Trends in neonatal morbidity and mortality for very low birthweight infants: a 20-year single-center experience.

OBJECTIVE: To describe trends in mortality and morbidity rates of very low birth weight infants as well as their pre-, peri- and postnatal characteristics over a period of 20 years' time. METHODS: Retrospective study in all very low birth weight infants admitted to the neonatal intensive care unit of the University Hospitals Ghent from 1 January 2000, to 31 December 2020. Mortality was the primary outcome variable with major morbidities being co-primary outcome variables. Pre-, peri- and postnatal characteristics are secondary outcome variables. We compared pre-, peri- and postnatal characteristics, as well as major morbidities between different groups with comparable rates of mortality. RESULTS: We included a total of 2037 very low birth weight infants and divided them in 3 epochs based on stepwise reductions in mortality in 2008 and 2013: 2000-2007 (n = 718), 2008-2012 (n = 506) and 2013-2020 (n = 813). Mortality decreased significantly over the years in all gestational ages, but predominantly in those with the youngest gestational age. Changes in obstetric and neonatal care were observed over time. Most significant changes were the increased use of antenatal corticosteroids, magnesium sulfate and surfactant. Intraventricular hemorrhage grade III/IV decreased significantly in all gestational ages. Significant increase in retinopathy of prematurity was observed. Bronchopulmonary dysplasia at 36 weeks and discharge home with oxygen is increasing in the total group. In those born below 26 weeks a slight increase in all major morbidities was observed especially of patent ductus arteriosus and retinopathy of prematurity. Increase of all other major morbidities seems to stabilize in epoch 3. The number of infants surviving without any major morbidity increases to almost 1/2 in all very low birth weight infants and to 1/10 in those born 24-25 weeks gestation. CONCLUSION: Analysis of the real-life experience showed that survival in very low birth weight infants significantly increased over time. Evolution of major morbidities will have to be carefully watched in the future.

Pregnancy termination at a viable stage in daily clinical practice: A nationwide mortality follow-back study in Flanders, Belgium.

OBJECTIVE: Congenital malformations are frequently diagnosed prenatally even at a viable stage. No adequate registration of incidence and characteristics of late termination of pregnancy (TOP) or abortion for medical reasons exists in Flanders. METHODS: Nationwide mortality follow-back survey sent to physicians signing death certificates of all stillbirths for 22 weeks gestation onward (September 2016-December 2017) in Flanders, Belgium. Questions measured whether late TOP preceded stillbirth, and which clinical and sociodemographic characteristics were indicated. Questionnaire data were linked with sociodemographic information from death certificates. RESULTS: Response rate was 56% (203/366). 38% of stillbirths (77/203) concerned late TOP. In 88.3% of late TOPs, physicians classified congenital anomalies of the foetus as serious or very serious (incompatibility with life outside the womb or severe neurological or physical impairment). In 26% of cases, late TOP was first suggested by the physician rather than spontaneously requested by parents (73%). 88% of late TOPs were discussed in open team meetings. CONCLUSIONS: 2/5 stillbirths were preceded by late TOP, indicating severe underreportation by existing registrations and a dire need for adequate registration methods. Although late TOP was most often explicitly requested by parents, in » cases termination was suggested first by physicians. Parents are sometimes hesitant to bring up late TOP themselves, indicating that TOP should always be counselled as an equivalent option.

Association of antenatal magnesium sulfate with reduced late-onset sepsis in extreme preterm infants.

