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Aim: To compare the effects of inhaled and systemic steroids on growth in very low birthweight (VLBW) infants with chronic lung disease (CLD)., Methods: Sixteen babies with CLD randomly received inhaled budesonide (100 microg four times daily for 10 days via Aerochamber) or systemic steroids (dexamethasone 0.5 mg/kg/day, reducing over nine days). Linear growth (lower leg length, LLL) was measured by knemometry twice weekly., Results: The gestational age, birth weight, postnatal age, and LLL velocity (LLLvel) were similar between the two groups at the start of treatment. At the end of the treatment period, LLLvel was reduced in the dexamethasone group (mean -0.01 mm/day) but had increased in the budesonide group (mean 0.48 mm/day). Mean weight gain was non-significantly lower in the dexamethasone group (5.8 g/kg/day) compared to the budesonide group (mean 12.7 g/kg/day)., Conclusion: Inhaled budesonide has less short term effects on growth than systemically administered dexamethasone.

Aims: To evaluate whether serial Doppler measurements of superior mesenteric artery (SMA) blood flow velocity after the first enteral feed could predict early tolerance to enteral feeding in preterm infants., Methods: When clinicians decided to start enteral feeds, Doppler ultrasound blood flow velocity in the SMA was determined before and after a test feed of 0.5 ml milk. The number of days taken for infants to tolerate full enteral feeding (150 ml/kg/day) was recorded., Results: Fourteen infants (group 1) achieved full enteral feeding within seven days. Thirty infants (group 2) took 8-30 days. There was no difference in the preprandial time averaged mean velocity (TAMV) between the groups at a median age of 3 (2-30) days. In group 1, there was a significant increase in TAMV (p<0.01) above the preprandial level at 45 and 60 minutes, but this did not occur in group 2. An increase in TAMV by more than 17% at 60 minutes has a sensitivity of 100% and a specificity of 70% for the prediction of early tolerance to enteral feeds., Conclusions: There is a significant correlation between an increase in mean SMA blood flow velocity and early tolerance of enteral feeding. Doppler measurements of SMA blood flow velocity may be useful for deciding when to feed high risk preterm infants.

The aim of this paper is to determine whether antenatal detection of small-for-gestational-age (SGA) babies influences 2-year outcomes. All low-birth-weight (<2,500g) infants born in South-EastThames region, England from September 1, 1992 to August 31, 1993 were identified at birth. Antenatal "suspicion" and ultrasound assessment confirming growth restriction was categorized as "detection" of SGA. Postnatally, infants were classified as SGA if they had a birth weight for given gestation below the 10th centile. At 2 years, those below 32 weeks' gestation and a random 25% sample of infants of 32 weeks' gestation or more underwent pediatric assessments. Of 49,787 births, 3,456 (6.9%) were of low birth weight. One thousand four hundred and fifty one (42.5%) were SGA, of whom 611 (42%) were detected antenatally by ultrasound scan. At 2 years, 1,008 (75.8%) of 1,358 expected infants were assessed, 379 (37.6%) were SGA at birth, and 188 (49.6%) were confirmed antenatally. Although undetected infants had higher mean birth weights and gestational ages, they had a higher proportion of perinatal deaths (12.6 vs. 6.4%, RR 1.96: CI 1.32-2.86) than detected infants. At 2 years, detected SGA infants had smaller head circumferences (p = 0.026), a higher prevalence of febrile convulsions (8.0 vs. 3.1 %: p = 0.040) and lower scores on the locomotor (DQA) scale of Griffith's developmental test (p = 0.021) compared with undetected SGA infants. Despite detected SGA fetuses having lower weights and gestation at birth than undetected fetuses, they had significantly lower mortality without a parallel increase in severe 2-year neuro-developmental, clinical, or growth morbidity.

A case-controlled study was performed to determine whether preterm premature rupture of the membranes (PPROM), particularly if occurring in the second trimester, increased the duration of ventilatory support or hospital admission. Infants born after membrane rupture of at least 24 hours duration and prior to 37 weeks of gestation were identified. It was possible to match for gestational age and birthweight 40 PPROM infants, 15 of whom had onset of rupture of the membranes (ROM) prior to 27 weeks of gestation, with a control (an infant whose mother had not suffered PPROM). A greater proportion of the mothers of the PPROM infants had received antenatal steroids (p<0.01), had an antepartum hemorrhage (p=0.06) or delivered vaginally (p<0.02). More PPROM infants had pulmonary hypoplasia (p<0.03) or infection (p<0.01). Overall, however, and if only those matched pairs where membrane rupture had occurred prior to 27 weeks of gestation were considered, there were no statistically significant differences in the duration of ventilatory support or hospital admission. Step-wise regression analysis confirmed that in the study population overall and in the matched pairs where membrane rupture had occurred at less than 27 weeks of gestation, neither the duration of ventilation nor hospital admission significantly related to PPROM. These findings have implications when counselling parents.

Human milk is often inadequate nutritionally for preterm infants. We investigated the effect of adding a commercially prepared milk fortifier to human (maternal or bank) milk and measured changes in lower leg length velocity (LLLvel) using knemometry, weight gain and biochemical indices of nutrition. Babies were allocated to one of three feed groups, in a semi-randomized fashion, to receive human milk alone (group I), fortified human milk (group II) or a preterm formula (group III). The birthweights (median and R) and birth gestations (median and R) of the three groups were as follows: group I 1099 g (654-1248 g) and 28 wk (26-32 wk); group II 838 g (742-1340g) and 31 wk (28-36); group III 1136g (624-1552g) and 32 wk (27-36 wk). All babies who received fortified milk either showed significant (p = 0.0004) acceleration in LLLvel during the period studied, or maintained their pre-study period velocity. This increase in LLLvel was comparable to that achieved by a group of babies given a standard preterm infant formula (p < 0.001). By comparison, the control group's change in LLLvel was more modest (p = 0.04). Babies who received human milk with the fortifier added had the lowest serum levels of alkaline phosphatase at the end of the study period when compared to the other two groups. Other biochemical indices were similar in the three feed groups. No adverse clinical events were encountered which could be attributed to the use of the breast milk fortifier.

