Jan H. Ruys

Aetiological rôle of cerebral blood-flow alterations in development and extension of peri-intraventricular haemorrhage

The aetiology and extension of peri‐intraventricular haemorrhage (PIVH) are thought to be related to cerebral blood‐flow alterations, and especially to increased cerebral blood‐flow and fluctuating velocity of blood‐flow. Using transcutaneous Doppler technique, the authors investigated cerebral blood‐flow in 60 infants with gestations of less than 34 weeks. Pulsatility index (PI) and area under the velocity curve (AUVC) of the anterior cerebral arteries (ACA) were used as qualitative measures of cerebral blood‐flow, and the coefficient of variation of PI and AUVC as indicators of fluctuations in blood‐flow velocity. A reasonable correlation was found between PI and AUVC and their coefficients of variation in the ACA. First onset of PIVH was related to fluctuating blood‐flow velocity, and extension of PIVH with both increased velocity (indicating increased blood‐flow) and fluctuating velocity. Increased cerebral blood‐flow and its fluctuating pattern were positively correlated with arterial carbon dioxide tension.

Incidence and prediction of periventricular-intraventricular hemorrhage in very preterm infants

During a prospective national survey of mortality and morbidity in infants born before 32 weeks gestation in the Netherlands in 1983, the incidence of periventricular-intraventricular hemorrhage (PIVH) was studied with ultrasound, in 484 of those infants. Stepwise logistic regression analyses were used to examine the predictive value of several maternal, prenatal and postnatal factors for the development of neonatal PIVH. PIVH was detected in 140 infants (28.9%); of these, 36 were grade I, 39 grade II, 22 grade III and 43 grade IV. The mortality rate increased from 3 to 84% with increasing severity of PIVH. Gestational age appeared to be the strongest predictive factor for both incidence and severity of PIVH, followed by idiopathic respiratory distress syndrome (IRDS), prolonged rupture of membranes and birth weight. Of the maternal and prenatal factors studied, only prolonged rupture of membranes (greater than 24 hours) and preeclampsia appeared to influence the risk of developing PIVH. Both were associated with a 50% reduction in the incidence of PIVH. None of the intrapartum factors studied showed a significant association with subsequent development of PIVH. Development of IRDS appeared to result in a twofold increase in the incidence of PIVH.

Is it correct to correct? Developmental milestones in 555 "normal" preterm infants compared with term infants.

To determine whether correction for preterm birth should be applied during developmental assessment, we conducted a prospective national survey of very premature infants (born at less than 32 weeks of gestation); neurodevelopment in the first 2 years was studied with the Dutch child health care developmental assessment. In 555 preterm children who had no evidence of handicap at 2 years of age, the age at which developmental milestones were reached was established. The results were compared with the results of the same assessment in Dutch children born at term. During the first year, the development of the very premature children equaled the development of normal children when full correction was applied. At 2 years of age, development was equal to or better than normal childrens development without correction. We conclude that full correction for prematurity should be applied in the first year to avoid overreferral for developmental stimulation, whereas at 2 years of age correction is not necessary.

CEREBRAL BLOOD-FLOW VELOCITY DURING THE FIRST WEEK OF LIFE OF PRETERM INFANTS AND NEURODEVELOPMENT AT TWO YEARS

Disturbances in perinatal cerebral perfusion appear to be associated with unfavourable neurodevelopmental outcome. Using transcutaneous Doppler technique, the authors investigated cerebral blood‐flow velocity patterns in the anterior cerebral artery (ACA) of an intensive care‐unit population of preterm infants during the first week of life. The results were correlated with neurodevelopmental outcome at two years of age. Children with major disability at two years of age had significantly higher pulsatility index (PI) values, mainly increased peak systolic flow velocity (PSFV), compared with children with normal or more favourable outcome. End diastolic flow velocity and area under the velocity curve values of the ACA did not differ between the groups, indicating that cerebrovascular resistance and cerebral blood‐flow were not different. It is thought that the higher PI and PSFV values were caused by increased compliance of the vascular bed supplied by the ACA, possibly induced by congestion and oedema of the periventricular white‐matter due to ischaemic lesions, which also cause periventricular leukomalacia.

Sudden infant death syndrome in child care settings in the Netherlands.

