Biomedical subjects

Hugo Devlieger

Publications and source records attributed to Hugo Devlieger.

At least 19 recordsLinked to original sources

PubMed2006

Two female siblings with congenital heart disease, postaxial polydactyly, ectopic neuropituitary gland, hair anomalies and characteristic facial features: a new syndrome?

We present two siblings from unrelated parents presenting with intrauterine growth retardation, a congenital heart defect, postaxial polydactyly, a brain malformation (ectopic neuropituitary gland associated with a hypoplastic adenopituitary in one of them, and a hypoplastic cerebellum and vermis in the other), abnormal hair with temporal balding, a striking facial dysmorphism and, at least in the child who survived, postnatal growth retardation and severe developmental delay. This probably represents a novel syndrome.

Choristoma↗

PubMed2006

Dopamine is not an independent risk factor for reduced amikacin clearance in extremely low-birth-weight infants.

INTRODUCTION: Important inter-individual variability in amikacin clearance was observed in preterm infants, only in part explained by gestational age (GA), birth weight, or coadministration of nonselective cyclo-oxygenase (COX) inhibitor. We therefore evaluated whether dopamine had an additional effect on amikacin clearance. METHODS: Clinical characteristics (GA, weight, COX inhibitor, dopamine, prenatal betamethasone) and amikacin pharmacokinetics were retrospectively collected in a cohort of preterm infants (GA of <31 wks, early neonatal life on respiratory support, between January 1, 1999 and January 6, 2005). Pharmacokinetics were calculated by assuming a one-compartment model with instantaneous input and first-order output based on paired samples collected for therapeutic drug monitoring before and following second administration. Monovariate analysis (Spearman, Mann-Whitney U test) was used to study the impact of clinical characteristics on amikacin clearance, and logistic regression was used to assess their potential independent effect. RESULTS: Paired amikacin samples were available for 240 neonates (mean GA, 28 wks; birth weight, 1042 g). Amikacin clearance was 0.46 (range, 0.09-2.33) mL/kg/min and distribution volume was 0.54 (range, 0.17-2.31) L/kg. GA, birth weight, COX inhibitor, and dopamine had a significant effect on amikacin clearance. In a logistic regression model, dopamine was no longer a significant variable when GA, birth weight, or cotreatment of a nonselective COX inhibitor was entered as second variable. CONCLUSIONS: Dopamine is an indicator but not an independent marker of reduced amikacin clearance in early neonatal life in extremely low-birth-weight infants. Therefore, neither dose nor interval should be adapted when dopamine is prescribed, if GA and coadministration of nonselective COX inhibitors already have been taken into account.

Amikacin↗

PubMed2005

Massive lung collapse with partial resolution after several years: a case report.

BACKGROUND: Bronchitis obliterans is a severe and extremely rare complication of respiratory tract infections in children and is characterized by massive atelectasis and collapse of the affected lung. Of the rare cases reported in the literature all surviving children underwent surgical resection of the collapsed lung. CASE PRESENTATION: We report an infant with bronchitis obliterans that was treated conservatively. 5 years after the initial event, partial lung re-expansion was documented. CONCLUSION: This case therefore supports a conservative treatment whenever possible with pneumonectomy only as a last treatment option.

Bronchiolitis Obliterans↗

PubMed2005

Nonselective cyclo-oxygenase inhibitors and glomerular filtration rate in preterm neonates.