Unlabelled: Theophylline administration has been shown to attenuate erythropoietin (EP) production in adults; the effect of caffeine is not known. Our aim was to determine whether caffeine and theophylline had similar effects on EP production in the premature newborn. If caffeine was found to have a greater effect, this would influence prescribing habits. Fifty preterm infants (mean gestational age 28 weeks) who had clinically significant apnoea were randomized to receive theophylline (4 mg/kg then 2 mg/kg twice daily) or caffeine (10 mg/kg then 2.5 mg/kg once daily). The methylxanthines were continued at least until discharge from the NICU and the dosage altered to keep the levels within the therapeutic range. As an assessment of EP production, serum EP concentrations were measured. Blood for EP, haemoglobin, reticulocyte count, theophylline and caffeine levels was obtained prior to treatment and at least during weeks 3 and 7. There was no significant difference in the mean EP level in the two groups taken prior to treatment at a median age of 2 days of life. There were similar falls in haematocrit and haemoglobin in the two groups during the study period compared to pre-treatment values. At that time, however, the median reticulocyte count was higher in the caffeine compared to the theophylline treated infants (P < 0.05). This was associated with a rise compared to baseline (median 10.0-0.2 mU/ml) in the mean EP levels in the caffeine group and a decrease from a median of 10.1 to 8.3 mU/ml in the theophylline group, but the EP levels in the two groups at week 7 did not differ significantly., Conclusion: These results suggest that caffeine does not have a greater impact than theophylline on EP production.

Objective: To document perinatal changes in cerebral and renal artery haemodynamics in premature growth-retarded and normal term infants., Design: Longitudinal study of individual infants. Doppler ultrasound measurements of blood flow velocity (BFV) in the middle cerebral and renal arteries were obtained before delivery, soon after delivery and during the first week of postnatal life., Setting: Teaching hospital obstetric and neonatal units., Subjects: 13 severely growth retarded infants born at 28-36 weeks gestation, and eight normally grown infants born at term., Results: In both groups, BFV in the cerebral artery was significantly lower in the first few hours after birth than in fetal life, but subsequently increased to reach pre-delivery values by the end of the first week. In contrast, BFV in the renal artery during the first postnatal day was not significantly different from fetal values, but it also increased during the subsequent week. In six of the preterm growth-retarded infants, fetal blood gases were measured in samples obtained by cordocentesis, and in these cases an increase in blood oxygen content at birth was documented., Conclusions: Cerebral artery BFV falls at birth and is relatively low during the time that premature infants are at the greatest risk of developing periventricular haemorrhage.

This study examines the effect of pregnancy on fetal outcome and maternal renal function in 17 women with Type 1 diabetes mellitus and nephropathy attending a joint diabetic-antenatal clinic between 1985 and 1993. There were 7 successful pregnancies in 6 women with moderate renal impairment, mean pre-pregnancy serum creatinine 165 mumol l-1 (Group 1), and 12 in 11 women with proteinuria and preserved renal function (Group 2). Median gestation of pregnancy was 31 + 3 weeks in Group 1 and 36 + 4 weeks in Group 2 (p < 0.05). All babies in Group 1 required neonatal intensive care for a median of 19 days (range 8-271) as compared to only 5 of 13 in Group 2 whose median stay was 13 (7-17) days (p < 0.05). There was one late death in Group 1. Longitudinal creatinine data in those with moderate renal impairment suggest no systematic adverse long-term effect of pregnancy on maternal renal function, although differing changes in renal function were observed during pregnancy. The generally favourable outcome achieved relied heavily upon neonatal care expertise.

Congenital diaphragmatic hernia is associated with significant mortality and morbidity. The aim of this study was to compare a series of tests with respect to prediction of outcome. Tidal volume and compliance of the respiratory system (CRS) were measured preoperatively and on the first and second postoperative days. The maximum and modified ventilation indexes and the maximum Paco2 were noted for the first 6 hours of life and the first 6 hours postoperatively. In addition, it was recorded whether the stomach was within the ipsilateral hemithorax preoperatively. Twenty infants were studied (median gestational age, 38 weeks; range, 31 to 40), six of whom had a poor outcome, ie, they died or remained oxygen-dependent after 28 days. A CRS of less than 0.18 mL/cm H2O/kg was the most accurate predictor of poor outcome, with 66% sensitivity and 100% specificity. The authors conclude that lung function measurement are useful in the assessment of infants with congenital diaphragmatic hernia.