OBJECTIVES: Neonatal intensive care has changed extensively over the last decades resulting in improved survival of extreme preterm infants. However, improved survival is associated with prolonged hospitalization, mechanical ventilation and use of invasive devices, which are all predisposing factors for LOS. LOS is known to increase short- and long-term morbidities resulting in impaired neurodevelopmental outcome. Besides treatment with antibiotics and supportive care, there is an unmet need for adjunctive therapies to prevent neonatal sepsis and hereby improve outcome. METHODS: In a retrospective single-center design, we explored underlying pre-, peri- and postnatal factors in extreme preterm infants with and without LOS to potentially identify future strategies in the prevention of LOS in these infants. RESULTS: Associations formerly published could be confirmed, such as lower birth weight, longer duration of respiratory support, parenteral nutrition and NICU stay and a higher incidence of almost all neonatal morbidities. A new interesting finding was the fact that infants with LOS received more antenatal magnesium sulfate (p = 0.002). After nearest neighbor matching based on birth weight, gestational age, gender and multiplicity increased duration of parenteral nutrition and NICU stay, the incidence of PVL remained significantly different between the two groups (LOS/no LOS), but also the association between antenatal magnesium sulfate administration and less LOS held true (p = 0.004). CONCLUSION: In this study, extreme preterm infants receiving antenatal magnesium sulfate developed less LOS. Whether this is merely an associative factor reflecting illness severity or an interesting link for new preventive strategies for LOS, should be further explored.

Suboptimal Beta-Lactam Therapy in Critically Ill Children: Risk Factors and Outcome.

OBJECTIVES: In critically ill children, severely altered pharmacokinetics may result in subtherapeutic ß-lactam antibiotic concentrations when standard pediatric dosing regimens are applied. However, it remains unclear how to recognize patients most at risk for suboptimal exposure and their outcome. This study aimed to: 1) describe target attainment for ß-lactam antibiotics in critically ill children, 2) identify risk factors for suboptimal exposure, and 3) study the association between target nonattainment and clinical outcome. DESIGN: Post hoc analysis of the "Antibiotic Dosing in Pediatric Intensive Care" study (NCT02456974, 2012-2019). Steady-state trough plasma concentrations were classified as therapeutic if greater than or equal to the minimum inhibitory concentration of the (suspected) pathogen. Factors associated with subtherapeutic concentrations and clinical outcome were identified by logistic regression analysis. SETTING: The pediatric and cardiac surgery ICU of a Belgian tertiary-care hospital. PATIENTS: One hundred fifty-seven patients (aged 1 mo to 15 yr) treated intravenously with amoxicillin-clavulanic acid, piperacillin-tazobactam, or meropenem. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three hundred eighty-two trough concentrations were obtained from 157 patients (median age, 1.25 yr; interquartile range, 0.4-4.2 yr). Subtherapeutic concentrations were measured in 39 of 60 (65%), 43 of 48 (90%), and 35 of 49 (71%) of patients treated with amoxicillin-clavulanic acid, piperacillin-tazobactam, and meropenem, respectively. Estimates of glomerular filtration rate (eGFR; 54% increase in odds for each sd increase in value, 95% CI, 0.287-0.736; p = 0.001) and the absence of vasopressor treatment (2.8-fold greater odds, 95% CI, 1.079-7.253; p = 0.034) were independently associated with target nonattainment. We failed to identify an association between antibiotic concentrations and clinical failure. CONCLUSIONS: Subtherapeutic ß-lactam concentrations are common in critically ill children and correlate with renal function. eGFR equations may be helpful in identifying patients who may require higher dosing. Future studies should focus on the impact of subtherapeutic concentrations on clinical outcome.

Cranial ultrasound and MRI: complementary or not in the diagnostic assessment of children with congenital CMV infection?

Whether or not cranial ultrasound (crUS) and cerebral magnetic resonance imaging (MRI) have both a place in the assessment of children with congenital cytomegalovirus infection (cCMV) remains a topic of discussion between research groups. Literature suggests that MRI is indicated only in children with abnormal crUS.In Flanders, Belgium, combined crUS and MRI was performed on 639 children with cCMV, referred for diagnostic assessment. Cranial US was classified as abnormal in the presence of striatal vasculopathy, calcifications, cysts, cystic germinolysis, and/or ventriculomegaly. MRI findings were classified as abnormal in the presence of gyration disorders, cerebellar abnormalities, ventriculomegaly, cysts, or pathologic white matter lesions.One in five children (93/480) with normal crUS showed abnormal findings on MRI. Of them, 85 (91.4%) were classified as symptomatic. In 37 of those 93 children (39.8%), classification as severely symptomatic was made based on MRI lesions alone. MRI and crUS proved to be complementary in the assessment of CNS involvement in children with cCMV. Long-term studies are needed to evaluate the importance of this finding with respect to outcome and benefit of therapy in this particular subgroup of patients with cCMV infection.Conclusion: Our findings support an enhanced role of MRI in the diagnosis of CNS involvement in children with cCMV infection. The ideal assessment should include both imaging techniques, as the strengths of each test compensate for the other's weaknesses. What is Known: • Congenital CMV infection involves the central nervous system with direct injury to and possible disruption of brain development. • Experts suggest that MRI is indicated only in children with abnormal crUS. What is New: • In almost 20% of our children with a normal cranial ultrasound, abnormalities were detected on MRI. • Our results suggest that performing both MRI and cranial US is important to obtain a complete assessment of central nervous system involvement in children with cCMV.

