The Pharmacokinetics of Caffeine in Preterm Newborns: No Influence of Doxapram but Important Maturation with Age

Background: Apnea of prematurity can persist despite caffeine therapy in preterm infants. Doxapram may additionally support breathing. Although multiple small studies have reported the efficacy of doxapram, the structural co-treatment with caffeine impedes to ascribe the efficacy to doxapram itself or to a pharmacokinetic (PK) interaction where doxapram increases the exposure to caffeine. We examined whether there is a PK drug-drug interaction between doxapram and caffeine by developing a PK model for caffeine including infants with and without doxapram treatment. Methods: In preterm neonates receiving caffeine, we determined caffeine plasma concentrations before, during, and directly after doxapram co-treatment and used these to develop a population PK model in NONMEM 7.3. Patient characteristics and concomitant doxapram administration were tested as covariates. Results: 166 plasma samples were collected from 39 preterm neonates receiving caffeine (median gestational age 25.6 [range 24.0–28.0] weeks) of which 65 samples were taken during co-treatment with doxapram (39%, from 32/39 infants). Clearance of caffeine was 9.99 mL/h for a typical preterm neonate with a birth weight of 0.8 kg and 23 days postnatal age and increased with birth weight and postnatal age, resulting in a 4-fold increase in clearance during the first month of life. No PK interaction between caffeine and doxapram was identified. Discussion: Caffeine clearance is not affected by concomitant doxapram therapy but shows a rapid maturation with postnatal age. As current guidelines do not adjust the caffeine dose with postnatal age, decreased exposure to caffeine might partly explain the need for doxapram therapy after the first week of life.

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Nutritional status of preterm neonates at discharge in sanglah hospital

International Journal of Health Sciences ◽

10.29332/ijhs.v4n3.449 ◽

2020 ◽

Vol 4 (3) ◽

pp. 10-19

Author(s):

I Made Samitha Wijaya ◽

Made Sukmawati ◽

Putu Junara Putra ◽

I Made Kardana ◽

I Wayan Dharma Artana

Keyword(s):

Weight Gain ◽

Birth Weight ◽

Breast Milk ◽

Low Birth Weight ◽

Nutritional Status ◽

Enteral Feeding ◽

Preterm Neonate ◽

Descriptive Study ◽

Preterm Neonates ◽

Neonatal Ward

The purpose of this study was to determine the nutritional status of preterm neonates when discharged from the hospital. A descriptive study was reviewed from the register of preterm neonate after hospitalization in neonatal ward Sanglah Hospital Denpasar. The number of total samples in this study was 190 patients. Most of the preterm neonates in this study were low birth weight (59.47%). At the beginning of the hospitalization, there were 83.86% preterm neonates with good nutritional status, decreased to 54.73% at discharge from the hospital. The group of neonates that had the highest number of decreases in the good nutritional status at discharge was found in 28-32 weeks gestational age. Most of the samples used breast milk for enteral feeding (68,42%). In preterm neonates with sepsis, only 42.52% neonates discharge with good nutritional status. Low birth weight preterm neonates with kangaroo method care were found increased weight gain in 78.57% neonates. The nutritional status of preterm neonates following hospitalization at Sanglah hospital is still not good. The preterm neonates with good nutritional status were decreased at discharge from the hospital.

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Antioxidant Effect of Melatonin in Preterm Newborns

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/6308255 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Lucia Marseglia ◽

Eloisa Gitto ◽

Elisa Laschi ◽

Maurizio Giordano ◽

Carmelo Romeo ◽

...

Keyword(s):