Confidential enquiry into stillbirth and death in infancy is a health service requirement in England, Wales and Northern Ireland. A confidential review of perinatal death has been conducted in South-East Thames Region since 1988. Data collected for this review are analysed here. Among the 1662 singleton deaths in the enquiry from 1988 to 1991, 530 (32%) babies were small for gestational age (SGA < 10th centile): 338 of these (64%) were < 3rd centile and the remainder were between 3rd-10th centile. Small size for gestational age was significantly associated with a previous SGA baby (P = 0.02), proteinuric hypertension (P = 0.001) and increased placental-birthweight ratio (P = 0.008). Only 135 (25%) SGA fetuses were identified antenatally and multiple logistic regression showed that antenatal detection was independently related to proteinuric hypertension [odds ratio (OR) = 2.47, 95% confidence interval (CI) 1.47-4.17, P = 0.001) and to being < 3rd centile rather than 3rd-10th centile (OR = 3.16, 95% CI 1.96-5.10, P = 0.001). Although confidential enquiries have been criticised for a lack of objectivity the study indicates how data from such an enquiry can increase knowledge of events influencing peri- and neonatal outcome allowing strategies to be devised to effect change.

A prospective study of the outcome of care of a regional cohort of very low birthweight (< 1500 g) and very preterm (< 32 weeks) infants was carried out. Its aims were to assess the ability of the CRIB (clinical risk index for babies) score, rather than gestational age or birthweight, to predict mortality before hospital discharge, neurological morbidity, and length of stay, and to access CRIB score as an indicator of neonatal intensive care performance. 676 live births fulfilled the criteria and complete data were available for 643 (95%). Compared with gestation and birthweight, CRIB was better for the prediction of mortality, was as good for the prediction of morbidity, and was not as good for the prediction of length of stay. CRIB adjusted mortality did not demonstrate better performance in units providing the highest level of care. Either the CRIB score was not sensitive to performance or the level 3 hospitals in this study were performing badly. On the basis of this analysis purchasers and providers of neonatal intensive care cannot yet rely on the CRIB score as a performance indicator.

Objectives: To assess the contribution of children with different birth weights to special educational needs within a single health district, and to determine whether this pattern changed over the time when the survival of very low birthweight (VLBW) infants was increasing., Setting: An inner London health district., Study Design: A cohort of children born to local parents between January 1974 and December 1980 was selected from birth notifications, including only those infants who survived for more than one month. Community child health records were then inspected to identify children from the cohort who had been formally assessed for special educational needs before their 8th birthday. The risk of special educational needs was compared for the years 1974-77 and 1977-80 (the first and second halves of the period studied)., Subjects: The infant cohort consisted of 31,846 children. Altogether 260 (0.8%) of these were later assessed formally., Results: VLBW infants were 4.4 times more likely to be assessed than normal birthweight infants. Formal assessment within the district occurred in three of 68 VLBW infants from the first half of the period studied, and three of 120 from the second half., Conclusion: Although VLBW infants are at higher risk, an increase in their survival was not associated with any increase in their contribution to the group with special educational needs within our district. Their contribution, as a group, to the total number of children with special educational needs is very small.

This study aimed to determine if fetal bacteraemia and amniotic fluid infection at the time of membrane rupture reduces the interval between membrane rupture and the onset of labour in pregnancies complicated by preterm prelabour amniorrhexis. Sixty nine pregnancies with preterm prelabour amniorrhexis at 12-36 weeks' gestation that were managed expectantly had spontaneous onset of labour. In all cases cordocentesis and amniocentesis were performed and fetal blood and amniotic fluid were cultured for aerobic and anaerobic bacteria. In the group with negative fetal blood and amniotic fluid cultures (group 1) the median interval from amniorrhexis to delivery was 41 days (range 1-161) and there was an inverse correlation between gestational age at amniorrhexis and delivery interval. In the group with negative fetal blood but positive amniotic fluid cultures (group 2) the median amniorrhexis to delivery interval was nine days (range 1-37), and in the group with positive fetal blood cultures (group 3) the interval was two days (range 1-5). These findings suggest that pregnancies complicated by preterm prelabour amniorrhexis and fetal bacteraemia undergo spontaneous labour within five days of membrane rupture, and if labour does not occur then infection is unlikely.

An infant with intrathoracic extra-mediastinal cystic hygroma is described. Fluid collection within the fetal chest was noted on routine antenatal ultrasound scan and this was subsequently drained. Postnatally, echocardiogram and thoracic CT scan demonstrated a cystic space between the pericardium and right mediastinal pleura. Thoracotomy performed at six weeks of age showed a multiloculated cystic mass adherent to the right pericardium and to the medial aspect of the diaphragm. Histology revealed the tumour to be a cystic hygroma (lymphangioma). Intrathoracic cystic hygroma occurring outside the mediastinum is extremely rare and has never been diagnosed previously in infancy.

Fresh frozen plasma and intravenous immunoglobulin are used as prophylaxis against, and for the treatment of, neonatal infection. It is assumed that any beneficial effect is mediated through the humoral immune factors contained in each preparation. The effect of fresh frozen plasma and intravenous immunoglobulin on humoral immune markers (immunoglobulins and IgG subclasses, complement components and activation products, and C reactive protein) was investigated over a 24 hour period after their randomised administration to 67 infants with suspected infection. Thirty infants without suspicion of infection were studied as controls. Compared with control infants, infants with suspected infection had increased concentrations of C reactive protein, reduced concentrations of fibronectin, and increased concentrations of the complement activation marker C3d, but similar concentrations of IgG, IgG subclasses, IgA, and IgM. After intravenous immunoglobulin treatment (500 mg/kg) concentrations of total IgG and all IgG subclasses increased, as did IgA and complement component C4. Concentrations of C reactive protein decreased after intravenous immunoglobulin treatment and were significantly lower than baseline after 24 hours. In contrast, no change in IgG or IgG subclass concentrations occurred after fresh frozen plasma administration. At 24 hours after fresh frozen plasma administration, concentrations of IgA, IgM, and C4 were significantly higher than baseline and serum IgA was significantly higher than in infants tested 24 hours after intravenous immunoglobulin treatment. These results confirm the rational basis for intravenous immunoglobulin treatment but question the value of fresh frozen plasma, particularly in the light of its attendant problems as an untreated blood product.

