Biomedical subjects

M Pohjavuori

Publications and source records attributed to M Pohjavuori.

At least 19 recordsLinked to original sources

PubMed2002

Early dexamethasone decreases expression of activation markers on neutrophils and monocytes in preterm infants.

AIM: To investigate the effects of early dexamethasone administration on activation of circulating neutrophils and monocytes in preterm infants with respiratory distress syndrome requiring treatment with surfactant. METHODS: Neonates (n = 30) with respiratory distress were randomized to receive dexamethasone (DEX group, 29.1 +/- 1.2 wk, 1223 +/- 156 g, n = 15) from the first postnatal day, or to serve as controls (control group, 29.2 +/- 1.4 wk, 1250 +/- 148 g, n = 15). Dexamethasone was given as a 4 d course (0.5 mg kg(-1) on postnatal days 1 and 2, and 0.25 mg kg(-1) on days 3 and 4). Polymorphonuclear leucocyte (PMN) and monocyte surface expression of CD11b, L-selectin and CD14 was quantified with flow cytometry, and plasma macrophage-inflammatory protein-1alpha (MIP-1alpha) with an enzyme-linked immunosorbent assay. Blood samples were collected on days 1, 2-3 and 5-7. RESULTS: In the DEX group 1/15, and in the control group 7/15 developed bronchopulmonary dysplasia (p < 0.04). PMN CD11b (median 100, range 70-190 vs 154, 96-213, p=0.01), monocyte CD14 (235, 102-433 vs 355, 219-533, p=0.01) and plasma MIP-1alpha (20 ng l(-1), 20-32 vs 37 ng l(-1), 20-70, p = 0.005) were lower in the DEX group at days 2-3. All adhesion molecule expression and plasma MIP-1alpha levels were comparable at days 5-7, with the exception of monocyte L-selectin expression levels, which remained lower in the DEX group. CONCLUSION: In preterm infants with respiratory distress syndrome, early dexamethasone causes downregulation of PMN and monocyte activation. This may attenuate pulmonary inflammation and improve pulmonary outcome.

Anti-Inflammatory Agents↗

PubMed2001

Prematurity at birth reduces the long-term risk of atopy.

BACKGROUND: Antigen exposure in early life has long-lasting effects on atopic sensitization. Thus the predisposition to atopy of children born preterm can be assumed to differ from that of children born at term. OBJECTIVE: The aim of this study was to evaluate the association between premature birth and atopy. METHODS: At an outpatient clinic, we examined 2 groups of 10-year-old children, 72 who were born preterm (birth weight < 1500 g) and 65 who were born at term (birth weight > 2500 g). The atopy data were collected with a questionnaire, by performing skin prick testing, and by measuring the serum total IgE level, 3 allergen-specific IgE levels, the eosinophil cationic protein level, and the blood eosinophil level. The data on perinatal and neonatal events affecting the preterm children were collected from the hospital records. RESULTS: By the age of 10 years, the children born preterm had significantly less atopy than the children born at term: 15% versus 31% of children in the 2 groups were defined as having had obvious atopy (P = .03, odds ratio 0.41, 95% CI 0.18-0.93). The mean value of total IgE level was significantly higher in the term group, 74 kU/L versus 41 kU/L (P = .02). By skin prick testing, the children born at term had positive reactions 2 to 3 times more often; 37% versus 17% of children in the groups had at least 1 positive reaction (P = .007). CONCLUSION: Our data show that prematurity at birth is linked with a decreased long-term risk of atopic sensitization.

Female↗

PubMed2001

Plasma cyclic guanosine monophosphate reflecting the severity of persistent pulmonary hypertension of the newborn.

The aim of the study was to examine the relationship between the plasma concentration of cyclic guanosine monophosphate (cGMP) and pulmonary pressure and hypoxia defined by oxygenation index (OI) in newborn infants with severe persistent pulmonary hypertension (PPHN) on inhaled nitric oxide (NO). In this prospective study, 18 newborn infants having Doppler ultrasound-diagnosed PPHN and treated with NO were investigated. The ratio of pulmonary artery to systemic artery pressure (PAP/SAP) and OI was assessed before treatment and at 0.5, 1, 12, and 24 h from the beginning of NO. At these time points, plasma concentrations of cGMP could be determined in 11 patients. The association of birth asphyxia as assessed by Apgar 1 min and 5 min and plasma cGMP before the NO treatment was examined. The initial median plasma concentration of cGMP was 37.3 pmol/ml (IQR 13.3-79.6). After the start of NO, cGMP increased significantly within 60 min (p = 0.003) and peaked at 12 h. Initial plasma cGMP was associated with Apgar score (1 and 5 min). OI decreased within 30 min of NO and PAP/SAP within 60 min. Persistent high PAP/SAP after 1 h of NO was associated with low cGMP concentration (r = 0.70, p = 0.02). We conclude that a significant increase in plasma cGMP is already evident after 60 min of NO therapy. This effect is accompanied by changes in oxygenation index and in pulmonary artery pressure. Initial plasma concentrations of cGMP were associated with hypoxia assessed as Apgar score.

