Growth effects of systemic versus inhaled steroids in chronic lung disease.

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.

Prediction of early tolerance to enteral feeding in preterm infants by measurement of superior mesenteric artery blood flow velocity.

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.

Does the antenatal detection of small-for-gestational-age babies influence their two-year outcomes?

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.

Changes in growth and metabolism in very low birthweight infants fed with fortified breast milk.

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.

Neonatal outcome following early onset preterm premature rupture of the membranes--a case controlled study.

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.

Comparison of the effects of theophylline and caffeine on serum erythropoietin concentration in premature infants.

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.

Cerebral and renal artery blood flow velocity before and after birth.

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.

Outcome of pregnancy in patients with insulin-dependent diabetes mellitus and nephropathy with moderate renal impairment.

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.

Prognostic indicators in congenital diaphragmatic hernia.

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.

The association between small size for gestational age and perinatal and neonatal death in a UK Regional Health Authority.

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.

Use of the CRIB (clinical risk index for babies) score in prediction of neonatal mortality and morbidity.

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.

Birth weight and special educational needs: effects of an increase in the survival of very low birthweight infants in London.

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.

Preterm prelabour amniorrhexis: intrauterine infection and interval between membrane rupture and delivery.

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.

Intrathoracic extra-mediastinal cystic hygroma in infancy.

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.

Effect of fresh frozen plasma and gammaglobulin on humoral immunity in neonatal sepsis.

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 for preterm infants with severe respiratory failure.

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.

Neonatal meconium aspiration syndrome and respiratory morbidity during infancy.

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.

Arterial blood pressure and blood flow velocity in major cerebral and visceral arteries. II. Effects of colloid infusion.

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.