High frequency oscillation (HFO) as rescue treatment for preterm infants with severe respiratory failure has been assessed and prognostic factors identified. Thirty six infants with a median gestational age of 27 weeks were studied. Immediately before transfer to HFO, the infants were receiving an inspired oxygen concentration of > or = 85% and/or a mean airway pressure of > or = 12 cm H2O and had a median alveolar-arterial oxygen gradient (A-aDO2) of 73.28 kPa (range 49.34-89.91). Seventeen infants subsequently died. Comparison of those 17 with the remaining 19 infants demonstrated that respiratory distress syndrome and persistent fetal circulation were associated with a significantly better outcome than pulmonary airleak. The A-aDO2 after two and six hours on HFO was significantly higher in those infants who survived compared with those who died. We conclude that a diagnosis of pulmonary airleak and failure to show early improvement in respiratory status indicate a poor prognosis when HFO is used as rescue treatment.

Respiratory morbidity in the first 6 months of life of 35 infants who had had neonatal meconium aspiration syndrome (MAS) was compared to that of 70 controls, also born at term, matched for gender and ethnic origin. The number of infants in the two groups who were symptomatic was compared. Infants were described as symptomatic if, following discharge from hospital, they had at least one episode of wheezing and/or coughing which lasted for 3 days or more. There was no significant difference between the two groups regarding parental smoking or the proportion of infants who had a family history of atopy. A significantly greater proportion of the MAS group (49%) than of the control group (20%) was symptomatic at follow-up. Eight (23%) infants with MAS and 2 (3%) controls had symptoms which necessitated regular bronchodilator therapy. The 8 infants with MAS who were on maintenance bronchodilator therapy had required significantly longer neonatal respiratory support and had larger lung volumes at follow-up than the other 27 infants. We conclude that neonatal meconium aspiration syndrome is associated with increased respiratory morbidity in the first 6 months of life.

To compare the effects of acute changes in blood pressure on arterial blood flow velocity in various regional circulations, Doppler ultrasound measurements of blood flow velocity were recorded from the anterior cerebral artery (ACA), superior mesenteric artery, coeliac axis and left renal artery. Measurements were obtained from 10 ventilated very low birth weight infants before and after plasma infusions given to treat systemic hypotension on the first day of postnatal life. Blood pressure increased in 8/10 infants, and in this group there was a significant increase in ACA and coeliac axis blood flow velocity. For the ACA only, there was a significant association between the change in blood flow velocity and the magnitude of the change in blood pressure (r = 0.73, P < 0.02). Mesenteric and renal artery velocity did not increase after the infusion. For ventilated VLBW infants on the first day of life, arterial blood flow velocity was affected by acute changes in blood pressure in the cerebral circulation only.

In order to determine the relationship between blood pressure and arterial blood flow velocity in various regional circulations, Doppler ultrasound measurements of blood flow velocity were recorded on the first day of postnatal life from the anterior cerebral (ACA), superior mesenteric, coeliac axis and left renal artery. In 34 ventilated very low birth weight (VLBW) infants, results were correlated with arterial blood pressure and blood gases in a multiple regression model. ACA velocity was correlated with blood pressure (r = 0.70) and PaCO2 (r = 0.64), but there was no relationship between blood pressure and velocity in the other arteries. Repeated measurements were performed at one week of age in 15 infants. Blood flow velocity in the cerebral and renal arteries was related to blood pressure; velocity in the cerebral arteries was inversely correlated with PaO2 and velocity in the coeliac and mesenteric arteries was positively correlated with PaO2. In VLBW infants on the first day of life, blood flow velocity is related to blood pressure in the cerebral circulation only.

Doppler ultrasound was used to measure blood flow velocity in the anterior cerebral artery of six premature infants with posthaemorrhagic hydrocephalus, before and after intermittent cerebrospinal fluid (CSF) drainage, on 23 occasions. There was a significant increase in mean blood flow velocity after the drainage procedures (+5.6 cm/s, 95% confidence interval +2.9 to +8.3 cm/s), which was accompanied by a decrease in velocity waveform pulsatility. CSF pressure also fell significantly. In patients with posthaemorrhagic hydrocephalus, intermittent CSF drainage was associated with acute changes in cerebral haemodynamics.

Doppler ultrasound was used to measure left renal artery blood flow velocity and pulsatility index on the first, third, and seventh day of postnatal life in 18 very low birthweight small for gestational age (SGA) infants. The values were compared with those from 18 weight matched and 18 gestation matched controls. SGA infants had significantly lower blood flow velocity than their gestation matched controls throughout the first postnatal week (day 1: SGA 10 cm/s, controls 15 cm/s; day 7: SGA 17 cm/s, controls 28 cm/s). These data suggest that abnormalities of renal artery blood flow velocity persist after delivery in the SGA infant.