Apgar Score↗

PubMed2001

Markers of type I and III collagen turnover as indicators of growth velocity in very low birth weight infants.

Monitoring postnatal growth in very low birth weight (VLBW) infants is complicated by the difficulty of obtaining reliable measurements. A need thus exists for safe and reliable indicators of such infants' short-term growth velocity. We set out to study whether markers of type I collagen synthesis [amino-terminal propeptide of type I procollagen (PINP)] or degradation [via the matrix metalloproteinase pathway, carboxyl-terminal telopeptide of type I collagen (ICTP)] or of type III collagen synthesis [amino-terminal propeptide of type III procollagen (PIIINP)] could serve as such indicators. PINP, ICTP, and PIIINP were measured for 48 VLBW infants (mean birth weight, 923 g; range, 540-1485 g; mean gestational age, 27.6 wk; range, 23.7-32.7 wk) at the age of 1, 2, 4, and 8 wk. At each time point, these were compared with concurrent growth velocity rigorously assessed by frequent lower leg (knemometry) and weight measurements. PINP showed a significant positive correlation with lower leg growth velocity at 1, 2, and 4 wk and with weight growth velocity at 2, 4, and 8 wk. PIIINP showed a significant positive correlation with lower leg growth at 1, 2, and 8 wk and with weight growth at 2 and 8 wk. The ICTP/PINP ratio, reflecting type I collagen degradation in relation to its synthesis, showed close negative correlations with lower leg growth at 1 wk (r = -0.46; P = 0.003), 2 wk (r = -0.51; P = 0.002), and 4 wk (r = -0.56; P = 0.001) and with weight growth at 2 wk (r = -0.39; P = 0.018), 4 wk (r = -0.59; P = 0.0003), and 8 wk (r = -0.53; P = 0.005). A high ICTP/PINP ratio was an accurate predictor of impaired growth; a high ICTP/PINP ratio was a more rapid and at least as sensitive and specific indicator of slow growth as weight gain. We conclude that PINP, PIIINP, and the ICTP/PINP ratio all reflect postnatal growth velocity in VLBW infants. The most robust of these indicators is the ICTP/PINP ratio, which may thus serve as a clinical tool in assessing short-term growth of these infants.

Biomarkers↗

PubMed2000

Phagocyte activation in preterm infants following premature rupture of the membranes or chorioamnionitis.

Phagocyte activation was studied in 48 preterm infants, gestational age 27.3 +/- 0.3 wk, birthweight 968 +/- 40 g, during the first postnatal week. Human neutrophil lipocalin as a marker of neutrophil activation was measured in plasma and tracheal aspirate fractions; and lysozyme, as a marker of monocyte and macrophage activation, in plasma. The concentration of plasma human neutrophil lipocalin was 69 (46-126) microg/l (median and quartiles), tracheal aspirate fraction fluid 213 (71-433) microg/l and plasma lysozyme 1337 (923-1764) microg/l. Infants born to mothers with premature rupture of the membranes or clinical chorioamnionitis (group A, n = 20) had significantly higher plasma [73 (58-151) vs 53 (38-108) microg/l; p=0.027], and tracheal aspirate fraction human neutrophil lipocalin [319 (129-540) vs 190 (57-324) microg/l; p = 0.019], and plasma lysozyme [1739 (1356-2021) vs 1140 (739-1557)microg/l; p=0.0001] than did infants whose mothers had intact membranes and who had no suspicion of infection (Group B, n = 28). In infants born to mothers receiving corticosteroids ante partum, correlations existed between time from treatment to delivery and plasma (r =0.322, p = 0.0256) and tracheal aspirate fraction human neutrophil lipocalin (r = 0.314, p = 0.0096).

Acute-Phase Proteins↗

PubMed1999

Intraindividual variability of infant whole-body plethysmographic measurements: effects of age and disease.

