Increasing rates of cerebral palsy across the severity spectrum in north-east England 1964-1993. The North of England Collaborative Cerebral Palsy Survey.

OBJECTIVES: To report epidemiological trends in cerebral palsy including analyses by severity. DESIGN: Descriptive longitudinal study in north-east England. Every child with suspected cerebral palsy was examined by a developmental paediatrician to confirm the diagnosis. Severity of impact of disability was derived from a parent completed questionnaire already developed and validated for this purpose. SUBJECTS: All children with cerebral palsy, not associated with any known postneonatal insult, born 1964-1993 to mothers resident at the time of birth in the study area. MAIN OUTCOME MEASURES: Cerebral palsy rates by year, birth weight, and severity. Severity of 30% and above defines the more reliably ascertained cases; children who died before assessment at around 6 years of age are included in the most severe group (70% and above). RESULTS: 584 cases of cerebral palsy were ascertained, yielding a rate that rose from 1.68 per 1000 neonatal survivors during 1964-1968 to 2.45 during 1989-1993 (rise = 0.77; 95% confidence interval 0.2-1.3). For the more reliably ascertained cases there was a twofold increase in rate from 0.98 to 1.96 (rise = 0.98; 95% confidence interval 0.5-1.4). By birth weight, increases in rates were from 29.8 to 74.2 per 1000 neonatal survivors < 1500 g and from 3.9 to 11.5 for those 1500-2499 g. Newborns < 2500 g now contribute one half of all cases of cerebral palsy and just over half of the most severe cases, whereas in the first decade of this study they contributed one third of all cases and only one sixth of the most severe (chi(2) and chi(2) for trend p < 0.001). CONCLUSIONS: The rate of cerebral palsy has risen in spite of falling perinatal and neonatal mortality rates, a rise that is even more pronounced when the mildest and least reliably ascertained are excluded. The effect of modern care seems to be that many babies < 2500 g who would have died in the perinatal period now survive with severe cerebral palsy. A global measure of severity should be included in registers of cerebral palsy to determine a minimum threshold for international comparisons of rates, and to monitor changes in the distribution of severity.

Renal processing of glucose in well and sick neonates.

AIMS: To determine the extent of renal processing of glucose in sick and well neonates. METHODS: Glomerular filtration rate (GFR) and the renal processing of glucose, sodium, and water were measured using prolonged inulin infusion in 47 infants of 26-40 weeks of gestation, aged 1-13 days. RESULTS: GFR rose by 15% after ventilatory support was withdrawn, and was unaffected by clinical instability. Fractional glucose excretion was low in the stable unventilated babies except at very high filtered loads, but rose in one unstable, unventilated baby. It was higher in ventilated babies, and remained high for at least six days after ventilation. For water and sodium, net differences between intake and urine excretion were not affected by ventilation, clinical stability, or glycosuria. CONCLUSIONS: A combination of a low GFR and a high fluid intake, urine flow, and urine concentrating capacity, makes neonates very unlikely to develop an osmotic diuresis due to glycosuria while they have a blood glucose below 12 mmol/l, despite assertions to the contrary.

Haemodynamic effects of altering arterial oxygen saturation in preterm infants with respiratory failure.

AIMS: To examine the haemodynamic effects of brief alteration in arterial oxygenation in preterm infants with respiratory failure. METHODS: Eighteen preterm infants with respiratory failure, aged 9-76 hours, underwent detailed Doppler echocardiographic assessment at 86%, 96%, and 100% SaO2, achieved by altering the FIO2. Sixteen were receiving intermittent positive pressure ventilation, median FIO2 0.45 (0.20-0.65), median mean airway pressure 12 cm H2O (0-20). SaO2 was stable for 15 minutes at each stage. Four parameters of pulmonary arterial pressure were measured: peak velocity of tricuspid regurgitation and peak velocity of left to right ductal flow, TPV:RVET ratio and PEP:RVET ratio, measured at the pulmonary valve, along with flow velocity integrals at the aortic and pulmonary valves, and systemic arterial pressure. Ductal size was graded into closed, small, moderate, large with imaging, pulsed and continuous wave Doppler. RESULTS: Between 86% and 96% SaO2, there were no consistent changes, but in three of the 12 with a patent ductus arteriosus (PDA) there was ductal constriction, with complete closure in one. Between 96% and 100% SaO2, peak ductal flow velocity rose significantly in four of eight with a PDA. Ductal constriction occurred in four infants; in three this was associated with a significant fall in aortic flow integral and a rise in aortic pressure (4-6 mm Hg). Overall, 11 infants went from 86% to 100% SaO2 and pulmonary arterial pressure fell significantly in seven. CONCLUSION: A brief rise in SaO2 within the range maintained by most neonatal units can cause significant ductal constriction. The fall in pulmonary arterial pressure with 100% SaO2 seen in most infants was associated with a fall in pulmonary blood flow (or no change), rather than a rise, indicating that the dominant haemodynamic effect was ductal constriction rather than pulmonary vasodilation.

