Behaviour of 4- to 5-year-old nondisabled ELBW children: Outcomes following group-based physiotherapy intervention.

BACKGROUND: Extreme prematurity or extremely low birth weight (ELBW) can adversely affect behaviour. Nondisabled ELBW children are at risk of behavioural problems, which may become a particular concern after commencement of formal education. This study explored the frequency of behavioural and emotional problems amongst nondisabled ELBW children at 4 to 5 years of age and whether intervention had a positive influence on behaviour. The relationship between behaviour, gender, and other areas of performance at 5 years was explored. METHODS: Fifty 4-year-old children (born <28 weeks gestation or birth weight <1,000 g) with minimal/mild motor impairment were randomly allocated to intervention (n = 24) or standard care (n = 26). Intervention was 6 group-based physiotherapy weekly sessions and home programme. Standard care was best practice advice. The Child Behavior Checklist (CBCL) for preschool children was completed at baseline and at 1-year post-baseline. Other measures at follow-up included Movement Assessment Battery for Children Second Edition, Beery Visual-Motor Integration Test 5th Edition, and Peabody Picture Vocabulary Test 4th Edition. RESULTS: The whole cohort improved on CBCL total problems score between baseline (mean 50.0, SD 11.1) and 1-year follow-up (mean 45.2, SD 10.3), p = .004. There were no significant differences between groups over time on CBCL internalizing, externalizing, or total problems scores. The intervention group showed a mean difference in total problems score of -3.8 (CI [1.5, 9.1]) between times, with standard care group values being -4.4 (CI [1.6, 7.1]). Males had higher total problems scores than females (p = .026), although still performed within the "normal" range. CBCL scores did not correlate with other scores. CONCLUSIONS: The behaviour of nondisabled ELBW children was within the "normal" range at 4 to 5 years, and both intervention and standard care may have contributed to improved behavioural outcomes. Behaviour was not related to performance in other developmental domains.

Prediction of outcome following hypoxia/ischaemia in the human infant using cerebral impedance.

OBJECTIVE: Changes in cerebral impedance in the newborn piglet are able to discriminate, within 1-2 h of acute hypoxia, between animals which will have a good neurological outcome, and those who have suffered more severe hypoxia resulting in poor outcome. The aim of this study was to determine if cerebral impedance could be used to identify those human infants with an encephalopathy following acute hypoxia who subsequently have a poor neurological outcome. It is these infants who may benefit most from neural rescue treatment. METHODS: Twenty-four newborn term infants with evidence of severe acute intrapartum hypoxia and encephalopathy were studied. Bioimpedance spectroscopy was commenced as soon as possible after birth and repeated every 30 min until the infant was 12 h old. Neurodevelopmental outcome was assessed at 12 months of age. RESULTS: Although cerebral impedance was different to control values, there was no significant difference in cerebral impedance between hypoxic babies with normal and those with abnormal development. CONCLUSION: Cerebral impedance was increased in hypoxic babies, as predicted from animal data, but the method was not suitable for discrimination of outcome. SIGNIFICANCE: Cerebral impedance is not useful for early identification of infants who subsequently have a poor outcome after acute intrapartum hypoxia and who may benefit from neural rescue treatment.

Routine neonatal postextubation chest physiotherapy: a randomized controlled trial.

OBJECTIVE: To test the effects of a neonatal postextubation programme on the incidence of postextubation collapse and adverse outcomes. METHODS: A randomized controlled trial was carried out at the Mater Mothers' Hospital, Brisbane. Mechanically ventilated infants were randomized into one of two groups, physiotherapy group--which involved a regimen of chest wall percussion and oropharyngeal suctioning and control group - which involved suctioning without the percussion unless indicated. Chest X-rays were taken at 6 h and at 24 h postextubation. The primary outcome measure was postextubation collapse as determined by a paediatric radiologist blinded to the group allocation. RESULTS: One hundred and seventy-seven neonates were enrolled in the trial between 1997 and 1999. After an interim analysis, the trial was stopped early. No statistically significant difference was shown in the rate of postextubation collapse (15 of 87 (17.2%) physiotherapy group and 17 of 86 (19.8%) control group (P = 0.85)). No differences were shown between the groups in the number of apnoeic or bradycardic events, duration of requirement for supplemental oxygen or the need for re-intubation within 24 h postextubation. CONCLUSION: The results of this trial suggest that a routine neonatal postextubation chest physiotherapy programme for all infants is not indicated. There was no evidence that chest physiotherapy is associated with any adverse outcomes.