Respiratory function was assessed at a median of 7 months (range 6-12) in 17 preterm infants who, in the neonatal period, had been entered into a multi-centre randomized placebo-controlled trial of prophylactic surfactant replacement therapy. Seven infants (median gestational age 28 weeks) received surfactant and the remaining ten infants (median gestational age 27 weeks) placebo. Respiratory function was assessed by measuring functional residual capacity (FRC), thoracic gas volume (TGV) and airways resistance (RAW). Specific conductance (SGAW) was calculated from RAW and TGV. There was no significant difference in FRC or TGV between the two groups. RAW, however, was significantly lower in the surfactant (median 41, range 21-48 cmH2O l-1 s-1) compared to the placebo group (median 57, range 40-68 cmH2O l-1 s-1), P < 0.05 and SGAW significantly higher in the surfactant (median 0.136, range 0.063-0.289 l cmH2O-1 s-1) compared to the placebo group (median 0.081, range 0.062-0.134 l cmH2O-1 s-1), P < 0.05. These results suggest that surfactant replacement therapy improves lung function at follow-up.

The effect of dexamethasone therapy on fluid balance, lung function and requirement for respiratory support has been assessed. Ten premature infants were studied, they had a median gestational age of 28 weeks. None of the infants had any improvement in the respiratory status for 48 h prior to commencing dexamethasone. Fluid balance, pulmonary function and requirement for respiratory support were measured 12 h prior to and for 36 h after receiving dexamethasone. There were no significant changes in fluid input over the study period, but urine output increased significantly after 12 h of dexamethasone therapy (P < 0.02). Compliance of the respiratory system only significantly improved after 36 h of dexamethasone therapy (P < 0.03), this was associated with a significant change in the inspired oxygen concentration (P < 0.05). We conclude that the improvement in respiratory status resulting from dexamethasone therapy is preceded by a diuresis.

In order to determine if umbilical arterial catheter position affects the incidence of necrotizing enterocolitis, clinical outcome was analysed in 308 infants whose umbilical arterial catheter had been randomly allocated to a high (n = 162) or a low (n = 146) position. Necrotizing enterocolitis was classified as suspected or confirmed; all renal, lower limb and local catheter complications were also recorded. High umbilical arterial catheters were in place for longer than low catheters, provided more samples and were removed as an emergency less often. Lower limb blanching and cyanosis were more common with low catheters. Eleven cases of confirmed necrotizing enterocolitis occurred in the "high" group and nine in the "low" group. One case of fatal aortic thrombosis was encountered in the high group. Positioning umbilical arterial catheters in a high position allowed longer functional use and did not increase the incidence of necrotizing enterocolitis.

We assessed the effect of albumin infusion on weight loss and ventilation requirement in sick premature infants. Thirty infants, median gestational age 29 weeks, were entered into a randomised controlled trial, at a median of 2 days of age. The infants, all with an albumin level < or = 30 g/l, received either 5 ml/kg of 20% albumin or 5 ml/kg of their maintenance fluids (placebo), both given as part of the total daily fluid requirement. The response to the infusion was assessed by comparing two periods; 12 h immediately prior to the infusion and 12-24 h after the infusion. Albumin infusion was associated with a significant increase in albumin level and a significant reduction in weight, but in the placebo group there was a significant increase in weight. There were, however, no significant changes in the peak inspiratory pressure in response to either infusion. There was only a modest reduction (< 15%) in the inspired oxygen concentration, which occurred in both groups, but reached statistical significance only following the albumin infusion. We conclude that our results suggest that albumin infusion in "hypoalbuminaemic" sick preterm infants is unlikely to alter their respiratory status.

The records of 15 cases of hydrops fetalis consecutively delivered at our institution were reviewed to determine the accuracy of antenatal diagnosis and whether antenatal diagnostic techniques yielded information useful in predicting outcome. All 15 cases were detected antenatally, five were due to rhesus haemolytic disease and 10 were non-immune hydrops. All the infants required active resuscitation. Ten infants eventually died, two had immune hydrops fetalis and 8 non-immune hydrops. Seven infants had pleural effusions, all had been detected antenatally. The presence of pleural effusions did not influence mortality. All structural abnormalities were accurately detected in those patients seen prior to labour and there were no survivors in the group of infants so affected. We conclude that the mortality of non-immune hydrops fetalis remains high and that antenatal diagnosis of this condition is accurate and provides useful prognostic information.

Vitamin A status was determined in infants born at term or prematurely to assess if vitamin A levels at birth were related to gestational age. Vitamin A levels were measured in cord blood samples from 13 infants born at term and in blood samples obtained within two hours of birth in 26 preterm infants (median gestational age 31 weeks, range 27-35). None of the preterm infants developed chronic lung disease. The vitamin A levels of the term infants (median 0.71 mumol/l, range 0.34 to 1.27) were significantly higher than those of infants born preterm (median 0.35 mumol/l, range 0.12 to 1.22), p < 0.01. Vitamin A levels correlated significantly with gestational age (vitamin A level = 0.024 gestational age (weeks) -0.23, r = 0.39, p < 0.02. We thus conclude that gestational age must be taken into account when interpreting vitamin A levels.

Infants with chronic lung disease (CLD) have been demonstrated to have low vitamin A levels. The aim of this study was to assess factors which influenced this association. Vitamin A levels of infants born at less than 32 weeks gestational age with and without CLD were determined and related to feeding practice. The infants with CLD had statistically significantly lower vitamin A levels on days 21 to 30 and days 31 to 40. From day 11 onwards, the median Vitamin A levels were less than 60% of the minimum acceptable level for a healthy child or adult. Infants with CLD required significantly longer mechanical ventilation and parenteral nutrition than controls and there was a significant positive correlation between duration of mechanical ventilation and parenteral nutrition (r = 0.83). Infants with CLD received significantly less vitamin A supplementation than the infants without CLD. Our results thus suggest that feeding practice explains the association of CLD and vitamin A deficiency in preterm infants.