Bias due to incomplete follow up in a cohort study.

AIM: To investigate the bias introduced by incomplete follow up in a cohort study of ocular outcome after premature birth. METHODS: A geographically defined cohort of children born before 32 weeks' gestation was prospectively recruited at birth to study the ocular outcome at 2 years. On the basis of attendance at 2 years, the children's families were allocated to one of three groups: group 1 attended for follow up, group 2 were difficult to trace, and group 3 were very reluctant for assessment. All children were examined by a single ophthalmologist, masked to these groupings. RESULTS: 558 children (98.8% of study group) were examined, of whom 505 were in group 1, 20 in group 2, and 33 in group 3. The groups which were more difficult to study (groups 2 and 3) showed a significantly higher prevalence of ocular abnormalities, including strabismus (p=0. 02) and cicatricial retinopathy of prematurity (p=0.002) compared with those attending for follow up. Further, not all of these cases could have been identified by review of the children's previous records. Ocular abnormalities would be underestimated by 16% (11.3% in group 1 compared with 13.4% in the total cohort, p=0.77). CONCLUSIONS: This study suggests that the prevalence of abnormalities would be underestimated by incomplete follow up, as those subjects who were most difficult to obtain for study had a significantly higher prevalence of abnormalities.

Neonatal vitamin K administration and childhood cancer in the north of England: retrospective case-control study.

OBJECTIVE: To explore the possible association between intramuscular vitamin K given to neonates and the subsequent development of childhood cancer. DESIGN: Retrospective case-control study on the basis of hospital records. SETTING: The former Northern Health region of England. SUBJECTS: 685 children who were born and lived in the region and who developed cancer before their 15th birthday, and 3442 controls also born between 1960 and 1991 and matched only for date and hospital of birth. The notes of a further 701 index cases were untraceable. MAIN EXPOSURE MEASURE: Administration of intramuscular vitamin K versus no exposure to vitamin K. RESULTS: There was no association between the administration of vitamin K and the development of all childhood cancers (unadjusted odds ratio 0.89; 95% confidence interval 0.69 to 1.15) or for all acute lymphoblastic leukaemia (1.20; 0.75 to 1.92), but there was a raised odds ratio for acute lymphoblastic leukaemia developing 1-6 years after birth (1.79; 1.02 to 3.15). No such association was seen in a separate cohort-based study not dependent on case note retrieval in which the rates of acute lymphoblastic leukaemia in children born in hospital units where all babies received vitamin K were compared with those born in units where less than a third received prophylaxis. CONCLUSIONS: It is not possible, on the basis of currently published evidence, to refute the suggestion that neonatal intramuscular vitamin K administration increases the risk of early childhood leukaemia. Any association may have been masked in earlier studies that did not use controls matched for time and locality by other unidentified factors affecting the spatiotemporal variations in incidence of leukaemia.

Selection biases invalidate current low birthweight weight-for-gestation standards. The Northern Neonatal Network.

OBJECTIVE: To obtain unbiased estimates of the variation of birthweight with gestation in infants born before 32 weeks of gestation. SETTING: The former Northern Regional Health Authority. DESIGN: Information on birthweight was collected during a collaborative study of every registered and unregistered birth at 22 to 31 weeks of gestation in the region in 1983 and 1990 to 1991. These birthweights were then related to computer-generated Tyneside norms for all registered births at 28 to 42 weeks of gestation between 1984 and 1991. Some local information was also collected on fetal weight after termination of pregnancy on social grounds at 16 to 21 weeks of gestation. RESULTS: Weight centiles constructed after excluding infants with a gross, externally visible, malformation and those dying before the onset of labour suggest that previously published European standards have overestimated birthweight in infants < 28 weeks of gestation, some low centiles being 30% in error. Female and first-born infants weighed 4% less than their male and later-born counterparts at all gestations studied. A single correction factor can therefore be used to correct for sex and parity, eliminating the need for separate centile graphs. Twin pregnancy was associated with a 10% reduction in mean birthweight in pregnancies lasting < 37 weeks, and this difference increased progressively in pregnancies lasting longer than this. CONCLUSION: The small number of low birthweight infants in previous datasets and the selective exclusion of all nonregistered births have made previous second trimester weight-for-gestation norms unreliable.