The intraindividual variability of whole-body plethysmographic measurements was studied in a large series of consecutive infants (N = 144), divided into two groups: a group of infants born very prematurely (PM, N = 63), with (N = 28) or without (N = 35) a history of bronchopulmonary dysplasia (BPD), and a group of infants with persistent respiratory symptoms (PRS, N = 81), i.e., wheezing (N = 53) or cough (N = 28). The intraindividual variability was determined within each test and between tests, separated by a 10-min interval. In both study groups, the between-test variability was significantly larger than that within tests. Expressed as the median coefficient of variation (CV), the between-test repeatabilities in the PRS group were 8.0% for thoracic gas volume (TGV), 17.5% for airway resistance (Raw), and 18.4% for specific airway conductance (sGaw), and in the PM group, 8.9% for TGV, 20.4% for Raw, and 20.7% for sGaw. However, the individual range of CVs was large, ranging from 3 to 19% for TGV and from 5 to 55% for sGaw. With respect to TGV, the difference between the groups was statistically significant (P = 0.03). In infants with a history of BPD, there was also a significant negative age dependency in CVs of sGaw (r = -0.50, P = 0. 009), showing larger variation among younger individuals. The presenting symptom (wheezing or cough) in the PRS group did not influence the measurement variability significantly, and neither did the degree of bronchial obstruction. We conclude that on a group basis, the repeatability of infant body plethysmographic measurements may be satisfactory for scientific studies demonstrating pharmacodynamic effects; however, the intraindividual measurement variability should be reported for each test conditions and for infant groups in each study. Due to the large range in individual variation and the influence of age and disease processes on the variation, for an individual child there is only questionable benefit from a given measurement, unless the intrasubject, between-test variability is assessed individually before interventions, such as a bronchodilation test.

Bronchopulmonary Dysplasia↗

PubMed1999

Mononuclear cell subpopulations in preterm and full-term neonates: independent effects of gestational age, neonatal infection, maternal pre-eclampsia, maternal betamethason therapy, and mode of delivery.

Blood samples from 29 preterm (24-32 weeks of gestation) and 21 full-term (37-42 weeks of gestation) neonates were analysed for surface markers of lymphocyte subtypes and macrophages, and the effects of gestational age, neonatal infection, maternal pre-eclampsia, maternal betamethason therapy and mode of delivery were assessed with multiple regression analysis. Gestational age alone had few independent effects (increase in CD3+, CD8+CD45RA+, and CD11alpha+ cells, and decrease in CD14+, HLA-DR- cells) during the third trimester on the proportions of the immune cell subtypes studied. Neonatal infection and mother's pre-eclampsia had the broadest and very opposite kinds of effects on the profile of immune cells in the blood. Infection of the neonate increased the proportions of several 'immature' cells (CD11alpha-CD20+, CD40+CD19-, and CD14+HLA-DR-), whereas mother's pre-eclampsia decreased the proportions of naive cell types (CD4+CD8+, CD5+CD19+). In addition, neonatal infection increased the proportion of T cells (CD3+, CD3+CD25+, and CD4+/CD8+ ratio, and CD45RA+ cells), while maternal pre-eclampsia had a decreasing effect on the proportion of CD4+ cells, CD4+/CD8+ ratio, and proportions of CD11alpha+, CD14+ and CD14+HLA-DR+ cells. Maternal betamethason therapy increased the proportion of T cells (CD3+) and macrophages (CD14+, CD14+HLA-DR+), but decreased the proportion of natural killer (NK) cells. Caesarean section was associated with a decrease in the proportion of CD14+ cells. We conclude that the 'normal range' of proportions of different mononuclear cells is wide during the last trimester; further, the effect of gestational age on these proportions is more limited than the effects of other neonatal and even maternal factors.

Antigens, CD↗

PubMed1998

Maturation of mismatch negativity in infants.

The mismatch negativity (MMN) is a pre-attentive change-specific component of the event-related brain potentials (ERPs). During the last decade this response has been intensively studied in adults, but investigations in children and especially in infants are still rare. Recent studies, however, have shown that MMN is also elicited in infants in response to changes in pure tones as well as in phonemes. The present study compared MMN in pre-term infants (conceptional age at the time of recording, 30-35 weeks), full-term newborns and full-term 3-month-old infants. Stimuli were Klatt-synthesized Finnish vowels /y/ and /i/. Previous studies have reported larger MMN amplitudes in school-age children compared with those obtained in adults. According to the results, however, the infant MMN amplitude seems to resemble that of adults. No significant differences in MMN amplitudes were found between the three age groups either. The mean MMN latency, however, decreased significantly with age, although in 3-month-old infants it was not much longer than in a previous study conducted in adults with the same stimuli.