Variation in vancomycin dosing and therapeutic drug monitoring practices in neonatal intensive care units.

Background Vancomycin is a frequently used antibiotic in neonates. However, there is no consensus guideline on the optimal dosing regimen and therapeutic drug monitoring (TDM) practices in this patient population. Objective To document the variability in the current dosing and TDM practices in neonatal intensive care units (NICU). Setting Belgian and Dutch NICUs. Method An online questionnaire was disseminated by e-mail to potential respondents. Main outcome measure Differences in vancomycin dosing and TDM practices in comparison with a reference source, the Dutch Paediatric Formulary. Results Eighteen NICUs (response rate 62%) participated. Eleven different dosing regimens are applied, with 83% using intermittent dosing regimens. Stratifying covariates used to determine the (initial) dosage include gestational age, postnatal age, serum creatinine, concurrent use of non-steroidal anti-inflammatory drugs, birth weight and current weight. Large variability is observed with regard to TDM practice as well, both for the concentration target range and the times of (re)sampling. Dosing calculators are more commonly used in the Netherlands than Belgium. Conclusion Significant inter-centre variability in dosing and TDM practices was found. The development of international consensus guidelines is required to optimize therapy. Dosing calculators to guide dosing are not yet considered as part of standard-of-care.

Vancomycin dosing and therapeutic drug monitoring practices: guidelines versus real-life.

Background Correct dosing and therapeutic drug monitoring (TDM) practices are essential when aiming for optimal vancomycin treatment. Objective To assess target attainment after initial dosing and dose adjustments, and to determine compliance to dosing and TDM guidelines. Setting Tertiary care university hospital in Belgium. Method A chart review was performed in 150 patients, ranging from preterm infants to adults, treated intravenously with vancomycin. Patient characteristics, dosing and TDM data were compared to evidence-based hospital guidelines. Main outcome measures Target attainment of vancomycin after initial dosing and dose adjustments. Results Subtherapeutic concentrations were measured in 68% of adults, in 76% of children and in 52% of neonates after treatment initiation. Multiple dose adaptations (median 2, Q1 1-Q3 2) were required for target attainment, whilst more than 20% of children and neonates never reached targeted concentrations. Regarding compliance to the hospital guideline, some points of improvement were identified: omitted dose adjustment in adults with decreased renal function (53%), delayed sampling (16% in adults, 31% in children) and redundant sampling (34% of all samples in adults, 12% in children, 13% in neonates). Conclusion Target attainment for vancomycin with current dosing regimens and TDM is poor in all age groups. Besides, human factors should not be ignored when aiming for optimal treatment. This study reflects an ongoing challenge in clinical practice and highlights the need for optimization of vancomycin dosing strategies and improvement of awareness of all health care professionals involved.

Parental perspectives long term after neonatal clinical trial participation: a survey.

