Infantile hydrocephalus in preterm, low-birth-weight infants—a nationwide Swedish cohort study 1979–1988

All Swedish infants with shunt-treated infantile hydrocephalus, born during the period 1979–88 at 34 weeks gestational age and of low birth weight, were studied. Ninety-six infants were born before 32 weeks and 50 at 32–34 weeks. The mean gestational age in the very preterm group gradually decreased from 29.5 to 27.3 weeks. The mean live birth prevalence was 15.9 per 1000 very preterm infants, and 5.1 per 1000 moderately preterm infants. No significant secular prevalence trends were found. The perinatal mortality decreased successively. The slowly decreasing trend in moderately preterm infants may imply better outcome in survivors. The slightly increasing trend in very preterm infants could be explained by more survivors in the low gestational age group. The aetiology was considered perinatal in 94% of the very preterm group and in 56% of the moderately preterm group; prenatal in 1% and 32% of infants, respectively. Additional neuropimairments were present in 82% of infants, cerebral palsy being the commonest (74%).     

Measurement of transepidermal water loss in Tanzanian cot-nursed neonates and its relation to postnatal weight loss

In healthy cot-nursed Tanzanian neonates ( n = 92, gestation 26–42 weeks) measurements of transepidermal water loss (TEWL) and weight change were performed during the first 24 h after birth at an average ambient humidity of 70% and an environmental temperature of 32°C. Urine production on day 1 (ml/kg per 24h) was documented for a subgroup of 13 preterm and 8 term infants. In a limited group of preterm infants ( n = 5) TEWL measurements, weight and 24 h urine volume measurements were repeated daily for 7 days. Maximum weight loss was determined in 7 preterm (gestational age 30–36 weeks) and 6 term infants. TEWL was estimated by measuring the evaporation rate at three sites of the body using the water vapour pressure gradient method. On day 1, TEWL was highest in the most preterm infants, whereas TEWL and urine production were higher in large for gestational age infants as compared to appropriate for gestational age (AGA) infants of the same gestational age (31–36 weeks). For the whole group, weight loss on day 1 was correlated with TEWL ( r = 0.49, p <0.05). At follow-up TEWL in preterm infants remained almost constant during the first 4 days and decreased after the fourth day, at which time weight gain commenced. Preterm AGA infants (gestational age 24–37 weeks) showed a mean postnatal weight loss of 4.4% of the birth weight, while in term infants this loss was only 2.6%. A reduced postnatal weight loss as compared to Caucasian infants may be explained by a lower water loss during the first days after birth, through both skin evaporation and urine excretion.     

Normal Pattern of the Cerebral Function Monitor Trace in Term and Preterm Neonates

ABSTRACT. Cerebral Function Monitor (CFM) recordings were performed on 10 term and 19 preterm healthy infants. Term infants were monitored once, while preterm infants were followed serially. Forty-six recordings were made on 7, 14, 16 and 9 occasions in the age groups 30–31, 32–33, 34–35 and 36–37 weeks. All infants were examined clinically at 18 months of age and found healthy. By drawing weighted lines derived from the lower and upper limits of the CFM traces, mean values of minimum and maximum cerebral activity were calculated for the different age groups. In the term infants different CFM traces were identified corresponding to quiet sleep and active sleep. In the preterm infants a similar cyclic variability of the CFM trace was noted. A gradual increase in the minimum cerebral activity was found with increasing gestational age, resulting in a gradual narrowing of the trace.     

Free-radical-induced lipid peroxidation during the early neonatal period

The effect of gestational age on postnatal free-radical-mediated lipid peroxidation was studied in 19 term (gestational age 37–42 weeks) and 21 healthy preterm (gestational age 31–36 weeks) infants by measurement of expired ethane and pentane during the first 7 days of life. Ethane (11.9 versus 5.7 pmol/kg/min; p = 0.0001) and pentane (11.4 versus 7.5 pmol/kg/min; p = 0.01) were significantly higher in preterm than in term infants. Correlations were found between gestational age and ethane ( r = 0.60, p = 0.0001) for days 1–7 and pentane ( r = 0.54, p = 0.0003) for days 3–7; and between birth weight and ethane ( r = 0.58, p = 0.0001) and pentane (r = 0.55, p = 0.0003). These results indicate that during the postnatal period, immaturity is a major factor determining the rate of free-radial-mediated lipid peroxidation.     