Background: In the Netherlands, there is a very low incidence of sudden infant death syndrome (SIDS) due to effective preventive campaigns. Methods: During the period September 1996 to August 2002, nationwide 161 deaths from SIDS (about 85% of all cases of SIDS during that time) were investigated by the Cot Death Committee of the Dutch Paediatric Association. Results and Discussion: Over 10% of cases of SIDS took place during some type of child care. From a national survey carried out in 2000/01 information was available on the child care attendance of 2000 Dutch infants aged 3–6 months. Based on the hours usually spent in child care by these infants, the number of similarly aged infants that died from SIDS while attending child care was 4.2 times higher than expected. Remarkably, the prevalence of known risk factors for SIDS, such as sleeping position and parental smoking, was favourable in the SIDS cases in child care settings. The adherence of child care facilities to the safe sleeping recommendations is high in the Netherlands, and no explanation as to why child care settings may be associated with an increased risk of SIDS is apparent. The possibility of other explanations, such as stress and change in routine care, is hypothesised.

Does Caffeine Affect Cerebral Blood Flow in the Preterm Infant

ABSTRACT. Caffeine, used for treatment of idiopathic apnea in preterm infants, may have a vasoconstrictive effect on cerebral vessels. The ensuing reduction in cerebral blood flow may play a role in the pathogenesis of ischemic brain damage. In 25 preterm infants possible changes in cerebral blood flow due to caffeine administration were assessed using Doppler ultrasound. During caffeine treatment PaCO2 was reduced. However, no changes were found in cerebral blood flow velocity suggesting absence of major changes in cerebrovascular resistance and actual cerebral blood flow following caffeine medication.

SERUM CK‐BB ACTIVITY IN THE PRETERM INFANT AND OUTCOME AT TWO AND FOUR YEARS OF AGE

The relationship between serum creatine kinase brain‐specific isoenzyme (CK‐BB) activity immediately after birth and neurodevelopmental outcome at two and four years corrected age was studied prospectively in 45 preterm infants (< 34 weeks gestation). Nine infants died during the neonatal period and one was lost to follow‐up. Of the 35 children available for follow‐up, seven had motor disabilities: four severe diplegia, two mild to moderate diplegia and one hemiplegia. No relationship existed between these motor disabilities and serum CK‐BB activity after birth. There seemed to be a relationship between increased serum CK‐BB after birth and low scores on the Bayley Scales of Mental Development, but this did not reach statistical significance. At the age of four years, four of the five survivors with high serum CK‐BB activity after birth (> 25U/L) needed special schooling because of mental retardation. Increased serum CK‐BB activity after birth may be associated with delayed mental development, but further study is needed, especially of asphyxiated infants.

PLACE OF BIRTH AND MORTALITY IN VERY PRETERM AND VERY LOW BIRTHWEIGHT (VLBW) INFNATS

The national collaborative survey on very preterm (<32 weeks) and/or VLBW (<1500 g) infants liveborn in The Netherlands in 1983, collected perinatal data on 1338 study infants born in 138 hospitals. We analysed the relation between place of birth and mortality, adjuting for a varying number of risk factors. All infants were assigned to 3 levels of care according to hospital of birth: Level 3: (university) hospitals, (n=8) Level 2: (regional) hospitals, limited neonatal facilities (N=19) Level 1: hospitals with no or little neonatal facilities (n=111). Logistic regression analysis with 4 perinatal factors as potential confounders (gestational age, birthweight, sex, multiple birth) showed a higher mortality risk for infants born outside the tertiary centers. Inclusion of 22 relevant perinatal factors (e.g. maternal disease, fetal position, multiple birth) increased the odds ratio further. Contrary to the current belief, the higher mortality risk in level 1 and 2 is even clearer if more differences in perinatal risk factors are taken into account.

Factor VIII-Related Antigen Assay in Capillary Samples

Factor VIII-related antigen was assayed in adults in venous citrated samples and in samples taken with heparinized and plain capillaries blown out in citrate. The three sampling methods gave nearly identical results in a wide range of values. Two of the sampling methods were used in newborns and again the results showed excellent correlation.

Incidence and prediction of patent ductus arteriosus (PDA) in a cohort of 1307 preterm infants

The aim of this study was to determine the incidence and predictive factors of PDA in a cohort of 1307 infants of less than 32 weeks gestation and/or birth weight below 1500 gms, representing 96% of these infants born within 1 year in the Netherlands.Symptomatic PDA was diagnosed (by clinical, radiological and ultrasound criteria) in 251 infants (19.2%).Using stepwise logistic regression analysis, it appeared that, among 9 perinatal factors tested, gestational age was the most predictive factor for both the occurrence and severity of PDA, followed by idiopathic respiratory distress syndrome.Furthermore, we found that infants with PDA had significantly more apnea and developed more bronchopulmonary dysplasia than infants without PDA.We conclude that onset and severity of PDA are especially determined by gestational age.