The adverse effects of nonselective cyclo-oxygenase (COX) inhibitors on the immature kidney have been described in newborn rabbits, but it is much more laborious and difficult to study its relative impact on renal function in human neonates. Amikacin clearance was therefore used as surrogate marker to study the impact of nonselective COX-inhibitors on glomerular filtration rate. Clinical characteristics and amikacin clearance of infants on respiratory support were retrospectively collected. Results in neonates in whom either ibuprofen-lysine or acetylsalicylic acid was administered prophylactically to induce closure of a patent asymptomatic ductus arteriosus were compared to infants not cotreated with any COX-inhibitor (Mann-Whitney U-, chi-square tests). Amikacin clearance was calculated in 142 infants, of whom 50 were cotreated with ibuprofen and 33 with acetylsalicylic acid. There were no significant differences in clinical characteristics between the three groups. Compared to controls (0.52, range 0.09-2.33 ml/kg/min), a significant similar decrease in amikacin clearance in infants cotreated with ibuprofen (0.38, range 0.13-0.80 ml/kg/min, p<0.01) or acetylsalicylic acid (0.38, range 0.13-0.78 ml/kg/min, p<0.01) was demonstrated. Using amikacin clearance as marker, a significant and similar reduction in glomerular filtration rate was documented in preterm infants cotreated with ibuprofen or acetylsalicylic acid.

Amikacin↗

PubMed2005

Pharmacodynamics of chloral hydrate in former preterm infants.

UNLABELLED: The aim of this study was to document the pharmacodynamics of chloral hydrate in former preterm infants at term post-conception age. The degree of sedation (COMFORT), feeding behaviour and cardiorespiratory events (bradycardic events, apnoeas) before and after administration of chloral hydrate (oral, 30 mg/kg) were prospectively evaluated in former preterm infants during procedural sedation. Characteristics at birth, during neonatal stay and at inclusion were collected. Paired Wilcoxon and McNemar tests were used to study the impact of chloral hydrate. Characteristics of infants who displayed severe bradycardic events were compared to infants in whom no bradycardic events were recorded (Mann Whitney U, Fischer's exact). A significant increase in sedation (decrease COMFORT scale) was observed up to 12 h after administration. There was a minor but significant decrease in oral intake (161 to 156 ml/kg/day, P < 0.01). A significant increase in the number of bradycardic events (<80/min: 38 to 82 events, of which < 70/min: 30 to 79 of which < 60/min: 15 to 45; at least P < 0.01) and in the duration of the most severe bradycardic event (8-12.5 s) was observed. Therefore, further inclusion was stopped when 26 neonates were included. Infants who displayed severe bradycardic (< 60/min) events ( n = 13) after administration of chloral hydrate had a lower gestational age at birth without difference in post-conception age at inclusion. CONCLUSION: Chloral hydrate was associated with an increase in unintended side-effects in former preterm infants, likely reflecting population specific pharmacodynamics and kinetics of chloral hydrate.

Administration, Oral↗

PubMed2005

The impact of ibuprofen on renal clearance in preterm infants is independent of the gestational age.

The aim of this investigation was to evaluate whether the relative change in renal clearance due to ibuprofen administration depends on the gestational age (GA). Clearance of amikacin was used as a surrogate marker for renal clearance in preterm infants (GA 24-34 weeks, day 1) on respiratory support. Clearance in infants co-treated with ibuprofen was compared to that of infants not co-treated with ibuprofen. Absolute change of clearance in four consecutive cohorts of increasing (<27, 27-28, 29-31, 32-34 weeks) GA and linear correlations of clearance on GA were calculated in both groups. Data were collected from 204 infants, of whom 93 were co-treated with ibuprofen. Mean amikacin clearance was lower (0.48 to 0.59 ml/kg/min, P <0.001) in infants co-treated with ibuprofen. Absolute decrease in mean amikacin clearance (0.10 to 0.14 ml/kg/min) was similar in all four cohorts. Linear correlations of clearance with GA were documented in infants co-treated (y =0.21+0.011x) or not co-treated (y =0.44+0.009x) with ibuprofen. Renal clearance, reflected by amikacin clearance, is decreased by ibuprofen in preterm infants of 24 to 34 weeks GA on respiratory support on the 1st day of life, independent of the GA.

Amikacin↗

PubMed2005

Tight skin and limited joint movements as early presentation of Hutchinson-Gilford progeria in a 7-week-old infant.

