and neonates. The Vmax and Km of PG in human liver cytosol were 1.57 nmol/min/mg protein and 25.1 mM, respectively. The PG PBPK model adequately described PG PK profiles in adults and neonates. The PG dosing regimens associated with saturation and toxicity were dependent on both dose amount and cumulative in standard dosing frequencies. Doses resulting in saturation were higher than those associated with clinically observed toxicity. In individuals without impaired clearance or when PG exposure is through formulations that contain excipients with possible interaction with PG, a total daily dose of 100-200 mg/kg/day in adults and 25-50 mg/kg/day in neonates is unlikely to result in toxic PG levels or PG clearance saturation.

Estimation of Gestational Age-Specific Reference Intervals for Coagulation Assays in a Neonatal Intensive Care Unit Using Real-World Clinical Data

Abstract Interpretation of coagulation testing in neonates currently relies on reference intervals defined from adult cohorts. These likely do not reflect the normative values for neonates, in whom immature synthesis of vitamin K-dependent factors may contribute to this divergence. Direct reference interval estimation studies are difficult, particularly in neonatal populations; however, advances in indirect estimation may allow us to infer normative distributions from routinely collected clinical data. To accomplish this, initial coagulation testing results from all patients admitted to a level IV neonatal intensive care unit between 1/1/2018 - 1/1/2023 were extracted from the electronic health record and analyzed. Results prior to June 2021 were performed on the viscosity-based STA Compact Max (Diagnostica Stago. Parsippany, NJ, USA). Afterward, results were performed on a nephelometry-based ACL Top (Instrumentation Laboratory. Bedford, MA, USA). Specimens collected after transfusion of blood products were excluded. Prothrombin times (PT) and international normalized ratios (INR) were available for 1,117 neonates, while activated partial thromboplastin times (aPTT) were available for 790 neonates. The 95% confidence intervals (CI) of the median PT for extremely preterm, very preterm, preterm and term neonates were [19 - 21s], [18 - 22s], [17 - 19s] and [17 - 18s]. For INR, the CI were [1.6 - 1.8], [1.5 - 1.8], [1.4 - 1.6], and [1.4 - 1.5]. For aPTT, the CI were [51 - 61s], [47 - 58s], [45 - 50s], and [42 - 46s]. Indirect reference intervals (IRIs) were then estimated across gestational age groups (binning all patients delivered at less than 37 weeks into one preterm category) using refineR. The IRI for PT was 10 - 24s for preterm,10 - 22s for term, and 10 - 24s for all neonates. The IRI for INR was 0.7 - 2.1 for preterm, 0.8 - 1.8 for term, and 0.8 - 1.9 for all neonates. The IRI for aPTT was 24.5 - 68.4s for preterm, 24.7 - 58.2s for term, and 25 - 62.3s for all neonates. When compared to currently reported reference intervals, the lower limits of the IRI were similar to currently reported reference intervals; however, the upper limits of the IRIs were 1.3 - 1.8 times higher than current reference intervals. Theoretically, implementation of these IRIs would lead to a 3-fold decrease in the number of results flagged as abnormal. In conclusion, IRIs for coagulation assays estimated from neonates using routine clinical data show substantial divergence from current reference intervals in their upper limits, possibly due to the decreased factor concentrations seen prior to liver maturation. If implemented, these IRIs would substantially reduce the proportion of abnormal results. Future work will explore whether switching to these reference intervals could lead to a reduction in unnecessary transfusions or improved clinical outcomes.