Estimation of pulmonary arterial pressure in the newborn: study of the repeatability of four Doppler echocardiographic techniques.

Despite the increasing use of Doppler echocardiographic (DE) techniques to determine pulmonary arterial pressure in the neonate undergoing intensive care, there have been no studies comparing their repeatability in this population. Our objective was to compare the repeatability of four such techniques in neonates. The study was conducted in two regional neonatal units serving the North East of England. Group A (repeatability between observers): Two experienced observers performed detailed DE examinations, one directly after the other. Group B (within observer repeatability/temporal variability): One observer performed two examinations 1 hour apart. Group A comprised 15 preterm babies (26-36 weeks' gestation, 975-2915 g), most with mild respiratory failure; 4 healthy term babies; and 7 with congenital heart disease, in whom tricuspid regurgitation (TR) only was measured. Their ages were 18 hours to 12 days. Group B comprised 11 babies aged 12-64 hours with moderate to severe respiratory failure; 10 were preterm (26-36 weeks, 785-2800 g). We recorded four measurements: (1) Peak velocity of TR in m/s; (2) peak left-to-right ductal flow velocity (PDAmax in m/s); (3) TPV/RVET ratio; and (4) PEP/RVET ratio, where TPV = time to peak velocity at the pulmonary valve, PEP = right ventricular preejection period, and RVET = right ventricular ejection time. The Bland-Altman analysis was used to produce the coefficient of repeatability (CR: 95% confidence limits of repeatability), also expressed as a repeatability index (CR/mean value) and as a number of "confidence steps"-a measure of sensitivity of the technique to hemodynamic change (range of values within the population/CR). Between-observer and within-observer repeatabilities were similar. Within-observer CR and index (%) results were for TR +/- 0.26 m/s (9%); for PDAmax, +/- 0.48 m/s (39%); TPV/RVET 0.1:1.0 (34%), PEP/RVET 0.12:1.00 (36%). TR and PDAmax had the largest number of confidence steps in the expected range of values (TR 8.5; PDA max 6.5; TPV/RVET 3.2; PEP/RVET 3.2). The most repeatable technique was TR, but PDAmax would also be useful for a serial study owing to the potential for large change. Systolic time interval ratios were less repeatable and likely to be less sensitive indicators of hemodynamic change.

Haemodynamic features at presentation in persistent pulmonary hypertension of the newborn and outcome.

Thirty four newborns presenting with persistent hypoxaemia in the first three days of life underwent detailed haemodynamic assessment using Doppler echocardiography, including measurements of pulmonary arterial pressure (PAP), left ventricular (LV) function, and left ventricular output (LVO). Results were compared with values from 51 healthy babies, and those of survivors were compared with non-survivors. Four of the 34 babies were excluded from this analysis because one was found to have transposed great arteries, one had a large left-to-right shunt with no evidence of persistent pulmonary hypertension, and two had diffuse skeletal myopathy. Tricuspid regurgitation was present in 70%, permitting systolic PAP estimation. The pulmonary:systemic arterial pressure ratio range was 0.7:1 to 1.83:1 (mean 1.02:1). A patent duct was present in 83%, and flow patterns indicated PAP approaching, or above, systemic pressure in all. Systolic time interval ratio TPV/RVET (time to peak velocity at the pulmonary valve/right ventricular ejection time) was mostly (65%) in the normal range, and did not correlate with other PAP measurements. LV function was below the 10th centile in only 11%, but values for LVO lay below the 10th centile in 41%, and for left ventricular stroke volume index (LSVI) in 66%. Results of 18 survivors were compared with 10 non-survivors (excluding two premature babies who died early with pulmonary interstitial emphysema). There were no significant differences for any parameter of PAP or LV function, but LVO and LSVI were significantly lower in non-survivors: LVO survivors (mean (SD)), 205 (57), non-survivors 138 (63) ml/kg/minute (P < 0.01); LSVI survivors, 1.29 (0.51), non-survivors 0.86 (0.31) ml/kg (P < 0.05). All four babies with LVO < 100 ml/kg/minute died, and 6/7 babies with LSVI < 1 ml/kg died. Detailed echocardiographic evaluation shows that the haemodynamic features of persistent pulmonary hypertension are diverse and that clinical diagnosis can be incorrect. Low LV output and stroke volume, usually with normal LV function, were the only Doppler echocardiographic parameters to predict subsequent death. This correlation with outcome requires further prospective evaluation.