UNLABELLED: We present a 7-week-old male infant with pseudoscleroderma as a primary manifestation of the Hutchinson-Gilford syndrome of premature aging. He had suffered intra-uterine growth retardation; micrognathism and a cleft palate were evident at birth. He presented with feeding difficulties and severe, diffuse scleroderma-like lesions, a faint peri-oral cyanosis and prominent scalp veins. With time, special facial features became more and more apparent: frontal bossing, prominent eyes, thin and fine nose and lips, microstomia, low-set ears and occipito-parietal alopecia. Histopathology of the skin showed an increased density and thickness of collagen in the dermis and hypodermis. Within the 1st year of life, typical skeletal characteristics were observed. The diagnosis of Hutchinson-Gilford syndrome was confirmed by analysis of the lamin A gene, revealing a heterozygous c.1824C > T (G608G) mutation. CONCLUSION: Hutchinson-Gilford syndrome is an extremely rare disorder of which the full clinical spectrum becomes evident with time. Sclerodermatous changes in the infant can be the first manifestation.

Alopecia↗

PubMed2005

Social inequalities in perinatal and infant mortality in the northern region of Belgium (the Flanders).

BACKGROUND: The study was intended to analyse the independent effect of some facets of the socio-economic status of both parents on perinatal, neonatal and post-neonatal mortality in the northern region of Belgium (the Flanders). METHOD: Perinatal data collected by the Study Centre for Perinatal Epidemiology were linked with socio-economic data collected by the district council. Mothers aged > or =25 years are included in the study. RESULTS: 50796 births were analysed. 452 infants died either before birth or during the first year of life. 52% of the foeto-infantile mortality occurred before birth and 57% of the infant mortality in the first week of life. The educational level was strongly related to foetal (p<0.001) and, to a lesser degree, to early-neonatal mortality (p=0.001). Employment did not correlate with any mortality item. Except for foetal mortality, the strongest correlation was always observed for maternal rather than paternal social items. In a logistic regression model, foetal mortality, perinatal mortality and infantile mortality remained strongly correlated with the educational level of the mother. Infant mortality beyond the first week of life was not correlated with any aspect of the social status of the parents. CONCLUSIONS: The educational level of the mother is the single most important determinant of infantile mortality in the Flanders representing the totality of hospital births by mothers aged > or =25 years in 1999 in the Flanders. KEY POINTS STUDY QUESTION: Does education, profession and actual employment of both parents, independently operates discrimination in the outcome of pregnancy up to one year? Results: Maternal education is the only significant and independent determinant of foetal as well as neonatal and foeto-infantile mortality. Results: The status of the mother is by far more important than that of the father in determining the outcome of pregnancy.

Belgium↗

PubMed2005

Intra- and interindividual variability of glucuronidation of paracetamol during repeated administration of propacetamol in neonates.

BACKGROUND: Major changes in drug clearance and metabolism are observed during infancy, in part based on ontogenic regulation of various metabolic pathways. Since paracetamol provides a good substrate to study UGT (1A6) activity, urinary metabolites of propacetamol were determined in neonates in whom propacetamol was repeatedly administered. METHODS: Paracetamol glucuronide (APAP-G), paracetamol sulphate (APAP-S) and free paracetamol were determined in urine samples of neonates during repeated administration of propacetamol. Spearman rank and linear multiple regression (MedCalc, Mariakerke, Belgium) were used to study the effect of postnatal age, of postconceptional age and of repeated administration on the relative contribution of APAP-G to overall urine paracetamol (APAP-G+APAP-S+free paracetamol) elimination (G/T ratio). RESULTS: 147 samples were collected in 23 neonates. Molar median G/T ratio was 14% (range 1-53). Besides increasing G/T ratio with increasing postnatal (p<0.0001) and postconceptional age (p<0.01), repeated administration (p<0.01) also correlated with an increasing G/T ratio, and repeated administration remained significant (p<0.01) after correction of postnatal and postconceptional age in a multiple regression model. CONCLUSION: Major variability in the ontogeny of UGT activity to overall elimination of paracetamol was documented in neonates. Besides postnatal and postconceptional age, a significant effect of repeated administration on UGT activity was documented.