Acoustic Stimulation↗

PubMed1998

Birth stress increases adrenomedullin in the newborn.

Adrenomedullin is a peptide that induces pulmonary vasodilation in experimental animals. Adrenomedullin was measured in blood samples from cord artery and vein from 41 term newborns. In 23 of the newborns delivered vaginally, levels of adrenomedullin in the cord artery, 71.8+/-45.8 pg ml(-1) (mean +/- SD), and vein, 75.6+/-45.2 pg ml(-1), were significantly higher than in 18 newborns delivered by elective Caesarean section (40.7+/-14.6 pg ml(-1) and 32.4+/-10.3 pg ml(-1), respectively; both p < 0.01). A significant correlation existed between the concentration of adrenomedullin and pH in the cord artery (r = -0.545, p = 0.002). The fetus responds to birth stress by secreting high concentrations of adrenomedullin. As a potent vasodilator, the peptide may play a role in postnatal cardiovascular adaptation.

Adrenomedullin↗

PubMed1996

The ontogenetically earliest discriminative response of the human brain.

Speech sounds elicited electric brain responses in healthy premature infants born 30-35 weeks after conception, demonstrating that the human brain is able to discriminate speech sounds even at this early age, well before term, and supporting previous results suggesting that the human fetus may learn to discriminate sounds while still in the womb. We presented preterm infants with stimulus sequences consisting of a repetitive vowel that was occasionally replaced by a different vowel. This infrequent vowel elicited a response resembling the adult mismatch negativity, which is known to reflect the brain's automatic detection of stimulus change. The present results constitute the ontogenetically earliest discriminative response of the human brain ever recorded.

Brain↗

PubMed1996

Pulmonary artery pressure in term and preterm neonates.

Systolic pulmonary artery pressure (PAP) during the first 4 days after birth was determined in 41 healthy term and 46 preterm infants by measuring ductal Doppler flow velocity and systemic arterial pressure (SAP). Among preterm infants, 21 had respiratory distress syndrome (RDS) and 25 did not. Sequential indices within 96 h of age were presented respectively. At the ages of 2 and 12 h the ratio between pulmonary and systemic arterial pressure was significantly higher in term than in preterm infants without RDS (p < 0.05). At the age of 24 h, PAP to SAP ratio was similar in all study groups. Between 48 and 72 h, PAP to SAP ratio was significantly higher in preterm infants with RDS than in infants without RDS (p < 0.05). Our findings indicated that: (1) in healthy fullterm infants pulmonary artery pressure fell to subsystemic level during the first 12 h, indicating the critical time in circulatory transition; (2) prematurity did not affect ductal closure times significantly; and (3) RDS was associated with prolonged ductal patency and delayed postnatal circulatory adaptation characterized by pulmonary hypertension.

Blood Flow Velocity↗

PubMed1995

Total parenteral nutrition-associated cholestasis in surgical neonates may be reversed by intravenous cholecystokinin: a preliminary report.

Neonatal infants who require total parenteral nutrition (TPN) after major operations are susceptible to total parenteral nutrition-associated cholestasis (TPNAC). A therapeutic dilemma ensues if cholestasis does not resolve after the institution of full enteral nutrition. The authors report the reversal of TPN-associated cholestasis by intravenous cholecystokinin in eight infants who had undergone major surgery during the neonatal period. The indications for surgery were necrotizing enterocolitis in three patients, midgut volvulus in one, gastroschisis in one, diaphragmatic hernia in one, necrosis of the stomach in one, and cardiac anomaly in one. Four of the infants were premature. Median duration of TPN was 25 days (range, 20 to 150 days). Seven patients were weaned from TPN before treatment with cholecystokinin was instituted Mean duration of pretreatment full enteral nutrition in these seven patients was 35 days (range, 20 to 55 days). One girl with short gut syndrome tolerated only 10% of her caloric needs via the enteral route. All patients had alcoholic stools, conjugated hyperbilirubinemia, no excretion of Technetium-labeled HIDA to the biliary tree or duodenum (six patients), and significantly elevated liver enzyme values. In three patients, echography showed biliary sludge or stones in the gall bladder. Porcine cholecystokinin (2 IDU/kg) was administered intravenously for 3 to 5 days. If the stool color did not normalize, cholecystokinin injections were repeated using a larger dose (4 IDU/kg). In seven patients, including the girl with short gut syndrome, the clinical jaundice and conjugated hyperbilirubinemia completely resolved within 1 to six weeks. No biliary sludge or stones were seen in the posttreatment echography in any of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholecystokinin↗

PubMed1995

Diagnosis of fatal infantile defects of the mitochondrial respiratory chain: age dependence and postmortem analysis of enzyme activities.