BACKGROUND: Although recruiting newborns is ethically challenging, clinical trials remain essential to improve neonatal care. There is a lack of empirical data on the parental perspectives following participation of their neonate in a clinical trial, especially at long term. The objective of this study is to assess experiences and emotions of parents, long term after trial participation in an interventional drug trial. METHODS: Parents of former participants of five neonatal interventional drug trials were surveyed at long term (3-13 years ago) after participation. The survey assessed parental contentment with trial participation, perceived influence of the trial on care and health, emotional consequences of participation, and awareness of typical clinical trial characteristics on 6-point Likert scales. RESULTS: Complete responses were received from 123 parents (52% of involved families). Twenty percent of parents did not remember participation. Those who remembered participation reported high contentment with overall trial participation (median 5.00), but not with follow-up (median 3.00). Most parents did not perceive any influence of the trial on care (median 2.00) and health (median 2.43). Almost all parents reported satisfaction and pride (median 4.40), while a minority of parents reported anxiety and stress (median 1.44) or guilt (median 1.33) related to trial participation. A relevant minority was unaware of typical trial characteristics (median 4.20; 27% being unaware). CONCLUSIONS: Overall, parents reported positive experiences and little emotional distress long term after participation. Future efforts to improve the practice of neonatal clinical trials should focus on ensuring effective communication about the concept and characteristics of a clinical trial during consent discussions and on the follow-up after the trial.

Transient hypothyroidism associated with viral Human Parechovirus encephalitis in a newborn.

Human Parechovirus type 3 (HPeV-3) is a neurotropic virus which can cause neonatal encephalitis, presenting as encephalopathy with seizures and diffuse white matter lesions on brain imaging. Neurodevelopmental outcome is linked to the extent of white matter abnormalities. We report on a neonate with clinical and biochemical findings of transient central hypothyroidism associated with HPeV-3 encephalitis. The co-occurrence of transient hypothyroidism and viral encephalitis has not been reported in newborns before. Transient suppression of the hypothalamo-pituitary-thyroidal axis is described in critically ill babies as the nonthyroidal-illness syndrome. Assessment of thyroid function in neonatal cases of HPeV-3 infection is required to conclude whether a transient hypothyroidism as in nonthyroidal-illness syndrome may be triggered by viral meningo-encephalitis and if treatment may influence neurodevelopmental outcome.

Relationship between insulin-like growth factor I levels, early insulin treatment, and clinical outcomes of very low birth weight infants.

OBJECTIVES: Insulin regulates the secretion of insulin-like growth factor I (IGF-I) in the newborn, and low levels of IGF-I have been linked to neonatal morbidity. As part of the Neonatal Insulin Replacement Therapy in Europe Trial, we investigated the impact of early insulin treatment on IGF-I levels and their relationship with morbidity and growth. STUDY DESIGN: Prospective cohort analyses of data collected as part of an international randomized controlled trial. Blood samples (days 1, 3, 7, and 28), were taken for IGF-I bioassay from 283 very low birth weight infants (<1500 g). RESULTS: Early insulin treatment led to a late increase in IGF-I levels between day 7 and 28 (P = .028). In the first week of life IGF-I levels were lower in infants with early hyperglycemia; mean difference -0.10 µg/L (95% CI -0.19, -0.02, P = .02). Lower levels of IGF-I at day 28 were independently associated with an increased risk of chronic lung disease, OR 3.23 (95% CI, 1.09-9.10), and greater IGF-I levels were independently associated with better weight gain, 0.10 kg (95% CI, 0.03-0.33, P = .02). CONCLUSIONS: Early intervention with insulin is related to increased IGF-I levels at 28 days. Low IGF-I levels are associated with hyperglycemia, increased morbidity, and reduced growth. Increasing IGF-I levels may improve outcomes of very low birth weight infants.

Low but inducible contribution of renal elimination to clearance of propylene glycol in preterm and term neonates.