POSTNATAL DEVELOPMENT OF RENAL HYDROGEN ION EXCRETION CAPACITY IN RELATION TO AGE AND PROTEIN INTAKE

ABSTRACT. Svenningsen, N. W. and Lindquist, B. (Department of Paediatrics, University Hospital, Lund, Sweden). Postnatal development of renal hydrogen ion excretion capacity in relation to age and protein intake. Acta Paediatr Scand, 63: 721, 1974.—The cumulative and maximum renal hydrogen ion excretion capacity after induced acidosis has been studied in six term and twenty preterm infants at 1–3 and 44 weeks of postnatal age corresponding to for preterm babies 34–36 and 37–39 and for term babies 41–43 and 44–46 weeks of gestational age. The maximum net hydrogen ion (H⁺_NAE) excretion capacity is lower in preterm than in term infants at 1–3 weeks of postnatal life. However, when approaching full gestation there is a considerable increase of the H+_NAE excretion capacity of pretem infants almost equal to that found in term infants at 1–3 weeks of age. High dietary protein intake lasting for in average two to three weeks in preterm infants does not change the maximum renal H⁺ excretion during induced acidosis, but significantly enhances the initial increment of excretion rate of titratable acid (H⁺_TA) in comparison to preterm infants fed low protein diets. The findings of the present investigation suggest that the development of renal hydrogen ion excretion capacity in preterm infants during the first weeks of life is related primarily to gestational age. This development may, however, to a certain degree respond to increased excretory needs imposed by dietary load.     

Low neonatal cerebral oxygen delivery is associated with brain injury in preterm infants

Neonatal cerebral oxygen delivery was estimated in 93 preterm infants (gestational age < 34 weeks) who survived the neonatal period. Of these, 26 had developed neurological handicap at follow-up 1.7–4.6 years later. Neonatal cerebral oxygen delivery was dependent on gestational age, and was also related to the degree of intra-uterine growth retardation, carbon dioxide tension, and blood glucose concentration. Lower oxygen delivery was observed in infants who developed germinal layer haemorrhage or periventricular leucomalacia compared with infants with normal brains. However, as no information on cerebral metabolic demand or oxygen extraction is available, it is unclear whether decreased oxygen delivery is a contributing factor to brain damage or whether it is a marker of existing injury.     

Brainstem size and function at term age in relation to later neurosensory disability in high-risk, preterm infants

The aim of this study was to measure brainstem size on magnetic resonance imaging (MRI) scans of high-risk, preterm infants, to assess brainstem function by brainstem auditory-evoked potentials (BAEP) and to determine the predictive value of these measures for the neurosensory outcome. A total of 51 preterm infants (gestational age <34 wk, birthweight <1500 g) underwent examinations at term age; neuromotor outcome and hearing were followed up until a corrected age of 18 mo. Fourteen (27%) infants had neurosensory disability. Those with a later neurosensory disability had a significantly smaller brain stem than those with a normal outcome. The preterm infants had significantly longer peak latency (L) V and interpeak latency (IPL) III–V than the full-term control infants. Most of the preterm infants with severe cerebral palsy or hearing loss had abnormal BAEP. Sensitivity of morphometric dimensions for predicting neurosensory disability was only 20–31%, but specificity was 97–100%. Abnormal L I and IPL III–V in BAEP predicted disability with a sensitivity of 93% and a specificity of 57–59%.
Conclusion: We conclude that adverse events during the perinatal period may lead to morpho-functional changes in the brain stem in high-risk, preterm infants, and it seems that functional changes are accurate in predicting neurosensory disability in such patients.     