High dose caffeine citrate for extubation of preterm infants: a randomised controlled trial.

OBJECTIVE: To compare two dosing regimens for caffeine citrate in the periextubation period for neonates born at less than 30 weeks gestation in terms of successful extubation and adverse effects. DESIGN: A multicentre, randomised, double blind, clinical trial. SETTING: Four tertiary neonatal units within Australia. PATIENTS: Infants born less than 30 weeks gestation ventilated for more than 48 hours. INTERVENTIONS: Two dosing regimens of caffeine citrate (20 v 5 mg/kg/day) for periextubation management. Treatment started 24 hours before a planned extubation or within six hours of an unplanned extubation. MAIN OUTCOME MEASURE: Failure to extubate within 48 hours of caffeine loading or reintubation and ventilation or doxapram within seven days of caffeine loading. RESULTS: A total of 234 neonates were enrolled. A significant reduction in failure to extubate was shown for the 20 mg/kg/day dosing group (15.0% v 29.8%; relative risk 0.51; 95% confidence interval (CI) 0.31 to 0.85; number needed to treat 7 (95% CI 4 to 24)). A significant difference in duration of mechanical ventilation was shown for infants of less than 28 weeks gestation receiving the high dose of caffeine (mean (SD) days 14.4 (11.1) v 22.1 (17.1); p = 0.01). No difference in adverse effects was detected in terms of mortality, major neonatal morbidity, death, or severe disability or general quotient at 12 months. CONCLUSIONS: This trial shows short term benefits for a 20 mg/kg/day dosing regimen of caffeine citrate for neonates born at less than 30 weeks gestation in the periextubation period, without evidence of harm in the first year of life.

Cot-nursing using a heated, water-filled mattress and incubator care: a randomized clinical trial.

AIMS: To evaluate the thermal responses and weight gain in preterm infants nursed in a cot on a heated, water-filled mattress (HWM) compared with infants receiving care in an air-heated incubator and to compare mothers' stress, anxiety levels and perceptions of their infants in the two groups. METHODS: Stable preterm infants weighing 1300 to 1500 g were enrolled, being randomly allocated to either the study group (n = 41) receiving care in a cot on an HWM, or the control group (n = 33) receiving incubator care. The mean daily body temperature and episodes of cold stress and hyperthermia were recorded. Weight gain (g kg(-1) body weight d(-1)) was also calculated. The mothers completed questionnaires on their perceptions of their infants, and their anxiety and stress levels before randomization, and 2-3 wk later during the trial. RESULTS: The mean body temperature was similar for the first week of the trial (study group 36.9 degrees C vs controls 36.9 degrees C). There were no significant differences in the incidence of cold stress, while more hyperthermic episodes were seen in the study group (p = 0.03). There were no significant differences in weight gain during the first (study group 21.4 g vs controls 19.6 g) or second weeks of the trial (study group 20.5 g vs controls 19.2 g). Neonatal morbidity did not differ between the groups. There were no differences in mothers' perceptions of their babies, or feelings of stress or anxiety. CONCLUSION: There were no differences between infants cot-nursed on an HWM and those receiving incubator care, with the exception of episodes of high temperature. The results suggest that the HWM may be used safely for low-weight preterm infants.

Psychoeducational outcome at school age of preterm infants with bronchopulmonary dysplasia.