BACKGROUND: Despite limited information being available on the pharmacokinetics of excipients, propylene glycol (PG) is often used as an excipient in both adults and children. The aim of this study is to characterize the renal and hepatic elimination of PG in preterm and term neonates. METHODS: The pharmacokinetic analysis of PG was performed in NONMEM 6.2. on the basis of PG concentrations in plasma and/or urine samples for a total of 69 (pre)term neonates (birth weight 630-3980 g, gestational age 24-41 weeks, postnatal age 1-29 days) who received PG coadministered with intravenous paracetamol (5-10 mg/kg per 6 hours), phenobarbital (5 mg·kg(-1)·d(-1)), or both. To capture the time-dependent trend in the renal excretion of PG, different models based on time after the first dose, urine volume, and creatinine amount in urine were tested. RESULTS: A one-compartment model parameterized in terms of renal clearance, hepatic clearance, and volume of distribution was found to adequately describe the observations in both plasma and urine. After the first dose was administered, the renal elimination of PG was 15% of total clearance, which increased over time to 25% at 24 hours after the first dose of PG. This increase was best described using a hyperbolic function based on time after the first dose. CONCLUSIONS: Renal elimination of PG in (pre)term neonates is low, particularly compared with the reported percentage of 45% in adults, but it may increase with time after the first dose of PG. To study whether this increase is caused by an autoinduced increase in the renal secretion or a reduction of tubular reabsorption of PG, further research is needed.

Association between retinal neovascularization and serial weight measurements in murine and human newborns.

INTRODUCTION: Retinopathy of prematurity (ROP) is a leading cause of preventable blindness throughout the world. Several risk factors have been studied, but most studies remain inconclusive. Evidence is accumulating that one of the strongest predictors of ROP, in addition to oxygen use and low gestational age, is poor weight gain during the first postnatal weeks.
 METHODS: In a prospective study, we sought to determine the importance of serial weight measurements to help predict neovascularization (NV). In a first stage, a summary of the response in each case is identified and calculated as area under the curve (AUC). In a second stage, these different AUCs are analyzed by nonparametric Mann-Whitney U test. For the murine study, pups were redistributed in smaller and larger litters. On postnatal day (P)7-12, the oxygen-induced retinopathy (OIR) model was applied. Body weight was measured on P7, P14, and P17. Retinal NV was assessed on P17. For the human study, the subjects were part of the control arm of the NIRTURE trial. Ophthalmologists screened for ROP. Birthweight was recorded. Weekly weight measurements were performed for the first 4 weeks.
 RESULTS: The AUC of serial weight (gain) measurements was significantly lower in murine (14 vs 17 g; p = 0.01) and human (140 g/wk vs 240 g/wk; p = 0.0001) newborns developing retinal NV.
 CONCLUSION: This prospective study supports previous findings, using a new way of statistical analysis, that early postnatal weight gain is an important indicator in the development of neovascular disease.

The paracetamol concentration-effect relation in neonates.

OBJECTIVES: We suggested a loading dose (20 mg · kg(-1) ) followed by 10 mg · kg(-1) q6h of intravenous (IV) paracetamol to achieve an effect compartment concentration of 11 mg · l(-1) in neonates. Since there are no pharmacodynamic data to support such an effect compartment concentration, pain scores collected in neonates treated with an IV paracetamol loading dose (20 mg · kg(-1) ) were used to validate this effect compartment concentration. METHODS: Pain scores (Leuven Neonatal Pain Score, LNPS, 0-14) before and 0.5, 1, 2, 3, 4, 5, and 6 h after IV paracetamol loading dose administration in neonates to whom IV paracetamol was administered as single analgesic (PARANEO, www.clinicaltrials.gov, NCT00969176) were collected. Trends were analyzed using repeated measures anova. An E(max) model with a delayed response compartment was fitted to data using population modeling. RESULTS: Nineteen of 60 neonates included in the PARANEO study received monotherapy with IV paracetamol to treat mild to moderate pain (e.g., alprostadil administration, delivery related trauma). Using repeated measures anova, there was a trend (P = 0.02) for lower pain scores within 30 min after administration, with a slight increase in pain scores from 5 to 6 h. An E(max) model had a maximum effect of 4.15 pain units, an EC(50) of 2.07 mg · l(-1). Equilibration halftime (T(1/2) keo) was 1.58 h. CONCLUSION: Intravenous paracetamol is effective for moderate pain. An effect compartment concentration of 10 mg · l(-1) (loading dose of 20 mg · kg(-1) ) is associated with a pain score reduction of 3.4 LNPS units. This analysis suggests a similar paracetamol effect compartment concentration in neonates compared to children.