Effects of positive and negative pressure ventilation on cerebral blood volume of newborn infants

The effects of intermittent positive airway and continuous negative extrathoracic pressure ventilation on cerebral blood volume in preterm infants were studied using near infrared spectroscopy. In 12 infants continuous negative extrathoracic pressure caused a median decrease in cerebral blood volume of 0.14ml/100ml brain (95% confidence intervals (CI) 0.035–0.280) compared with no respiratory support. Oxygenated and deoxygenated haemoglobin also decreased, implying increased venous drainage as the main effect. In 17 infants intermittent positive pressure ventilation also caused a median reduction in cerebral blood volume of 0.06 ml/100 ml brain (95% CI 0.010–0.115) compared with endotracheal positive airway pressure. Deoxygenated haemoglobin increased by 0.07 ml/100 ml brain (95% CI 0.010–0.100) while oxygenated haemoglobin decreased by O.lOml/lOOml brain (95% CI 0.005–0.175). The increase in deoxygenated haemoglobin implies decreased venous drainage and the decrease in oxygenated haemoglobin implies that other factors may also be significant. Heart rate, blood pressure and oxygen saturation were monitored continuously and remained stable.     

Cerebral and Abdominal Arterial Hemodynamics in Preterm Infants with Patent Ductus Arteriosus

Using Doppler echocardiography we evaluated the effect of ductal shunt flow on the cerebral and abdominal arterial blood flow in 25 preterm infants. Eligible for inclusion in this study were healthy preterm newborn infants. They were divided into two groups based on their gestational age: group A, 33-36 weeks (15 infants) and group B, 28–32 weeks (10 infants). Two-dimensional Doppler echocardiograms were obtained in each infant during the first 8 hours of life and repeated every 6–12 hours until no ductal shunt flow could be detected. Flow in the ductus arteriosus, the basilar artery and the coeliac artery were examined. Closure of the ductus arteriosus occurred significantly later(p< 0.05) in group B than in group A. Pulsatility indices of flow in the basilar and coeliac arteries were high when the ductus was patent, decreasing to a fixed level with closure. This study suggests that a shunt of the patent ductus arteriosus (PDA) adversely influences the cerebral and abdominal blood flow in preterm infants.     

Inflammation at birth and the insulin-like growth factor system in very preterm infants

BACKGROUND: Foetal inflammation is associated with an increased risk of brain damage in preterm infants whereas IGF-I is essential for cerebral development and exhibits anti-apoptotic properties. AIM: To assess levels of IGF-I and IGF binding proteins at very preterm birth and to evaluate their relationship with foetal pro-inflammation and cerebral damage. METHODS: Levels of IGF-I, IGF binding protein 3 (IGFBP-3), high- (hp) and low-phosphorylated (lp) IGFBP-1 in cord blood and neonatal blood at 72 h after delivery were analysed in relation to levels of cytokines and cerebral damage as detected by ultrasound in 74 inborn infants [mean gestational age (GA) 27.1 weeks]. Evaluation was performed separately according to birth weight for GA. RESULTS: In cord blood of infants appropriate for gestational age (AGA) higher levels of IL-6 and IL-8 were associated with lower IGF-I (r =-0.38, p = 0.008 and r =-0.36, p = 0.014). Higher levels of IL-6, IL-8 and TNF-alpha were associated with both higher levels of lpIGFBP-1 (r = 0.54, p < 0.001, r = 0.50, p < 0.001 and r = 0.13, p = 0.012, respectively) and hpIGFBP-1 (r = 0.55, p < 0.001, r = 0.45, p = 0.002 and r = 0.32, p = 0.026, respectively). Infants with intraventricular haemorrhage grade III (n = 5) had higher levels of lp/hpIGFBP-1 in cord blood (p = 0.001 and 0.002, respectively). CONCLUSION: Pro-inflammation at birth is associated with changes in the IGF-system. This may be of importance for development of brain damage in preterm infants.     