OBJECTIVE: To investigate the cognitive performance and educational attainment at school-age of children with bronchopulmonary dysplasia (BPD), compared with a preterm control group of children. METHODS: Seventy preterm infants with BPD and 61 birth weight matched controls were prospectively followed-up to school-age. The Weschler Intelligence Scale for Children - III (WISC), the Wide Range Achievement Test (WRAT) and the Developmental Test of Visual Motor Integration (VMI) were administered. The results were compared between the two groups and multiple regression analyses were performed to determine the effect of confounding variables. RESULTS: The children in the BPD group performed less well on the Full Scale IQ (mean 86.7 vs 93.5; 95% CI, 1.9-11.7), Verbal IQ (mean 87.1 vs 94.1; 95% CI, 2.0-12.0) and the Performance IQ (mean 88.6 vs 95.2; 95% CI, 2.0-11.2) of the WISC, the reading component of the WRAT (mean 93.8 vs 98.9; 95% CI, 0.3-9.8) and the VMI (mean 88.9 vs 93.3; 95%, CI 1.1-7.8). Despite controlling for social and biological variables, statistical differences persisted for Full Scale and Verbal IQ and reading. A Verbal IQ >1 SD below the mean was found in 41% of BPD children compared to 21% of controls, while on the reading component of the WRAT a greater proportion of BPD children also had scores>1 SD below the mean. CONCLUSION: Impaired psychoeducational performance was found in preterm children with BPD compared to controls, especially in the areas of language abilities and reading skills. This supports a greater need for special educational services and counseling for parents for these children.

Cot-nursing versus incubator care for preterm infants.

BACKGROUND: An optimal thermal environment is desirable for preterm infants. These infants are usually nursed in incubators, but cot-nursing may provide an alternative. Measures to assist the maintenance of body temperature for smaller infants in open cots include extra clothing/bedding, warming up the nursery and heating the cot mattress. Recently a heated water-filled mattress has been developed to maintain the temperature of a cot-nursed preterm infant. While there may be benefits of nursing preterm infants in open cots, there may be potential risks such as nosocomial infection caused by more handling due to easier access. OBJECTIVES: Among preterm infants allocated to cot-nursing vs incubator care in neonatal period, to assess effects on their temperature control and weight gain. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of electronic databases: Oxford Database of Perinatal Trials; Cochrane Controlled Trials Register (Cochrane Library Issue 4 2001); MEDLINE (1966-2001); and CINAHL (1982-2001), previous reviews including cross references. SELECTION CRITERIA: All trials using random or quasi-random patient allocation in which infants receiving care in standard newborn cots were compared to infants managed in a conventional air heated incubator. DATA COLLECTION AND ANALYSIS: The authors independently assessed trial quality and extracted data for the primary outcomes of temperature control and weight gain. Meta-analysis was conducted using a fixed effects model. Results are presented as relative risk (RR) for categorical data and mean difference (MD) and weighted mean differences (WMD) for data measured on a continuous scale. MAIN RESULTS: Nine potential studies were identified of which four, involving 173 babies, were included in this review. When compared to incubator care, cot-nursing resulted in a statistically significantly higher mean body temperature (MD 0.30 degrees C; 95% CI 0.10, 0.50, one trial) and a decrease in proportion of infants not breast feeding at hospital discharge (RR 0.52; 95% CI 0.28, 0.94, two trials, 77 infants). No statistically significant difference was shown in weight gain, reported by two trials involving 69 infants. The comparison of cot-nursing using a heated water-filled mattress versus incubator care, which included four trials and a total of 149 infants, produced similar results. Cot-nursing with warming of the nursery resulted in statistically significantly smaller weight gain during week one compared to the incubator group in one trial that involved 49 infants (MD -5.90 g/kg/day; 95% CI -11.13, -0.67) with no significant difference found for weeks two and three. REVIEWER'S CONCLUSIONS: Due to the small numbers of trials included and infants studied, and the resulting imprecision in the measures of effect for all outcomes, the review does not give a clear indication for the role of cot-nursing for preterm infants. Further assessment of the role of cot nursing for preterm infants using randomised controlled trials is necessary.

Chest physiotherapy for preventing morbidity in babies being extubated from mechanical ventilation.