Multidetector CT of right-sided congenital diaphragmatic hernia associated with hepatopulmonary fusion in a newborn.

We present a neonate with a complex congenital cardiopathy and a right-sided diaphragmatic hernia complicated with hepatopulmonary fusion. Radiography, abdominal US and multidetector CT (MDCT) demonstrated right-sided lung hypoplasia and liver herniation. In addition, MDCT angiography showed abnormal pulmonary vascular anatomy. At surgery, a right-sided diaphragmatic hernia with a partially herniated liver and hepatopulmonary fusion was confirmed. There was no aberrant systemic vascular supply towards the lower lobe, as seen in extralobar sequestration. MDCT angiography of the chest and upper abdomen with optimal enhancement and reconstruction of the pulmonary and hepatic vasculature can demonstrate associated anomalies in cases of suspected primary or secondary right lung hypoplasia.

Continuous glucose monitoring and retinopathy of prematurity.

PURPOSE: To use the continuous glucose monitoring system (CGMS) in very low birthweight (VLBW) infants to further explore the association between elevated glucose levels and retinopathy of prematurity (ROP) and to find new preventive strategies for ROP. METHODS: A secondary analysis of risk factors for ROP in VLBW infants was performed in the neonatal intensive care units of University Hospital Leuven and ZOL Genk, Belgium. The subjects were part of the NIRTURE trial (ISRCTN78428828). Only control subjects with conclusive ROP assessments who received standard clinical care were included in this analysis. A total of 100 VLBW infants (birthweight = 1500 g) were included. Twenty-three (23%) infants developed ROP; 77 (77%) did not. RESULTS: Development of ROP was linked to the known classic risk factors. In addition, ROP was associated with higher glycemia levels across the first week (p between 0.01 and <0.0001). Across the first week, glycemia predicted ROP with receiver operating characteristic (ROC) scores between 0.67 and 0.80, and with a median glycemia cutoff of 6.7 mmol/L. Comparison of ROC curves revealed first-week glycemia as an important variable in the development of ROP with a predictive power as high as the classic risk factors. CONCLUSIONS: Moderately elevated glucose levels in the first week of life are associated with the development of ROP. They contribute to this multifactorial disease in a way equal to the known classical risk factors for ROP. Therefore, careful monitoring of glucose levels by CGMS can be helpful in the prevention of ROP.

Prospective assessment of short-term propylene glycol tolerance in neonates.

INTRODUCTION: Propylene glycol (PG) is an unintentional frequently administered solvent in neonates despite the fact that PG accumulation potentially results in hyperosmolarity, lactic acidosis and renal/hepatic toxicity. METHODS: Prospective evaluation of renal (diuresis, creatinaemia, sodium), metabolic (base excess, anion gap, lactate, bicarbonate) and hepatic (alanine transaminase, aspartate aminotransferase, direct bilirubinaemia) tolerance to PG in (pre)term neonates following intravenous administration of formulations (paracetamol, phenobarbital, digoxin) that contain PG. Observations from 48 h before up to 48 after the last PG administration were described and compared (paired analysis). Clinical characteristics and observations collected following intravenous PG-paracetamol administration were compared with a historical cohort of neonates in whom similar (renal, hepatic) observations during exposure to a mannitol-containing paracetamol formulation were collected. RESULTS: 5566 observations were collected in 69 neonates before, during and following median PG exposure of 34 mg/kg/24 h (range 14-252). Progressive postnatal adaptation in renal, metabolic and hepatic function was documented, unrelated to the PG exposure. In the subgroup of 40 cases treated with intravenous PG-paracetamol, observations on renal and hepatic function were similar to a historical cohort of published observations following exposure to intravenous mannitol-paracetamol. CONCLUSIONS: Unintended PG administration (34 mg/kg/24 h) for a maximum of 48 h seems to be tolerated in (pre)term neonates and does not affect short-term postnatal adaptations. Further studies on PG disposition and the level of safe exposure to PG, including long-term safety data in neonates are needed.

Prevalence and determinants of hyperglycemia in very low birth weight infants: cohort analyses of the NIRTURE study.