Limb reduction defects in the northern region of England 1985-92.

STUDY OBJECTIVE: To test the hypothesis that children born to mothers living near the sea are at increased risk of limb reduction defects. DESIGN: Descriptive data analysis. SETTING: The northern health region of England. PATIENTS: All children born between 1 January 1985 and 31 December 1992 in the northern region of England with isolated limb reduction defects. MAIN RESULTS: The birth prevalence of isolated limb reduction defects was not affected by the distance the mother lived from the sea. There was some evidence of space-time clustering, but there was no evidence of statistically significant variation in the occurrence of the condition with sex, time of birth (monthly or yearly), or county of birth. CONCLUSIONS: There is no evidence that children born to mothers living near the sea are at increased risk of limb reduction defects.

Pulmonary and systemic arterial pressure in hyaline membrane disease.

Systolic pulmonary arterial pressure was determined serially over the first 10 days of life in 33 babies with hyaline membrane disease by measuring the peak velocity of pansystolic tricuspid valve regurgitation, using Doppler ultrasound, and applying the Bernoulli equation. Results are presented in age groups 0-12, 13-36, 37-72, and 73-96 hours respectively. The incidence of tricuspid valve regurgitation was 92, 97, 80, and 64% (falling to 35% by day 10) compared with 53, 50, 31, and 0% in 17 healthy premature infants. In comparing healthy babies with those with hyaline membrane disease, no allowance was made for right atrial pressure. The derived 'right ventricle to right atrial (RV-RA) pressure difference', was expressed as a ratio of systemic arterial (systolic) pressure. Over the first three days, this ratio fell much faster in the healthy babies. Values were 0.78:1, 0.77:1, and 0.72:1 in babies with hyaline membrane disease and 0.87:1, 0.53:1, and 0.44:1 in healthy babies. Ductal patency was prolonged in babies with hyaline membrane disease (75% on day 4 compared with 6% in healthy babies). The incidence of bidirectional ductal flow, indicating balanced pulmonary and systemic arterial pressures, was 79, 53, 30, and 20%, and in healthy babies was 41% at 0-12 hours and zero thereafter. Pulmonary arterial pressure was then calculated by adding a right atrial pressure estimate of 5 mm Hg to the RV-RA difference when the babies were ventilated. Babies of lower gestation had lower values. The pulmonary: systemic arterial pressure ratio showed considerable temporal variability, but fell with age and was raised by high mean airway pressure and pneumothorax (through a reduction in systemic pressure), and less noticeably by carbon dioxide tension. It did not correlate significantly with other indices of disease severity. Hyaline membrane disease is associated with delayed postnatal circulatory adaptation characterized by pulmonary hypertension, systemic hypotension, and prolonged ductal patency.

Central venous pressure in the ventilated neonate.

As there is no other measurement of right ventricular preload, central venous pressure (CVP) measurement provides unique and important haemodynamic information. CVP is not measured routinely in neonatology and there is a shortage of data in the ventilated neonate. CVP was measured in 62 ventilated neonates. Thirteen had respiratory disorders (28-42 weeks' gestation, birth weight 860-4390 g) and 49 had congenital heart disease (birth weight 1600-4500 g, age 0.5-30 days). Data from other case reports are also presented. In the babies with respiratory distress, a value of zero was associated with clinical evidence of hypovolaemia and negative values, common in the unventilated neonate, did not occur in those who were ventilated. Values over 7 mm Hg were found in babies with evidence of myocardial dysfunction or persistent fetal circulation but were also found with transmitted high intrathoracic pressure, such as with pneumothorax. In the babies with congenital heart disease, values mostly lay between 4 and 8 mm Hg. Values outside this range, particularly above 8 mm Hg, were usually associated with profound metabolic acidosis, suggesting circulatory failure. While the main use of CVP measurement is in trend analysis, this report suggests that single measurements can be of value, though correct interpretation will depend on the context in which they are made.