Acetaminophen↗

PubMed2005

Fatal family outbreak of Bacillus cereus-associated food poisoning.

Bacillus cereus is a well-known cause of food-borne illness, but infection with this organism is not commonly reported because of its usually mild symptoms. A fatal case due to liver failure after the consumption of pasta salad is described and demonstrates the possible severity of the emetic syndrome.

Adolescent↗

PubMed2005

Variability in pain expression characteristics in former preterm infants.

OBJECTIVES: To document pain expression characteristics in former preterm infants in the first year of life in whom systematic evaluation and treatment of pain was provided. METHODS: Data on the Modified Behavioral Pain Scale (MBPS), Visual Analogue Scale (VAS, crying time and heart rate were collected during immunization. The effect of clinical characteristics {postconception and gestational age [PCA], surgery, ventilation, fentanyl, length of stay (LOS)} on bio-behavioral parameters was evaluated. RESULTS: 121 procedures were recorded in 49 infants. GA was 28 (25-32) weeks. PCA was 60 (34-90) weeks. Median MBPS was 8 (2-10), median crying time 44 (0-112) s. Median pre-procedural heart rate was 144 (103-201) and increased to 184 (147-220) afterwards, resulting in a relative increase of 29 (5-99)%. Median VAS score was 7 (1-10). Significant correlations of PCA with pre-procedural heart rate (r=-0.36) and with relative increase in heart rate (r=0.33) were identified. A correlation of LOS on crying time (r=0.37) was observed. CONCLUSIONS: Correlations of PCA with pre-procedural and relative increase in heart rate reflect the maturational decrease in heart rate. LOS had an effect on pain expression, potentially reflecting the impact of cumulative 'minor' procedural pain.

Analgesia↗

PubMed2004

Measurement of the liver tissue oxygenation by near-infrared spectroscopy.

OBJECTIVE: To study the relation between the liver tissue oxygenation index (TOI), transcutaneously measured with spatially resolved spectroscopy (a new method of near-infrared spectroscopy or NIRS), the mixed venous oxygen saturation and the blood flow in the different parts of the splanchnic circulation in newborn piglets. DESIGN: Tissue oxygenation index of the liver was measured in six newborn piglets at 33 degrees C, 35 degrees C, 37 degrees C and after a decrease in arterial carbon dioxide pressure (PaCO(2)). MEASUREMENTS: Mixed venous oxygen saturation, blood gas analysis and peripheral oxygen saturation were measured at each step. Gastric, proximal jejunal, midgut, distal ileal, splenic and hepatic arterial blood flow were measured by injection of coloured microspheres into the left atrium. NIRS optodes were attached to the skin over the liver and TOI was calculated. RESULTS: No significant changes of TOI of the liver were seen during the increase in temperature or change in PaCO(2). TOI correlated well with mixed venous oxygen saturation (r=0.85), the mid-ileal blood flow (r=0.57) and the distal ileal blood flow (r=0.72). CONCLUSIONS: Measurement of the TOI of the liver might be a non-invasive way to measure the distal ileal blood flow.

Animals↗

PubMed2004

Intravenous paracetamol (propacetamol) pharmacokinetics in term and preterm neonates.