We studied two diagnostic aspects of fatal infantile defects of the mitochondrial respiratory chain: the age dependence of muscle mitochondrial enzyme activities and the reliability of diagnosis from autopsy samples. In morphologically normal quadriceps muscle samples of 46 children between the ages of 3 days and 15 years, activities of complex I plus III (NADH:cytochrome c oxidoreductase) and complex II plus III (succinate:cytochrome c oxidoreductase) increased 2-fold during the first three years of life, while that of complex II (succinate dehydrogenase), complex IV (cytochrome c oxidase), and citrate synthase did not show significant correlation with age. We suggest that these changes are related to age and stress the importance of strictly age-matched controls when diagnosing a mitochondrial disease of early childhood. The value of autopsy samples in diagnostic studies was evaluated by comparing mitochondrial enzyme activities in quadriceps muscle from autopsies and from surgical biopsies. In quadriceps muscle mitochondria, all the enzyme activities studied remained stable for at least 3 h after death. Using age-matched controls and autopsy samples, we diagnosed a respiratory chain enzyme deficiency in two infants, and the defects were confirmed in cultured skin fibroblasts.

Adolescent↗

PubMed1995

Neonatal Candida parapsilosis outbreak with a high case fatality rate.

A Candida parapsilosis outbreak of 58 cases in a neonatal intensive care unit lasted for 55 months. Patients infected by or colonized with C. parapsilosis were mainly very low birth weight infants (birth weight < 1500 g). Their mean birth weight was 817 g and their mean gestational age was 28 weeks. Statistical analysis including logistic regression confirmed that prematurity was the main risk factor. The analysis also suggested that C. parapsilosis infection (or colonization) was associated with a poor prognosis. In infants with gestational age < 29 weeks the risk for death in C. parapsilosis-infected patients was 16-fold greater than in those with no C. parapsilosis infection. The case fatality rate of C. parapsilosis patients was higher than that of the controls (9 of 23 vs. 1 of 40; P < 0.0001). The outbreak was most likely a result of cross-infection because C. parapsilosis could be isolated only from the patients and from the hands of four nurses immediately after they had cared for a colonized patient. Cessation of the outbreak was temporally associated with long term parenteral fluconazole (6 mg/kg/day) prophylaxis.

Antifungal Agents↗

PubMed1994

CRIB and SNAP: assessing the risk of death for preterm neonates.

The performance of three scoring systems for assessing mortality risk for neonates--clinical risk index for babies (CRIB), score for neonatal acute physiology (SNAP), and SNAP's perinatal extension (SNAP-PE)--were tested in the same set of patients. In 222 neonates weighing less than 1500 g at birth, CRIB scores were significantly better for assessing mortality risk than SNAP (p = 0.017) or SNAP-PE (p < 0.001), areas under receiver operating characteristic curves being 0.89 (SE 0.02), 0.82 (0.03), and 0.79 (0.03), respectively. Male sex was independently associated with poor prognosis after taking the CRIB score into account with a risk ratio of 2.75. We conclude that CRIB is the most useful score for comparing the performance of neonatal intensive-care units. New treatment methods, however, may require modifications to the system.

Female↗

PubMed1993

Surgical treatment of intractable cholestasis associated with total parenteral nutrition in premature infants.

