OBJECTIVE: The aim of this proof-of-concept study was to evaluate whether combining population pharmacokinetic and machine learning approaches could provide a more accurate prediction of the clearance of renally eliminated drugs in individual neonates.
METHODS: Six drugs that are primarily eliminated by the kidneys were selected (vancomycin, latamoxef, cefepime, azlocillin, ceftazidime, and amoxicillin) as 'proof of concept' compounds. Individual estimates of clearance obtained from population pharmacokinetic models were used as reference clearances, and diverse machine learning methods and nested cross-validation were adopted and evaluated against these reference clearances. The predictive performance of these combined methods was compared with the performance of two other predictive methods: a covariate-based maturation model and a postmenstrual age and body weight scaling model. Relative error was used to evaluate the different methods.
RESULTS: The extra tree regressor was selected as the best-fit machine learning method. Using the combined method, more than 95% of predictions for all six drugs had a relative error of < 50% and the mean relative error was reduced by an average of 44.3% and 71.3% compared with the other two predictive methods.
CONCLUSION: A combined population pharmacokinetic and machine learning approach provided improved predictions of individual clearances of renally cleared drugs in neonates. For a new patient treated in clinical practice, individual clearance can be predicted a priori using our model code combined with demographic data.
METHODS: Computational Fluid Dynamics (CFD) approach is used to simulate the airflow in a neonate, an infant and an adult in sedentary breathing conditions. The healthy CT scans are segmented using MIMICS 21.0 (Materialise, Ann arbor, MI). The patient-specific 3D airway models are analyzed for low Reynolds number flow using ANSYS FLUENT 2020 R2. The applicability of the Grid Convergence Index (GCI) for polyhedral mesh adopted in this work is also verified.
RESULTS: This study shows that the inferior meatus of neonates accounted for only 15% of the total airflow. This was in contrast to the infants and adults who experienced 49 and 31% of airflow at the inferior meatus region. Superior meatus experienced 25% of total flow which is more than normal for the neonate. The highest velocity of 1.8, 2.6 and 3.7 m/s was observed at the nasal valve region for neonates, infants and adults, respectively. The anterior portion of the nasal cavity experienced maximum wall shear stress with average values of 0.48, 0.25 and 0.58 Pa for the neonates, infants and adults.
CONCLUSIONS: The neonates have an underdeveloped nasal cavity which significantly affects their airway distribution. The absence of inferior meatus in the neonates has limited the flow through the inferior regions and resulted in uneven flow distribution.
MATERIAL AND METHODS: This was a double-blind, placebocontrolled trial conducted among women planned for emergent caesarean delivery for suspected foetal compromise where 100 were randomised to receive subcutaneous terbutaline or placebo. The primary outcomes were the neonatal acid-base status, while the 5- minute Apgar score, admission to the intensive care unit and the maternal outcomes were recorded as secondary outcomes.
RESULTS: Data from a total of 96 women were analysed and showed a lower incidence of neonatal acidemia (4.4% vs 10.4%) and fewer neonates born with umbilical artery pH of less than 7.20 (12.5% vs 27.1%) and 7.10 (4.2% vs 6.2%) after terbutaline injection. However, the difference in the incidence of neonatal acidaemia, mean cord pH and base excess, Apgar score or admission to the intensive care unit did not differ significantly. No difference was seen in the maternal mean arterial pressure, estimated blood loss or haematocrit after the surgery between the study groups. The only significant maternal effect was tachycardia which was more common after terbutaline injection (54.2% vs 25.0 %, p=0.003).
CONCLUSION: The study shows that acute tocolysis with subcutaneous terbutaline prior to caesarean delivery has the potential to improve the neonatal outcome in suspected intrauterine foetal compromise and should be further investigated.
MATERIALS AND METHODS: The U5M surveillance data from 2015 to 2017 was retrieved for Malaysian cases of stillbirths and neonatal deaths with multiple pregnancies as exclusion. Stillbirth and neonatal death cases were analysed descriptively for socio-demographic and clinical characteristics. Logistic regressions were performed to identify the associated factors.
RESULTS: There were 15,444 cases selected for analysis, of which 55% of stillbirths and 45% of neonatal deaths. There were 21% of preventable deaths (U5M) and the major contributing causes of preventable stillbirths and neonatal deaths were classified as perinatal death (82.5%), infectious and parasitic diseases (4.1%) and congenital malformations (3.5%). The birth weight (aOR 6.03, 95% CI: 4.14-8.79), hypertensive mother (aOR 1.88, 95% CI: 1.66-2.12) and instrumental delivery (aOR 1.64, 95% CI: 1.16-2.31) were significantly associated with preventable stillbirths and neonatal deaths. Higher household income (>RM3000 per month) was noted as a protective factor (aOR 0.79, 95% CI:0.69,0.89). Mothers with ethnicities other thanBumiputera, single mothers and housewives were identified as the group of mothers with higher odds of poor perinatal services. Among the 3242 cases of preventable stillbirths and neonatal deaths with a complete documented level of adequacy and quality of healthcare, the most frequently identified factors were due to insufficient antenatal care (ANC) (20.4%), non-compliance with medical advice (12.3%) and unsuitable place of delivery (8.6%).