How good is ultrasound in the detection and evaluation of anterior abdominal wall defects?

The ability of routine obstetric ultrasound to detect and accurately describe fetuses with anterior abdominal wall defects has been examined in an unselected population using data from a regional abnormality survey. Examination between 16 and 22 weeks gestation detected 60% of defects with a false positive rate of 5.3%. Fetuses with gastroschisis were incorrectly assigned as exomphalos in 14.7% of cases recognized before 22 weeks gestation. The diagnosis, including description of associated detectable anomalies, was completely accurate in 71.6% of cases. Some of the problems of diagnostic accuracy need to be considered when counselling couples with a fetal anomaly. Cross-referral between obstetric ultrasound units should be encouraged to improve diagnostic accuracy. These results form the basis for audit of obstetric ultrasound in the diagnosis of fetal abnormality within a geographically defined population.

Respiratory illness in children: do deprived children have worse coughs?

Parents of a stratified random sample of 234 children from 21 general practices in North East England were interviewed at home. All these children had been reported in a postal questionnaire as having had a cough between six and ten weeks before the interview. Interviews covered social characteristics of the family, the severity of the child's cough and the reactions of the parents to hypothetical sets of symptoms. The parents of children in materially deprived circumstances appeared to report worse coughs than other parents. We confirmed this finding by constructing a scale of perceived cough severity. However, we found no evidence that the inequality was due to exaggeration of the severity of the cough by materially deprived parents. Our conclusion that materially deprived children suffer worse respiratory illness is the more important because previous evidence suggests that the after-effects persist into adulthood.

Hypoplastic left heart syndrome: more potential transplant recipients than suitable donors.

Neonatal cardiac transplantation offers the prospect of survival for babies with hypoplastic left heart syndrome--but only if suitable donors are available. In a retrospective survey in the Northern health region of England and Wales, the likely need for neonatal cardiac transplantation far outweighed the potential availability of donors. Over 8 years (1983-90) hypoplastic left heart syndrome was identified in 38 newborn babies and in 9 fetuses in utero. Of 41 live births (including 3 diagnosed prenatally) 31 would have been candidates for a cardiac transplant, but only 4 suitable donors could be identified (3 with anencephaly born alive during the same period and 1 who died between 1979 and 1986 after a head injury). Analysis of all infant deaths in 1987-89 revealed only 3 potential donors from 426 deaths in the 3 years. Although more widespread antenatal diagnosis may lead to fewer liveborn babies with hypoplastic left heart syndrome, these findings indicate that an alternative source of donors needs to be identified before neonatal cardiac transplantation can be widely used in the treatment of this disorder.

Non-invasive assessment of pulmonary arterial pressure in healthy neonates.

Doppler echocardiograms were carried out on 51 healthy babies three times during the first 72 hours of life to estimate pulmonary arterial systolic pressure by measuring regurgitant tricuspid jet velocity and applying the Bernoulli equation. Tricuspid regurgitation was detected at some stage in all preterm babies and most of those born at full term. Pulmonary arterial pressure could be measured from peak regurgitant velocity in babies with pansystolic regurgitation. The incidence of pansystolic regurgitation among 34 term babies at 0-12, 13-36, and 32-72 hours of age was 22, 27, and 19%, and in 17 preterm babies (within the same age groups) was 53, 50, and 31%, respectively. Estimates of pulmonary artery pressure in the term babies were in accord with known catheter values. Pressure fell rapidly during the first day in all 51 babies. The ratio of pulmonary:systemic arterial pressure was comparable between the two groups throughout. Ductal flow patterns mirrored the fall in this ratio with age--bidirectional flow was associated with a ratio of between 0.88:1 and 1.22:1 and high velocity left to right flow with a ratio of between 0.49:1 and 0.66:1. Both these techniques are noninvasive ways of assessing neonatal pulmonary arterial pressure.

Neurodevelopmental outcome of transient neonatal intracerebral echodensities.

The later neurodevelopmental progress of 15 babies who had neonatal periventricular echodensities or flares in the absence of any intraventricular bleeding or subsequent cystic degeneration was studied. At follow up four infants had neurological abnormalities, including spastic diplegia (n = 2). These findings suggest that transient flares may represent mild periventricular leucomalacia with consequent mild neurological dysfunction.