Vitamin A levels were measured shortly after birth in preterm infants at high risk of developing chronic lung disease (CLD). Eleven infants, median gestational age 24 weeks, developed CLD. Their results were compared to 11 infants who, although they required mechanical ventilation for at least 48 hours, did not develop CLD. The median gestational age of this latter group was 30 weeks (range 27-35). The median vitamin A level of the infants who developed CLD was 0.62 umol/l (range 0.41-0.95), which was significantly higher than the median level of the infants who did not develop CLD, which was 0.36 umol/l (range 0.13-0.89). We conclude preterm infants who develop CLD are not predisposed to develop that complication by low vitamin A levels at birth.

Colloid infusions are often given to treat hypotension in preterm infants. The aim of this work was to assess whether it was the amount of protein or the volume of the colloid infused which accounted for the observed increase in blood pressure. Sixty preterm infants were randomised (20 in each group) to receive 5 ml/kg 20% albumin, 15 ml/kg fresh frozen plasma, or 15 ml/kg 4.5% albumin. All infusions were given at a rate of 5 ml/kg/hour in addition to maintenance fluids. The infants were randomised when hypotensive (systolic blood pressure less than 40 mm Hg for two hours). There was no significant difference in the blood pressure of the three groups before or one hour after beginning the infusion. The mean increase in blood pressure one hour after completing the infusion, however, was significantly lower in infants receiving 20% albumin: 9% compared with 17% in the group receiving 4.5% albumin, and 19% in the group receiving fresh frozen plasma. It is concluded that the volume infused rather than albumin load is important in producing a sustained increase in blood pressure.

Previous data have suggested that neonatal complications amongst preterm ventilated infants increase with decreasing gestational age and thus are likely to be greatest among ventilated infants of less than 28 weeks gestational age. The aim of this study was to test that hypothesis, thus we report the neonatal complications of 175 extremely preterm mechanically ventilated infants (gestational age less than or equal to 28 weeks). Of the infants 152 were ventilated because of respiratory distress syndrome (RDS) or respiratory distress of severe prematurity, 41% of these infants died. Amongst infants with RDS or respiratory distress of extreme prematurity, mortality was significantly increased in infants of gestational age less than or equal to 24 weeks and birth weight less than or equal to 1000 g. In this group 20% developed a pneumothorax, and mortality was inversely related to gestational age. In infants with RDS, 43% developed a periventricular haemorrhage and 37% were still oxygen-dependent at 28 days of age; neither of these complications was significantly related to birth weight or gestational age. Of infants with RDS 38% developed a patent ductus arteriosus and 16% developed retinopathy of prematurity. These data suggest that even amongst very immature infants there has been an impressive reduction in the neonatal complications of mechanical ventilation.

To investigate the usefulness of indices of complement activation in the diagnosis of infections in the neonatal period, activation products C4d, Ba, and C3d were measured in 42 babies with a putative diagnosis of infection based on clinical/laboratory criteria, and compared with conventional clinical and haematological criteria of infection and with C reactive protein. The diagnosis of sepsis was confirmed by culture and identification of organisms in 17. Fourteen babies in whom infection was not suspected formed the control group. In babies with proved infection, concentrations of the fragments C4d, Ba, and C3d were higher than in babies with suspected infection in whom microbiological tests were negative, and concentrations of Ba and C3d were higher than in controls. C reactive protein and the platelet count were not significantly different in babies with proved infection and those with negative microbiological tests, but in the latter, C reactive protein concentrations were higher than in controls. Of the indices studied, high concentrations of Ba predicted microbiologically proved infection with the highest sensitivity (47.1%) and specificity (92.0%). Ba thus seems to be useful as an early indicator of infection in the neonatal period.

Umbilical arterial catheters (UAC) were randomly assigned in 69 infants to a high (n = 36) or to a low (n = 33) position. Serial Doppler ultrasound measurements of blood flow velocity in their superior mesenteric arteries, coeliac axis, renal arteries, and anterior cerebral arteries were then obtained. There were no differences in blood flow velocity between high and low UAC groups on days 1, 3, and 7. At 2 weeks, those infants with a high UAC still in place had significantly higher velocities in the mesenteric artery than those infants who had no catheter in place. Infants with high UACs remaining in place for more than 7 days were found to have an increase in abdominal distension and tenderness, whereas this was not the case for those with low UACs. Catheter position has no effect on visceral blood flow if the UAC stays in place for one week or less, whereas prolonged use of a high UAC may alter intestinal blood flow and increase the incidence of abdominal symptoms.

Doppler measurements of blood flow velocity were obtained from the superior mesenteric artery (SMA), coeliac axis, and anterior cerebral artery (ACA) of 19 infants with suspected necrotising enterocolitis, which was classified as confirmed (n = 9) or unconfirmed (n = 8). Infants with confirmed disease were compared with controls who were either enterally fed or who were receiving intravenous fluids. SMA velocity was significantly higher in the infants with confirmed necrotising enterocolitis (36.5 cm/s) than in unfed controls (20.4 cm/s) or infants with unconfirmed enterocolitis (19.6 cm/s). Three infants with confirmed disease had data from before the onset of symptoms. One had low SMA velocity on the first day of life, and one showed no increase in SMA velocity after enteral feeds were started. SMA velocity is increased when infants develop symptoms of necrotising enterocolitis, suggesting that total gut ischaemia is not present at the time that the disease is clinically apparent, although it may precede the onset of symptoms and play a part in the pathogenesis of the disorder.