BACKGROUND: Chest physiotherapy has been used to clear secretions and help lung ventilation in newborns who have needed mechanical ventilation for respiratory problems. However concerns about the safety of some forms of chest physiotherapy have been expressed. OBJECTIVES: To assess the effects of active chest physiotherapy on babies being extubated from mechanical ventilation for neonatal respiratory failure. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of electronic databases: Oxford Database of Perinatal Trials; Cochrane Controlled Trials Register (Cochrane Library Issue 4 2001); MEDLINE (1966-2001); and CINAHL (1982-2001), previous reviews including cross references, abstracts, conferences, symposia proceedings, expert informants and journal hand searching mainly in the English language. SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which active chest physiotherapy was compared with non-active techniques (eg positioning and suction alone) or no intervention in the periextubation period. DATA COLLECTION AND ANALYSIS: Assessment of methodological quality and extraction of data for each included trial was undertaken independently by the authors. Data were extracted for the primary outcomes of postextubation lobar collapse, use of reintubation, duration of oxygen therapy, intracranial haemorrhage, cerebral cystic lesions, long term neurosensory impairment and death. Subgroup analysis was performed on different treatment frequencies and gestational age less than 32 weeks. Meta-analysis was conducted using a fixed effects model. Results are presented as relative risk (RR), risk difference (RD) and number needed to treat (NNT) for categorical data and mean difference (MD) for data measured on a continuous scale. All outcomes are reported with the use of 95% confidence intervals. MAIN RESULTS: In this review of four trials, two of which were carried out 15 & 23 years ago, no clear benefit of periextubation active chest physiotherapy can be seen. Active chest physiotherapy did not significantly reduce the rate of postextubation lobar collapse [RR 0.80 (95% CI 0.49,1.29)], though a reduction in the use of reintubation was shown in the overall analysis: RR 0.32 (95% CI 0.13,0.82); RD -7% (95% CI-13, -2); NNT 14 (95% CI 8, 50). There is insufficient information to adequately assess important short and longer term outcomes, including adverse effects. REVIEWER'S CONCLUSIONS: The results of this review do not allow development of clear guidelines for clinical practice. Caution is required when interpreting the possible positive effects of chest physiotherapy of a reduction in the use of reintubation and the trend for decreased post-extubation atelectasis as the numbers of babies studied are small, the results are not consistent across trials, data on safety are insufficient, and applicability to current practice may be limited. Further randomised controlled trials addressing the role of prophylactic active chest physiotherapy for neonates in the postextubation period may be unwarranted.

Maternal antecedents for cerebral palsy in extremely preterm babies: a case-control study.

The study aimed to identify significant antenatal risk factors for cerebral palsy (CP) among extremely preterm infants with a matched case-control design. Infants born between 1989 and 1996 at 24 to 27 weeks' gestation who survived to hospital discharge were evaluated: 30 with a proven diagnosis of CP at 2 years corrected for prematurity and 120 control children matched for gestational age without CP. Information on maternal obstetric risk factors and medication was obtained. Matched analyses were performed and odds ratios (OR) and 95% confidence intervals (CI) were calculated. An antenatal diagnosis of intrauterine growth restriction was associated with an increased risk of CP (OR 6.6; 95% CI 1.8 to 25.2), while maternal administration of corticosteroids was associated with a reduced risk of CP (OR 0.4; 95% CI 0.1 to 0.98). A high rate of placental histopathology was achieved but no relation between clinical or histological chorioamnionitis or funisitis and CP was demonstrated. Maternal preeclampsia was not associated with a statistically significant reduction in the risk of CP. It is concluded that a reduced risk of CP in extremely preterm infants is associated with the antenatal use of corticosteroids.

Childhood neglect and cognitive development in extremely low birth weight infants: a prospective study.

OBJECTIVE: To examine the relationship between child maltreatment and cognitive development in extremely low birth weight infants, adjusting for perinatal and parental risk factors. METHODS: A total of 352 infants with birth weight of <1000 g were followed prospectively for 4 years. The data were analyzed with regard to perinatal and parental risk factors and referrals for suspected child maltreatment to government agencies. Perinatal risk factors included birth weight, gestation, gender, periventricular hemorrhage, ventricular dilation, home oxygen requirement, and necrotizing enterocolitis. Parental risk factors included maternal age, race, marital status, education, and hospital insurance status. Cognitive z scores were calculated at 1, 2, and 4 years, and head circumference z scores were calculated at birth, 2 years, and 4 years. RESULTS: Fifteen percent of infants were referred to child protective services for suspected child maltreatment. The adjusted general cognitive index at 4 years was significantly reduced in infants who were referred for neglect (-17.6; 95% confidence interval: -3.3, -31.9). Infants whose neglect was substantiated had a progressive decline in their cognitive function over time (cognitive z scores: -0.97, -1.37, and -2.05 standard deviations at 1, 2, and 4 years, respectively), compared with non-neglected infants (z scores: -0.04 to -0.36). They had a significantly smaller head circumference at 2 and 4 years but not at birth (adjusted z score at 4 years: -0.812; 95% confidence interval: -0.167, -1.458). Perinatal risk factors and physical disability were not related to maltreatment referral; only parental factors were independent predictors. CONCLUSIONS: Childhood neglect is associated significantly with delayed cognitive development and head growth. Addressing risk factors antenatally and in early childhood may improve outcomes.