We report surgical reversal of intractable total parenteral nutrition (TPN)-associated cholestasis refractory to conservative treatment in 9 premature infants. Indications for TPN were poorly tolerated enteral feedings in all patients. Five patients had undergone gastrointestinal operations; in addition, 7 of the 9 patients had had bacterial sepsis. The median duration of TPN was 28 days (range, 20 to 50 days). The median duration of preoperative full enteral nutrition after weaning from TPN was 34 days (range, 16 to 95 days). All patients had progressive conjugated hyperbilirubinemia, no excretion of Tc-labeled HIDA to the biliary tree and duodenum, and markedly elevated liver enzyme values. Intraoperative cholangiography showed normal biliary anatomy in all cases; in addition, 2 patients had gallbladder stones. Bile was hyperviscous in all patients and contained biliary sludge in 4. The biliary tree was irrigated and the liver biopsied in all patients. The gallbladder was removed from 2 patients who had stones in the gallbladder. Liver histology was consistent with TPN-associated cholestasis in all cases, and in addition, 4 cases showed significant destruction of intrahepatic bile ducts. One patient died 2 weeks postoperatively from intracerebral hemorrhage. Jaundice completely resolved in other patients within 2 weeks. HIDA-biligraphy performed 1 to 2 months postoperatively showed normal excretion of the radioactive marker to the biliary tree and duodenum in all cases. The functional abnormality in bile excretion and bile duct motility in TPN-associated cholestasis may be reversed by irrigation of the biliary tree. Surgical intervention should be considered when cholestasis is progressive and refractory to medical management.

Cholestasis↗

PubMed1993

Outcome at twelve months of adjusted age in very low birth weight infants with lung immaturity: a randomized, placebo-controlled trial of human surfactant.

We compared the neurodevelopmental outcome of extremely premature, surfactant-deficient infants who received either prophylactic surfactant at birth, "rescue" surfactant after the clinical diagnosis of respiratory distress syndrome was established, or placebo. Infants studied were participants in a randomized, bicenter (San Diego, Calif., and Helsinki, Finland), controlled trial of human surfactant therapy. One hundred fifty infants (prophylaxis group, 63 infants; rescue group, 57; placebo group, 30) were prospectively enrolled at 38 weeks of gestational age. There were no neonatal intergroup differences in the incidence or severity of sonographic central nervous system abnormality or retinopathy. One hundred forty-five infants were alive at 1 year of adjusted age, at which time growth, neurosensory, and neurologic outcome were similar in all three treatment groups at both centers. Cerebral palsy occurred in 20% overall. Five infants (3.5%) were functionally blind. However, infants treated at birth had lower mean mental and motor scores on the Bayley Scales of Infant Development compared with those of infants rescued with surfactant after the onset of respiratory distress syndrome (Mental Development Index: 78 vs 96, p = 0.02; Psychomotor Development Index: 73 vs 87, p = 0.04). Chronic lung disease occurred more frequently in the prophylactically treated group and contributed to the subjects' neurologic and developmental morbidity. Because prophylactic surfactant treatment offered no neurodevelopmental advantage and may contribute to poorer outcome, we currently recommend early surfactant replacement only for those infants who have postnatal evidence of respiratory distress syndrome.

Brain↗

PubMed1993

Pharmacokinetics of fluconazole in very low birth weight infants during the first two weeks of life.

OBJECTIVE: To find a dose of fluconazole for very low birth weight infants during an outbreak of Candida parapsilosis. METHODS: Twelve premature infants (mean gestational age, 27.4 weeks; mean birth weight, 912 gm) receiving fluconazole prophylactically from the first day of life were enrolled in an open phase I-II pharmacokinetics, safety, and tolerance trial. Up to 5 doses of 6 mg/kg were administered intravenously every 72 hours during the first 2 weeks of life. Pharmacokinetic characteristics of fluconazole were determined after the first, third, and fifth doses. RESULTS: The mean peak and trough concentrations after the 3 doses were 5.5 and 2.6 micrograms/ml, 12.8 and 4.3 micrograms/ml, and 10.0 and 2.9 micrograms/ml (p = 0.0002 and p = 0.07), respectively. The mean fluconazole half-lives were 88.6 hours (n = 7), 67.5 hours (n = 9), and 55.2 hours (n = 4; p = 0.3). The mean total clearance corrected for weight (CL/kg) was 0.18 ml/min/kg (n = 7), 0.33 ml/min/kg (n = 7), and 0.52 ml/min/kg (n = 4; p = 0.02), and the mean volume of distribution 1.18 L/kg (n = 7), 1.84 L/kg (n = 7), and 2.25 L/kg (n = 4; p = 0.05). Weight-corrected clearance increased with postnatal age (r = 0.61; p = 0.007). CONCLUSIONS: With the used fluconazole dose (6 mg/kg every 3 days), the mean serum peak and trough concentrations increased during the first week but decreased during the second week. After the first week we suggest a dose of 6 mg/kg every 2 days, or even daily.

Candidiasis↗