CONCLUSION: Increasing trend of preventable stillbirths and neonatal deaths was noted over 3 years (2015-2017), and one-fifth was related to insufficient ANC service-related factors. Remedial measures in improving the quality of ANC services with an emphasis on the targeted high-risk maternal socio-demographic group (other Bumiputera, older antenatal mothers, nonmarried, poor family income neglected family) and enhancing ANC competency skills among the healthcare provider through adequate training are required to decrease preventable stillbirths and neonatal deaths in Malaysia.
OBJECTIVE: This study aimed to compare Foley balloon catheter placement for 6 vs 12 hours in induction of labor after 1 previous cesarean delivery.
STUDY DESIGN: A randomized controlled trial was conducted in a university hospital in Malaysia from January 2022 to February 2023. Eligible women with 1 previous cesarean delivery admitted for induction of labor were enrolled. Participants were randomized after balloon catheter insertion for 6 or 12 hours of passive ripening before balloon deflation and removal to check cervical status for amniotomy. The primary outcome was the induction of labor to delivery interval. The secondary outcomes were largely derived from the core outcome set for trials on induction of labor (Core Outcomes in Women's and Newborn Health [CROWN]). The Student t test, Mann-Whitney U test, chi-square test, and Fisher exact test were used as appropriate for the data.
RESULTS: Overall, 126 women were randomized, 63 to each intervention. The mean induction of labor to delivery intervals were 23.0 (standard deviation, ±8.9) in the 6-hour arm and 26.6 (standard deviation, ±7.1) in the 12-hour arm (mean difference, -3.5 hours; 95% confidence interval, -6.4 to -0.7; P=.02). The median induction of labor (Foley balloon catheter insertion) to Foley balloon catheter removal intervals were 6.0 hours (interquartile range, 6.0-6.3) in the 6-hour arm and 12.0 hours (interquartile range, 12.0-12.5) in the 12-hour arm (P
CASE PRESENTATION: Herein, we report a case of very severe hypertriglyceridemia 32 mmol/L (2834 mg/dL) detected incidentally at three months old in an otherwise well boy born late preterm with intrauterine growth restriction, when he presented with lipaemic plasma. He was later diagnosed with CLS. No pathogenic mutations were found for hypertriglyceridemia, and no secondary causes could explain his very severe hypertriglyceridemia.
CONCLUSIONS: The very severe hypertriglyceridemia in this case may appear to be a serious presentation of an unrecognised clinical feature of CLS, further expanding its phenotype.
METHODS: Published population pharmacokinetic models and the Australasian Neonatal Medicines Formulary were used to simulate antimicrobial concentration-time profiles in a virtual neonate population. Laboratory quality assurance data were used to quantify analytical variation in antimicrobial measurement methods used in clinical practice. Guideline-informed dosing recommendations based on drug concentrations were applied to compare the impact of analytical variation and nonanalytical factors on antimicrobial dosing.
RESULTS: Analytical variation caused differences in subsequent guideline-informed dosing recommendations in 9.3-12.1% (amikacin), 16.2-19.0% (tobramycin), 12.2-45.8% (gentamicin), and 9.6-19.5% (vancomycin) of neonates. For vancomycin, inaccuracies in drug administration time (45.6%), use of non-trough concentrations (44.7%), within-subject biological variation (38.2%), and dosing errors (27.5%) were predicted to result in more dosing discrepancies than analytical variation (12.5%). Using current analytical performance specifications, tolerated dosing discrepancies would be up to 14.8% (aminoglycosides) and 23.7% (vancomycin).
CONCLUSIONS: Although analytical variation can influence neonatal antimicrobial dosing recommendations, nonanalytical factors are more influential. These result in substantial variation in subsequent dosing of antimicrobials, risking inadvertent under- or overexposure. Harmonization of measurement methods and improved patient management systems may reduce the impact of analytical and nonanalytical factors on neonatal antimicrobial dosing.
METHODOLOGY: This was a retrospective cohort study that included 170 newborns admitted to the Neonatal Intensive Care Unit (NICU) of Hospital Universiti Sains Malaysia (HUSM) with a history of maternal hyperthyroidism from January 2013 until December 2018. We analyzed their baseline demographic and clinical characteristics, maternal thyroid status and antibody levels. Finally, we analyzed newborn thyroid function and thyroid antibodies.
RESULTS: The proportion of neonates born to mothers with maternal hyperthyroidism was 0.8% (170 of 20,198 neonates within the study period). Seven (4.1%) developed overt hyperthyroidism, while four (2.4%) had thyroid storm. The median time for thyroid function test normalization was 30 days (95% CI: 27.1 to 32.8). The median time for TFT normalization was longer among neonates of mothers with positive thyroid antibodies [46.6 days (95% CI, 20.6 to 39.4)] and of mothers who received anti-thyroid treatment [31.7 days (95% CI, 23.5 to 39.9)].
CONCLUSION: Neonates born to mothers with hyperthyroidism is uncommon. These babies were observed to have a longer time for normalization of thyroid function tests if their mothers had thyroid antibodies or received anti-thyroid treatment.