Conductive hearing loss in preterm infants with bronchopulmonary dysplasia.

OBJECTIVE: To determine the risk of conductive hearing loss in preterm infants with bronchopulmonary dysplasia (BPD) and preterm controls. METHODOLOGY: The study population consisted of 78 infants with BPD of 26-33 weeks gestation and 78 controls of similar gestational age matched for broad-based birthweight categories. An auditory brainstem response (ABR) audiology was performed shortly before hospital discharge. Visual reinforcement orientation audiometry (VROA) and impedance audiometry were performed at 8-12 months corrected for prematurity. Infants with persistent audiological abnormalities were referred for evaluation to paediatric ENT surgeons. RESULTS: Infants with BPD had a significantly higher rate of ABR abnormalities (BPD: 22%, controls: 9%; P = 0.028). On VROA and impedance audiometry, the infants with BPD also had a higher rate of persistent abnormalities. Following ENT assessment, 22.1% of infants with BPD and 7.7% of controls had persistent conductive dysfunction requiring myringotomy and grommet tube insertion (P = 0.03). Most of these infants had normal ABR audiometry at hospital discharge. CONCLUSIONS: Preterm infants with BPD are at high risk of persistent conductive hearing loss late in the first year of life compared to controls. An ABR audiology conducted at the time of hospital discharge does not predict accurately later conductive hearing problems. Infants with BPD should have routine audiological evaluation toward the end of the first year of life.

Long term outcome of twin-twin transfusion syndrome.

AIMS: To compare the perinatal mortality and morbidity of infants with twin-twin transfusion syndrome (TTTS) with those of gestation matched twin controls and to assess the neurodevelopmental outcome of surviving twins with TTTS. METHODS: A cohort of 17 consecutive pregnancies with TTTS was enrolled over three years together with gestation matched twin pregnancies unaffected by TTTS. Serial amnioreduction for the TTTS pregnancies was performed as appropriate. Perinatal death and neonatal morbidities were recorded for both the TTTS cohort and controls. The TTTS survivors had neurodevelopmental follow up to at least 2 years of age. RESULTS: In 12 of the pregnancies, serial amniocenteses were performed, but, in five, the infants were born before intervention. The mean gestational age at delivery was 29.1 weeks (range 23-36). There were five intrauterine deaths in the TTTS cohort and six neonatal deaths (survival 68%). In the control group, there was one intrauterine death and five neonatal deaths (survival 82%). Infants in the TTTS group had a greater requirement for inotropes (p = 0.04) and a higher incidence of renal failure (p = 0.005). Periventricular leucomalacia and cerebral atrophy were seen in 17% of the TTTS group, but none of the controls (p = 0.03). The 23 surviving TTTS infants were all followed up, with 22% having significant neurological morbidity: cerebral palsy and global developmental delay. CONCLUSIONS: Twins with TTTS have high perinatal mortality and neonatal morbidity, and long term neurodevelopmental morbidity in survivors is high. Further investigation into the pathogenesis and management of TTTS is required.