BACKGROUND: The aim of this study was to describe propacetamol pharmacokinetics in term and preterm neonates to suggest dosing regimens. METHODS. A population pharmacokinetic analysis of paracetamol (acetaminophen) time-concentration profiles in 48 neonates was undertaken using non-linear mixed-effects models. Neonates were given either single (n=30) or multiple doses (n=18) of propacetamol infusion over 15 min. Neonates had a median postnatal age of 1 day (range, 1-76 days). Median post-conceptual age (PCA) was 35 weeks (range, 27-42 weeks), and median weight was 2.4 kg (range, 0.51-4 kg). RESULTS: The population volume of distribution estimate and between-subject variability (%) for a one-compartment model with zero-order input and first-order elimination was 70.4 l (30.7%)/70 kg. Clearance increased from 2.85 l/70 kg, CV 40.7% at 27 weeks PCA to reach 7.05 l/h per 70 kg by 42 weeks PCA (standardised to a 70-kg person using allometric "1/4-power" models). Between-occasion variability for volume of distribution and clearance were 17.4% and 26%, respectively. CONCLUSIONS: A mean paracetamol steady-state target concentration above 10 mg/l at trough can be achieved using a loading dose of 40 mg/kg and maintenance doses of 20 mg/kg 6 h in 28-week PCA neonates, 25 mg/kg 6 h at 32 weeks, 30 mg/kg 6 h at 36 weeks and 20 mg/kg 4 h at term (propacetamol doses). Since the role of the oxidative enzyme CYP2E1 and production of the hepatotoxic metabolite N-acetyl-p-benzoquinone-imine still is unknown in premature neonates, lower doses scaled by age-related clearance and centred on a daily dose of 60 mg/kg per day in a child of 6-8 years with a clearance of 0.25 l/h per kg (12.5 l/h per 70 kg) may be more appropriate.

Acetaminophen↗

PubMed2004

Association of patent ductus arteriosus and severe hypothyroidism in term newborns: coincidence or causal?

We report on 3 term newborns with the association of patent ductus arteriosus (PDA) and severe hypothyroidism attributed to thyroid agenesis (n = 2) or feto-maternal pit-1 deficiency (n = 1). This association suggests that sufficient thyroid hormone availability is among the prerequisites for normal postnatal ductal closure. Unravelling the maturational effects of thyroid hormone on the ductus arteriosus might also be relevant in preterm infants as further studies of the perinatal thyroid axis may clarify the potential role of thyroid hormone in PDA closure in preterm infants. Based on our observation, hypothyroidism should be considered in term infants with PDA.

Ductus Arteriosus, Patent↗

PubMed2004

The EPIBEL study: outcomes to discharge from hospital for extremely preterm infants in Belgium.

OBJECTIVE: To determine mortality and morbidity at discharge from the hospital of a large population-based cohort of infants who were born at <or=26 weeks' gestation. METHODS: Perinatal data were collected on extremely preterm infants who were alive at the onset of labor and born between January 1, 1999, and December 31, 2000, in all 19 Belgian perinatal centers. RESULTS: A total of 525 infants were recorded. Life-supporting care was provided to 322 liveborn infants, 303 of whom were admitted for intensive care. The overall survival rate of liveborn infants was 54%. Of the infants who were alive at the age of 7 days, 82% survived to discharge. Vaginal delivery, shorter gestation, air leak, longer ventilator dependence, and higher initial oxygen need all were independently associated with death; gender, plurality, and surfactant therapy were not. Among the 175 survivors, 63% had 1 or more of the 3 major adverse outcome variables at the time of discharge (serious neuromorbidity, chronic lung disease at 36 weeks' postmenstrual age, or treated retinopathy of prematurity). The chance of survival free from serious neonatal morbidity at the time of hospital discharge was <15% (21 of 158) for the admitted infants with a gestation <26 weeks. CONCLUSIONS: If for the time being prolongation of pregnancy is unsuccessful, then outcome perspectives should be discussed and treatment options including nonintervention explicitly be made available to parents of infants of <26 weeks' gestation within the limits of medical feasibility and appropriateness.

Belgium↗

PubMed2003

Pseudo-Bartter syndrome in a neonate on prostaglandin infusion.