Oxidative Stress ◽

Placebo Group ◽

Free Radical ◽

Preterm Infants ◽

Plasma Concentrations ◽

Preterm Neonates ◽

Double Blind ◽

Blood Concentrations ◽

Melatonin Administration ◽

Preterm Newborns

Introduction. Preterm infants are at risk of free radical-mediated diseases from oxidative stress (OS) injury. Increased free radical generation has been demonstrated in preterm infants during the first seven days of life. Melatonin (MEL) is a powerful antioxidant and scavenger of free radicals. In preterm neonates, melatonin deficiency has been reported. Exogenous melatonin administration appears a promising strategy in the treatment of neonatal morbidities in which OS has a leading role. Objective. The aim was to evaluate plasma MEL concentrations and OS biomarkers in preterm newborns after early administration of melatonin. Methods. A prospective, randomized double-blind placebo-controlled pilot study was conducted from January 2019 to September 2020. Thirty-six preterm newborns were enrolled. Starting from the first day of life, 21 received a single dose of oral melatonin 0.5 mg/kg once a day, in the morning (MEL group); 15 newborns received an equivalent dose of placebo (placebo group). Samples of 0.2 mL of plasma were collected at 24 and 48 hours after MEL administration. Plasma concentrations of melatonin, non-protein-bound iron (NPBI), advanced oxidation protein products (AOPP), and F2-isoprostanes (F2-Isopr) were measured. Babies were clinically followed until discharge. Results. At 24 and 48 hours after MEL administration, the MEL concentrations were significantly higher in the MEL group than in the placebo group ( 52759.30 ± 63529.09 vs. 28.57 ± 46.24 pg/mL and 279397.6 ± 516344.2 vs. 38.50 ± 44.01 pg/mL, respectively). NPBI and AOPP did not show any statistically significant differences between the groups both at 24 and 48 hours. At 48 hours, the mean blood concentrations of F2-Isopr were significantly lower in the MEL group than in the placebo group ( 36.48 ± 33.85 pg/mL vs. 89.97 ± 52.01 pg/mL). Conclusions. Early melatonin administration in preterm newborns reduces lipid peroxidation in the first days of life showing a potential role to protect high-risk newborns. Trial Registration. This trial is registered with NCT04785183, Early Supplementation of Melatonin in Preterm Newborns: the Effects on Oxidative Stress.

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Prenatal Exposure to Perfluoroalkyl Substances and Birth Outcomes; An Updated Analysis from the Danish National Birth Cohort

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph15091832 ◽

2018 ◽

Vol 15 (9) ◽

pp. 1832 ◽

Cited By ~ 25

Author(s):

Qi Meng ◽

Kosuke Inoue ◽

Beate Ritz ◽

Jørn Olsen ◽

Zeyan Liew

Keyword(s):

Birth Weight ◽

Preterm Birth ◽

Low Birth Weight ◽

Birth Cohort ◽

Birth Outcomes ◽

Statistical Power ◽

Plasma Concentrations ◽

Fold Increase ◽

Perfluoroalkyl Substances ◽

Danish National Birth Cohort

Perfluoroalkyl substances (PFASs) are widespread industrial pollutants that are extremely persistent in the environment. A previous study in the Danish National Birth Cohort (DNBC) found prenatal perfluorooctanoate (PFOA) exposure was associated with decreased birth weight, but had insufficient statistical power to evaluate adverse birth outcomes. Here, we conducted additional analyses in three samples originating from the DNBC for 3535 mothers and infant pairs to evaluate associations between prenatal PFASs exposures and low birth weight and preterm birth. Maternal plasma concentrations were measured for six types of PFASs in early pregnancy. Several PFASs were associated with a reduction in birth weight and gestational age. We estimated a nearly 2-fold increase in risks of preterm birth for the higher quartiles of PFOA and perflourooctanesulfonate (PFOS) exposure. In spline models, risk of preterm birth was increased for perfluorononanoic acid (PFNA), perfluoroheptane sulfonate (PFHpS) and perfluorodecanoic acid (PFDA) in higher exposure ranges. We also observed some elevated risks for low birth weight but these estimates were less precise. Our findings strengthen the evidence that in-utero PFASs exposures affect fetal growth. Future studies are needed to evaluate whether these associations persist with the decline of PFOA and PFOS in populations and should also investigate newer types of fluorinated compounds introduced more recently.

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P24 Caffeine in preterm neonates: impact on sleep wake regulation

Archives of Disease in Childhood ◽

10.1136/archdischild-2019-esdppp.62 ◽

2019 ◽

Vol 104 (6) ◽

pp. e26.3-e27

Author(s):

AN Datta ◽

G Koch ◽

N Schönfeld ◽

K Jost ◽

A Atkinson ◽

...