Chest physiotherapy for preventing morbidity in babies being extubated from mechanical ventilation.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To assess the effects of active chest physiotherapy on babies being extubated from mechanical ventilation for neonatal respiratory failure. SEARCH STRATEGY: The standard search strategy for the Neonatal Review Group was used as outlined in the Cochrane Handbook in the Cochrane Library. SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which active chest physiotherapy was compared with non-active techniques (eg positioning and suction alone) or no intervention in the periextubation period. The methodological quality of each trial was assessed by two independent authors. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two authors. The data were analysed from 3 trials. Subgroup analysis was performed on different treatment frequencies. MAIN RESULTS: In this review of 3 small trials, 2 of which were carried out 10 & 20 years ago, no clear benefit of periextubation active chest physiotherapy can be seen. Active chest physiotherapy did not significantly reduce the rate of postextubation lobar collapse (RR 0.69;0.33,1.45), though a reduction in the use of reintubation was shown in the overall analysis (RR 0.24;0.08,0.75). Subgroup analysis of different treatment frequencies showed the same effect with more frequent treatment (1 & 2 hourly) but showed a trend to increased lobar collapse, and no reduction in the use of reintubation, with less frequent treatment (4 hourly). There is insufficient information to assess other important short and long term outcomes, including adverse effects. REVIEWER'S CONCLUSIONS: The results of this review do not allow development of clear guidelines for clinical practice. Caution is required when interpreting the possible positive effects of chest physiotherapy of a reduction in the use of reintubation and the trend for decreased post-extubation atelectasis as the numbers of babies studied are small, the results are not consistent across trials, data on safety are insufficient, and applicability to current practice may be limited.

The influence of growth on development outcome in extremely low birthweight infants at 2 years of age.

OBJECTIVE: To determine if weight < 3rd and < 10th centile at 2 years in extremely low birthweight (ELBW) infants is associated with problems of development and motor skills, and whether this association is explained by perinatal risk status. METHODOLOGY: One hundred and ninety-eight of 226 (88%) surviving ELBW infants born between January 1987 and December 1992 were assessed at 2 years corrected age. Children were classified as being at low perinatal risk (n = 128) or high perinatal risk (n = 70) for adverse developmental outcome based on perinatal risk factors. Weight at 2 years was classified as < 3rd, 3rd-9th or > or = 10th centile for age and gender. Development was assessed using the Griffiths Mental Developmental Scales and motor skills using the Neurosensory Motor Developmental Assessment (NSMDA). RESULTS: For the total study group weight centile was strongly related to General Quotient (GQ) and motor abilities. For children < 3rd percentile (n = 48) mean (GQ) was 90.4 (SD, 15.9), for children between the 3rd-9th percentile (n = 49) 91.5 (SD, 17.9), and for children > or = 10th percentile (n = 99) mean GQ was 99.8 (SD, 8.6). The association with mean GQ and NSMDA category occurred for the high-risk subgroup and became non-significant in the low-risk subgroup if neurologically abnormal children were excluded. Other perinatal risk factors, exposure to breast milk, level of maternal education, marital status and history of feeding problems or infections over the 2 years did not confound this association. CONCLUSION: Low weight percentile at 2 years was related to adverse developmental outcome in ELBW infants at high perinatal risk or with neurological impairment, though minimal association was present for neurologically normal infants at low perinatal risk.

Safety and pharmacokinetics of an intramuscular monoclonal antibody (SB 209763) against respiratory syncytial virus (RSV) in infants and young children at risk for severe RSV disease.

We conducted a multicenter, double-blind, placebo-controlled, randomized trial of a humanized monoclonal antibody against a respiratory syncytial virus (RSV) fusion protein (SB 209763) to evaluate its safety, pharmacokinetics, and fusion inhibition and neutralization titers. Forty-three infants who were either delivered prematurely (

Placental pathology and neurodevelopment of the infant with intrauterine growth restriction.

The placentas of 68 infants with intrauterine growth restriction (IUGR) were examined for evidence of impaired uteroplacental circulation and compared with those of 65 appropriately grown infants. Infarcts and/or accelerated villous maturation were present in the placentas in 27 (40%) of the infants with IUGR compared with seven (11%) of the infants without IUGR (P<0.001). The infants were followed-up at 4 and 12 months of age and growth parameters recorded. Medical and developmental assessments and neuromotor developmental examinations were also performed. The 23 infants in the IUGR group with placentas with evidence of impaired uteroplacental circulation were compared with the 31 infants with IUGR with normal placentas. There was no difference between the groups in growth, cognitive development, or neuromotor abnormality. It was concluded that IUGR is strongly associated with placental markers of impaired uteroplacental blood flow while it would appear that there is no association between placental pathology and growth or neurodevelopment in the first year.

Population pharmacokinetic modeling in very premature infants receiving midazolam during mechanical ventilation: midazolam neonatal pharmacokinetics.