OBJECTIVES: To investigate the prevalence and determinants of hyperglycemia in the preterm population, as part of the Neonatal Insulin Therapy in Europe (NIRTURE) Trial. STUDY DESIGN: We conducted prospective cohort analyses of continuous glucose monitoring data from control infants participating in an international randomized controlled trial. Data were collected from 188 very low birth weight infants (<1500 g). RESULTS: In the first week of life, 80% of infants had evidence of glucose levels >8 mmol/L, and 32% had glucose levels >10 mmol/L >10% of the time. Independent risk factors for hyperglycemia included increasing prematurity, small size at birth, use of inotropes, lipid infusions, and sepsis. There was a lack of association between rate of dextrose infused and risk of hyperglycemia. CONCLUSION: The prevalence of hyperglycemia in the very low birth weight infant is high, with marked variability in prevalence between infants, not simply related to rates of glucose infused, but to other potentially modifiable risk factors.

The effect of glycaemia on the cerebral oxygenation in very low birthweight infants as measured by near-infrared spectroscopy.

The cerebral tissue oxygenation index (TOI) and fractional tissue oxygen extraction (FTOE) reflect the cerebral oxygenation. We studied the effect of glycaemia on the TOI and FTOE, as measured by near-infrared-spectroscopy (NIRS). We continuously measured TOI, glycaemia, mean arterial blood pressure (MABP), saturation (SaO(2)) and transcutaneous carbon dioxide pressure (tPCO(2)) for at least 4 h during the first week of life in neonates with gestational age (GA) < 32 weeks and weight < 1500 g. FTOE was calculated. 24 measurements in 11 neonates were analyzed. We found a significant negative correlation (r = -0.077; p = 0.0344) between glycaemia and TOI, also after correction for MABP, SaO(2) and tPCO(2) (r = -0.118; p = 0.002) and a significant positive correlation between glycaemia and FTOE (r = 0.147; p < 0.000) which remained significant after correction for MABP and tPCO(2) (r = 0.116; p = 0.001). Our results indicate that in neonates during the first days of life glycaemia - even within the normal ranges and after correction for MABP, SaO(2) and tPCO(2) - influences the cerebral oxygenation.

In vivo glucuronidation activity of drugs in neonates: extensive interindividual variability despite their young age.

Compared with phase I isoenzymes, data on isoenzyme-specific phenotypic activity of uridine diphosphate glucuronosyltransferase (UGT) and its covariates in neonates are limited. In vivo observations on morphine, paracetamol (acetaminophen), and propofol disposition throughout childhood confirm the overall low-glucuronidation activity in neonates observed in in vitro studies. In addition to the phenotypic low-glucuronidation activity, in vivo observations of bilirubin (UGT1A1), morphine (UGT2B7), paracetamol (UGT1A6), and propofol (UGT1A9) glucuronidation in neonates display extensive interindividual variability, only in part explained by postmenstrual and postnatal age. Covariates like disease state characteristics (decreased morphine metabolism during therapeutic head cooling), genetic polymorphisms (UGT1A1 genetic variants and differences in bilirubin metabolism), or environmental factors (increased urinary excretion of paracetamol-glucuronide by repeated administration of paracetamol) further contribute to this variability. A focused approach to unveil covariates of the interindividual range is needed to improve our knowledge on drug disposition in early life.

Cardiorespiratory depression and hyperglycemia after unintentional ingestion of brimonidine in a neonate.

PURPOSE: Brimonidine is a third-generation selective alpha-2 adrenergic agonist that lowers intraocular pressure by decreasing aqueous humor production and increasing uveoscleral flow. Its safety profile for children <2 years of age remains unknown. METHODS: We describe a case of ingestion of a single drop of brimonidine 0.2% in a newborn, resulting in sedation, cardiorespiratory depression, and hyperglycemia within minutes. CONCLUSIONS: This report adds to the existing evidence that brimonidine can have serious adverse side effects and should therefore be used with extreme caution in infants <2 years of age. Additionally,safety procedures like double-checking should also include vitamins or oral supplements to improve medication safety in the neonatal intensive care unit.