Keyword(s):

Birth Weight ◽

Very Low Birth Weight ◽

Internal Clock ◽

Lower Percentage ◽

Preterm Neonates ◽

Quiet Sleep ◽

Caffeine Concentration ◽

Very Preterm ◽

Caffeine Citrate ◽

Apnea Of Prematurity

BackgroundSleep wake regulation undergoes distinctive maturational changes. Ultradian sleep wake rhythm predominates at preterm age and is mainly driven by the internal clock. Increased perinatal morbidity in preterm neonates often appears with breathing disorders, among which apnea of prematurity (AOP) is the most frequently observed. Pharmacological support with caffeine has been successfully employed in the treatment of AOP. Nowadays, caffeine citrate is administered to all preterm neonates suffering from AOP. Objective of our study was a quantitative investigation of whether caffeine citrate treatment for reduction of apnea and bradycardia of prematurity affects sleep-wake behavior in preterm neonates.MethodsObservational study of 64 preterm neonates during their first five days of life with gestational age (GA) < 32 weeks or very low birth weight of < 1500 g. Total of 52 patients treated with caffeine and 12 controls without caffeine were included. Sleep-wake behavior was scored in wakefulness (W), active sleep (AS), and quiet sleep (QS) associated with physical and cerebral regeneration. Individual caffeine concentration of every neonate was simulated with a pharmacokinetic model.ResultsFor increasing caffeine concentration, W increased, AS decreased, and QS was unchanged for GA > or = 28 weeks. No caffeine effect for GA < 28 weeks could be demonstrated. Maturational effects could be seen when comparing preterm neonates of GA >32 weeks with a birth weight of < 1500 g with very preterm neonates born of GA < 32: Neonates born >32 weeks had a significantly higher amount of W and lower percentage of AS.ConclusionsTreatment of apnea and bradycardia as well as stabilization of respiration with standard caffeine treatment is not at cost of QS, i.e. time for physical and cerebral regeneration during sleep remains unchanged. There is an increased fraction of W, alertness and most probably also arousability.Disclosure(s)Nothing to disclose

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Mortality of preterm neonates and its predictors in the Northwest part of Ethiopia: A retrospective cohort study

10.21203/rs.2.10832/v1 ◽

2019 ◽

Author(s):

Aklilu Endalamaw Sinshaw ◽

Biniam Minuye ◽

Bezatu Mengistie ◽

Abebaw Yeshambel ◽

Nega Assefa

Keyword(s):

Cohort Study ◽

Birth Weight ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Neonatal Mortality ◽

Retrospective Cohort ◽

Distress Syndrome ◽

Preterm Neonate ◽

Very Low Birth Weight ◽

Preterm Neonates

Abstract Abstract Background: Preterm birth is highly reported in some countries and disparities on survival rates of preterm neonate are escalating across countries. Providing adequate medical care during pregnancy and childbirth has been endorsed. However, neonatal mortality is continuing to be one of the sustainable development goals. To achieve this aim, data from the different geographical area is suggested. Objective: This study was aimed to assess mortality of preterm neonates and its predictors in the Northwest part of Ethiopia. Methods: Institution based retrospective cohort study was conducted among 535 preterm neonates. Data was entered into EPi-data 4.2.0.0 and transferred to STATA version 14 statistical software for analysis. Kaplan-Meier survival analysis and Log-rank test were used to see statistical differences between categories of variables. Cox proportional hazard model was used to identify independent predictors of preterm neonatal mortality. The proportional assumption test had been checked using the Schoenfeld residual test. Variables with p-value ≤ 0.05 were considered as predictors of preterm neonatal mortality. Results: In this study, 31.2% (95% CI: 27.3, 35.1) of preterm neonate were died. Preterm neonates with a gestational age of less than 32 weeks (AHR=1.74; 95%CI: 1.24, 2.46), being male sex (AHR=1.38; 95%CI: 1.01, 1.90), born from preeclampsia/ eclampsia mothers (AHR=1.95; 95%CI: 1.13, 3.36), being extremely very low birth weight (AHR=2.94; 95%CI: 1.05, 8.24), diagnosed with respiratory distress syndrome (AHR=1.70; 95%CI: 1.20, 2.41) were predictors of preterm death. Conclusion and Recommendations: Preterm neonatal mortality found to be high. Four neonatal and one maternal-related variable were recognized predictors of mortality in preterm neonates. The study suggests preventing and controlling preeclampsia/ eclampsia, especial care for neonates born with very low birth weight, born before 32 weeks of gestation, and diagnosed with respiratory distress syndrome are imperative. Keywords: Preterm, Neonate, Mortality, Ethiopia

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