BACKGROUND: Midazolam is used widely as a sedative to facilitate mechanical ventilation. This prospective study investigated the population pharmacokinetics of midazolam in very premature infants. METHODS: Midazolam (100 microg/kg) was administered as a rapid intravenous bolus dose every 4-6 h to 60 very premature neonates with a mean (range) gestational age of 27 weeks (24-31 weeks), a birth weight of 965 g (523-1,470 g), and an age of 4.5 days (2-15 days). A median (range) of four (one to four) blood samples, 0.2 ml each, were drawn at random times after the first dose or during continuous treatment, and concentrations of midazolam in serum were assayed by high-performance liquid chromatography. A population analysis was conducted using a two-compartment pharmacokinetic model using the NONMEM program. RESULTS: Average parameter values (interpatient percent coefficient of variation) for infants with birth weights 1,000 g or less were total systemic clearance (Cl(T)) = 0.783 ml/min (83%), intercompartmental clearance (Cl(Q)) = 6.53 ml/min (116%), volume of distribution of the central compartment (V1) = 473 ml (70%), and volume of distribution of the peripheral compartment (V2) = 513 ml (146%). For infants with birth weights more than 1,000 g they were as follows: Cl(T) = 1.24 ml/min (78%), Cl(Q) = 9.82 ml/min (98%), V1 = 823 ml (43%), and V2 = 1,040 ml (193%). The intrapatient variability (percent coefficient of variation) in the data was 4.5% at the mean concentration midazolam in serum of 121 ng/mL. CONCLUSIONS: Serum concentration-time data were used in modeling the population pharmacokinetics of midazolam in very premature, ventilated neonates. Clearance of midazolam was markedly decreased compared with previous data from term infants and older patients. Infants weighing less than 1,000 g at birth had significantly lower clearance than those weighing more than 1,000 g.

Neonatal neutropenia associated with maternal hypertension poses a risk for nosocomial infection.

UNLABELLED: One hundred and six neonates of 24-32 weeks gestation born to hypertensive mothers and 106 concurrent control infants of normotensive mothers were evaluated to determine the relationship between maternal hypertension and neonatal neutropenia and the risk of nosocomial infection developing in neutropenic infants. Complete blood counts were performed on both cohorts and retrospectively evaluated. Neutropenia was diagnosed using published reference ranges for infants with birth weight <1500 g and > 1500 g. Evidence of nosocomial infection based on a positive blood culture with supportive clinical signs of sepsis was documented. The incidence of neutropenia among infants of hypertensive mothers was not significantly different from that among infants of normotensive mothers (21% vs 24%), but the duration of neutropenia was significantly longer in the infants of hypertensive mothers (P = 0.0001). Nosocomial infection was more frequent in neutropenic than the non-neutropenic hypertensive mothers' infants (55% vs 12%, P = 0.0002). CONCLUSION: Although there is no difference in the incidence of neonatal neutropenia between infants of hypertensive mothers and those of normotensive mothers, the former group has an increased risk of nosocomial infection in neutropenic infants of hypertensive mothers. This may be related to prolonged neutropenia which was found in these infants in the present study.

Maternal hypertension and neurodevelopmental outcome in very preterm infants.

AIM: To determine the outcome of preterm infants born to mothers with hypertension during pregnancy, and preterm controls. METHODS: 107 infants of 24-32 weeks gestation, born to hypertensive mothers, and 107 controls matched for gestational age, sex, and multiple pregnancy, born to normotensive mothers, were prospectively enrolled over 2 years. Information on maternal complications and medication was obtained and neonatal mortality and morbidities recorded. Survivors were followed up to at least 2 years, corrected for prematurity. RESULTS: One third of the hypertensive mothers were treated with antihypertensive drugs, while 18% received convulsion prophylaxis with phenytoin. Magnesium sulphate was not prescribed. Both groups had a mean gestational age of 29.9 weeks, with the study infants having a significantly lower birthweight than the controls. Four study and three control infants died in the neonatal period. Cerebral palsy was not diagnosed in any infant of a hypertensive mother compared with five of the controls. The mean general quotient for the two groups was very similar and no difference in the incidence of minor neuromotor developmental problems was shown. CONCLUSIONS: Maternal hypertension seems to protect against cerebral palsy in preterm infants without increasing the risk of cognitive impairment. This was independent of the use of maternally administered magnesium sulphate.