UNLABELLED: We describe a case of iatrogenic pseudo-Bartter syndrome caused by administration of prostaglandin E1 (PGE1 alprostadil). Although the use of i.v. PGE1 is a well-established pharmacological therapy in neonates with a ductus-dependent congenital cardiopathy to ensure ductus-dependent flow, we could only find one other report on pseudo-Bartter syndrome related to PGE1 infusion. CONCLUSION: Primary Bartter syndrome is associated with endogenous increased levels of prostaglandins. Therefore, we postulate that the dose of prostaglandin E1 administered, immaturity and the genetic background are all relevant factors involved in the phenotypic presentation of iatrogenic pseudo-Bartter syndrome in this preterm infant.

Abnormalities, Multiple↗

PubMed2003

Systematic evaluation of pain in neonates: effect on the number of intravenous analgesics prescribed.

OBJECTIVE: To document the effect of systematic evaluation of pain in neonates on prescription of intravenous analgesics in a level-III neonatal intensive care unit (NICU) as a marker of increased awareness of treating and preventing pain. METHODS: Retrospective analysis of the number of yearly prescribed vials of intravenous analgesics in a level-III NICU during a period before (1996-1999) and after (2000 to August 2002) introduction of a multidimensional pain scale. Correction was carried out by multiple regression analysis for clinical co-variables (admissions, days on parenteral nutrition, days on respiratory support, surgical procedures), which also might explain changes in prescription of analgesics. Postoperative length (hours) of administration of analgesics was calculated in a group of infants (1996-2001) who all received cryotherapy for threshold retinopathy of prematurity (ROP) before (1996-1999) and since (2000-2001) introduction of pain evaluation. RESULTS: The number of yearly prescribed vials increased from 3140+/-619 (mean+/-SD) to 5915+/-675 ( P<0.005). There is also a significant increase in the number of surgical interventions ( P<0.05) but not in days on respiratory support, days on parenteral nutrition or in number of admissions. After correction for the number of surgical procedures, the increase in prescribed vials remained significant ( P<0.05). In infants who received cryotherapy, a significant increase in length of postoperative analgesia (65-107 h, P<0.01) was documented. Even after correction for the increased postoperative length of ventilation, duration of postoperative analgesia remained significantly ( P<0.05) longer. CONCLUSIONS: Systematic evaluation of pain increased awareness of treating and preventing pain in neonates, even after correction for clinical co-variables. This increase was not associated with an increase in potential side-effects (length of respiratory support, length of parenteral nutrition).

Acetaminophen↗

PubMed2003

Surgical therapy and histological abnormalities in functional isolated small bowel obstruction and idiopathic gastrointestinal perforation in the very low birth weight infant.

We examined surgical treatment, outcome, and histological findings in very low birth weight (VLBW) infants with functional isolated small bowel obstruction (FISBO) and idiopathic gastrointestinal perforation (IGIP). The files of 18 neonates (average gestational age 27.5 weeks; average birth weight 880 g), surgically treated for IGIP ( n = 12) or FISBO ( n = 6), were retrospectively reviewed. In both groups segmental or diffuse dilatation of the small bowel was seen. All but two perforations were localized in the small bowel. In half of the patients a discontinuous absence of the internal layer of the muscularis propria or muscularis mucosae was found. Signs of necrotizing enterocolitis (NEC) were absent. Most of the patients were treated with an enterostomy (IGIP: n = 11; FISBO: n = 4). Overall survival in both groups was 83%. Follow-up after enterostomy closure (mean 23 months) shows normal gastrointestinal function without failure to thrive in 67% of the survivors. Muscular wall abnormalities and small bowel distension are found in both FISBO and IGIP. Although the underlying etiology remains unclear, segmental muscular wall absence may be a major predisposing factor in both conditions. Creation of a temporary enterostomy is a valid surgical option in VLBW infants with minimal risk for recurrent obstruction and/or perforation. Survival and long-term gastrointestinal function is excellent. IGIP should be distinguished from NEC.

Enterostomy↗