Neonatal ventilatory requirements and outcome were examined in 135 very preterm, small-for-gestational age (SGA) infants to determine whether fetal growth retardation protects against severe respiratory distress syndrome (RDS) in very immature infants. Their results were compared to those from gestational age- and gender-matched controls. Although there was no significant difference in the median duration of mechanical ventilation between the two groups, more SGA infants required ventilation and were ventilated because of RDS. In a subgroup also matched for mode of delivery, there was no significant difference between the proportion of SGA infants requiring mechanical ventilation for RDS compared to their matched controls. The mortality was greater in the SGA group. We conclude that fetal growth retardation does not protect against severe RDS.

The occurrence of congenital and nosocomial bacterial septicaemia has been documented by identifying the number of positive blood cultures by reviewing the laboratory and clinical records of 394 very low birth weight infants who were consecutively admitted to a neonatal intensive care unit over a 40-month period. The incidence of congenital septicaemia was 6% and of nosocomial septicaemia 17%. The commonest causes of congenital infection were Streptococcus agalactiae Staphylococcus epidermidis and Enterococcus faecalis (each in 18% of cases). The commonest cause of nosocomial infection was S. epidermidis (51% of cases), except in infants of birth weight less than 750 g. Risk factors for nosocomial infection were extremely low birth weight, very preterm birth and prolonged ventilation. Nosocomial infection was associated with significantly lengthened hospital admission.

The magnitude and duration of the effect of dexamethasone on systolic blood pressure has been examined in 13 very preterm infants (median gestational age 25 weeks). All had chronic lung disease (CLD). To exclude any effect of CLD on blood pressure each infant acted as his or her own control. Systolic blood pressure increased in all infants (P less than 0.01) and remained elevated for at least 48h following cessation of therapy. The median maximum increase in blood pressure was 24 mmHg (range 13-49 mmHg) and occurred on day 4 (median, range 2-10) of treatment. One infant developed hypertensive encephalopathy. These results demonstrate the need to monitor infants with CLD throughout steroid therapy and preferably for some days after it has ceased.

The results of body fluid and surface cultures from 148 preterm infants less than 33 weeks gestational age obtained routinely on admission to a neonatal intensive care unit were reviewed. The aim was to determine the occurrence of congenital bacterial sepsis in this population and to examine whether surface cultures yielded information helpful in management. Gastric aspirate and umbilical, nasal and ear swabs were cultured and the results were compared to those of blood cultures. Nine infants (5.4%) had congenital bacterial sepsis diagnosed by positive blood cultures. Only the results of microscopy of gastric aspirate were available within hours of birth and before the results of blood culture. Microscopy of gastric aspirate, demonstrating pus cells, alone had a sensitivity of 0.86 in predicting congenital sepsis but a specificity of 0.49; the specificity, however, rose to 0.80 if both organisms and pus cells were observed on microscopy. Thus, only this combination was a useful pre-indicator of congenital sepsis. In infants who did not develop septicaemia, treatment was modified only if Streptococcus agalactiae was cultured from surface sites; in all such cases, the organism was grown from the ear swab. Our results demonstrate that congenital bacterial sepsis is common amongst very preterm infants admitted for neonatal intensive care but routine screening of surface cultures should be restricted to an ear swab only.

Salbutamol infusion, 4 micrograms/kg in 5 ml of water infused for 20 minutes, was given to treat hyperkalaemia (potassium level > 6.0 mmol/l) in 10 critically ill preterm infants (median gestational age 26 weeks). Seven infants had acute renal failure, two had persistent metabolic acidosis without renal failure and the remaining infant had a combination of acute renal failure and persistent metabolic acidosis. No infant developed a tachycardia or became hyperglycaemic in response to the infusion. Seven of the 10 infants ultimately died but this was at a mean of 9 days following the infusion and as a consequence of complications due to their extreme prematurity or major congenital abnormality. In response to the infusion the potassium level fell in 7 infants with acute renal failure by a median of 1.1 mmol/l (range 0.7-1.8) at one hour but in the three infants with a persistent metabolic acidosis, the potassium level continued to rise. We conclude that salbutamol infusion achieves, without side-effects, at least a temporary reduction in hyperkalaemia in preterm infants with renal failure, but not metabolic acidosis. Its effect is of sufficient duration to allow ample time for definitive therapy to be instituted and thus may be a useful alternative for infants in whom the possible hypoglycaemic side-effects of glucose and insulin should be avoided.

Blood flow velocity and pulsatility index were measured with Doppler ultrasound in the superior mesenteric artery, coeliac axis, and anterior cerebral artery in 18 very low birth weight, small for gestational age infants, and compared with findings from 18 weight matched, and 18 gestation matched, appropriate for gestational age controls. Mean velocity in the superior mesenteric artery was lower in the small for gestational age infants (15 cm/s) than in the gestation matched control group (20.4 cm/s). In those small for gestational age infants who had evidence of fetal hypoxia the mean velocity in the superior mesenteric artery was even lower (11.5 cm/s). There were no differences in velocity in the cerebral artery among the groups. Infants who were small for gestational age still had significantly lower superior mesenteric artery velocity than gestation matched controls at 1 week of age. The results suggest a specific reduction in visceral perfusion in infants who are small for gestational age and who have experienced fetal hypoxia, and this could predispose these infants to necrotising enterocolitis.

The magnitude of inflating pressure necessary for effective resuscitation was examined in 70 preterm infants. The median pressure to cause adequate chest wall expansion was 22.8 cmH2O; no infant required a peak inflating pressure greater than 30 cmH2O. No further increase in inflation pressure was used during resuscitation and the median 5- and 10-min Apgar scores were 8 and 9, respectively.

In a 12-month period 28 of 164 consecutive very low birthweight (VLBW) infants receiving intensive care within 48 h of birth at King's College Hospital developed chronic lung disease, (oxygen dependence beyond 28 days of age). Fifteen of the 28 infants were eligible for home oxygen therapy, but this was only practical, because of home circumstances, in 8 infants (4.9%). These 8 infants received home oxygen therapy. One further infant, born at term and suffering from pulmonary hypoplasia was also discharged home on oxygen therapy. Two infants subsequently required readmission due to a deterioration in their respiratory status and died. Three others required re-admissions (total duration 32 days) for respiratory problems. The median duration of home oxygen therapy was 17 weeks (range 4-486 days). We conclude that home oxygen therapy is needed by only a very small number of preterm infants and is appropriate for only a proportion of them. Parents need to be counselled carefully regarding the possibility that the need for oxygen might be protracted.

Despite postmortem and clinical studies, the etiological factors that determine why only a proportion of intubated neonates develop subglottic stenosis remain unclear. This prospective study was initiated to identify factors that were associated with laryngeal abnormalities secondary to intubation. Thirty neonates were examined at extubation by two independent observers blinded to the neonate's ventilatory history. Thirty-six possible prognostic indicators were recorded for each neonate. After screening by univariate (chi 2) analysis, 10 indicators were selected for further analysis. Of these 10 selected only two indicators showed an association with the laryngeal appearance. Active neonates had significantly more abnormalities in the supraglottis (P = 0.004) than those who were quiescent. Younger neonates had more abnormalities in the glottis though the significance level was marginal (P = 0.056). Other prognostic indicators, including birthweight, gestational age, duration of intubation and frequency of intubation, were not significantly related to laryngeal appearance. This study supports the hypothesis that the etiology of laryngotracheal stenosis is multifactorial, and has identified two possible etiological factors: age and neonatal activity. Neonatal activity has not been identified previously as an etiological factor. The contribution of individual factors may vary from one neonatal unit to another, as a result of variation in intubation, ventilation and extubation policy. This could explain the inconsistency in etiological factors identified by previous studies. It is therefore not yet possible to recommend a standard technique for the ventilation of premature neonates that would further reduce the incidence of laryngotracheal stenosis.

Inspiratory and expiratory volumes were measured in 51 preterm infants with respiratory distress syndrome (RDS), when comparing two ventilator rates, 60 and 120 breaths/min. Gas trapping was not demonstrated at rates of 60, but in 11 infants at 120 breaths/min and this was more common in the paralysed infants and those more mature than 31 weeks gestational age (P less than 0.05). The median change in functional residual capacity resulting from gas trapping was 3.8 ml/kg. We conclude rates of 120 breaths/min can be used in the majority of non-paralysed infants without gas trapping but should be avoided in paralysed infants more mature than 31 weeks.

The clinical course and outcome is described of three pregnancies complicated by listeriosis encountered during a 6-month period. All three ended in preterm labour characterized by the passage of meconium by the fetus. Two babies died in the early neonatal period and the third survived with neurological handicap. Although the diagnosis of listeriosis was made only after delivery, all the mothers had a pyrexial illness before delivery. A high index of suspicion is needed for the early detection and prompt treatment of this life-threatening perinatal infection. Effective advice concerning prevention of listeriosis by avoidance of high-risk foods must be given to women during pregnancy.

Twenty-five severely rhesus-isoimmunized fetuses, including 15 with hydrops fetalis, underwent a total of 77 intrauterine transfusions between 19 and 32 weeks' gestation. Fifty-eight of the procedures were fetoscopically directed intravascular transfusions, nine were ultrasound-guided intraperitoneal transfusions, and 10 were a combination of intravascular transfusion, fetal paracentesis, and intraperitoneal transfusion. The average number of antenatal procedures per patient was three (range, one to five). The survival rate for the 19 fetuses that received their initial intrauterine transfusion at or before 25 weeks' gestation was 84%; 11 of the 13 hydropic fetuses and five of the six fetuses without antenatal evidence of hydrops survived. In six cases hydrops fetalis was reversed in utero. The outcome in patients referred after 25 weeks' gestation was poor; neither of the two hydropic fetuses and only two of the four nonhydropic ones survived, which suggests the importance of early referral to a team experienced in the management of this problem. However, most of these fetal losses occurred early in the series. Seven of the 20 neonates were hydropic, and nine had severe thrombocytopenia (platelet count, less than 50,000 X 10(6)/L). The mean cord blood hematocrit and bilirubin of the neonates were 25.1% and 82 mumol/L, respectively. The babies required a total of 69 exchange transfusions (range, 0 to 9) and 68 simple transfusions (range, 0 to 25). One newborn infant who had had ultrasound evidence of hydrops fetalis at 22 weeks' gestation did not require any exchange transfusions. Nine patients required intermittent positive pressure ventilation (eight had respiratory distress syndrome and one had apnea) for a range of 1 to 86 days. The neonatal survival rate was 90% (18/20).

The labours of 8 patients which resulted in the birth of babies with brachial plexus injury were studied. Four of the mothers were Black, 1 was Asian and 3 were White. Seven had instrumental deliveries. All babies were above average birth weight. Shoulder dystocia occurred in 7, with 5 of these showing abnormal partographic patterns. The abnormal active phase on the partogram should serve as a first stage warning of the possibility of shoulder dystocia. Methods of management of this second stage complication are reviewed.