早产儿早期脑反应性与神经发育关系的研究

目的　研究早产儿早期脑对外界刺激的反应性与神经发育的关系 ,早期对早产儿进行脑功能的评价 ,为了解其神经发育水平、估价预后提供客观证据。方法　应用近红外光谱测定技术 ,对不同胎龄的早产儿进行脑氧合状态的监测 ,观察声刺激后脑反应性的变化 ;在纠正胎龄 4 0周时行新生儿神经行为评分 (NBNA) ,并进行神经发育随访 ,评价早产儿早期脑反应性与其后神经发育的关系。结果　本组早产儿生后对声刺激均显示出不同程度的反应 ,34周后的早产儿声刺激后最大反应值为 4 .1%± 1.4 % ,2 0例足月儿声刺激后最大反应值为 4 .2 %±1.4 % ,两者差异无显著性 ;小于 34w的早产儿声刺激后最大反应值为 3.1%± 1.4 % ,与足月儿相比差异有显著性(P <0 .0 5 )。有脑损伤早产儿声刺激后最大反应值为 2 .6 %± 1.8% ,无脑损伤早产儿声刺激后最大反应值为4 .4 %± 1.3% ,两者相比有统计学差异 (P <0 .0 5 )。纠正胎龄 4 0周的NBNA异常儿与正常儿比较 ,早期脑反应性有显著性差异 (P <0 .0 5 )。婴幼儿期随访 ,神经发育异常与正常儿比较 ,早期脑反应性也有显著性差异 (P <0 .0 5 )。结论　早产儿具备对声刺激后的脑反应性 ,成熟度越低 ,脑反应性越差。围产期脑损伤可影响脑的反应性。早期的脑反应性与神经发育水平有关。     

Influence of gestational age on nosologic CP characteristics in a high-risk population

The aim of this study is to investigate the interrelationship between gestational age (GA) and nosologic characteristics (type, distribution and severity) of cerebral palsy (CP) in a cohort of high-risk infants. One thousand ninety-nine consecutively neonatal intensive care unit-admitted high-risk infants (i.e., all infants with a GA less than 30 weeks and specified infants with GA ≥ 30 weeks with a complicated neonatal course and/or brain lesion) were prospectively assessed up to the corrected age of 2 years or more. In 177 (16%) of these infants, CP was diagnosed. Of these infants, 26 were extremely preterm infants (GA 23–27 weeks), 62 very preterm (28–31 weeks), 36 moderately preterm (32–36) and 53 term infants (GA ≥ 37 weeks). Spastic CP was significantly more present in the three preterm groups (77%, 90% and 72%, respectively) compared with the term ones (42%). At variance, dyskinetic CP was present in nearly half of the term group (47%) and remarkably less in all three preterm age groups (12%, 7% and 22%, respectively). Ataxic CP (7%) was of rare occurrence in all age groups. Distributive classification showed that bilateral spastic CP gradually dropped from 100% in the extremely preterm group down to 50% in the term infants. Inversely, unilateral spastic CP rises steeply with advancing GA. Severity of CP was significantly associated with birth year period in favour of mild CP. In high-risk neonates, dyskinetic CP increases steeply with increasing GA, whereas spastic CP decreases. Bilateral and unilateral involvements are gradually and oppositely changing with gestational age. It is tempting to explain the maturity-related association by gestational age-specific brain injuries.     

Intrauterine growth and gestational age in preterm infants with cerebral palsy

In a case-control study, gestational age and intrauterine growth of 191 preterm singleton infants 1971–1982 with cerebral palsy were compared to all preterm live-born singletons in Denmark in 1982 (N = 2203). The distribution of gestational age among preterm cases was slightly bimodal with maximum values at 29 and 32 weeks. The risk for cerebral palsy was highest in the infants with gestational age 28–30 weeks (OR = 5.6 (4.0 – 7.8), 95% confidence interval). Birth weight deviation, in the 34–36 weeks infants, expressed as the number of standard deviations from the mean birth weight for gestational age, was more negative in cases than in controls (P < 0.001). The frequency of small for gestational age (SGA) was 13% in cases and 9% in controls (OR = 1.5 (0.96 – 2.3), 95% confidence interval). The odds for cerebral palsy being SGA, was lower in 28–30 weeks (OR = 0.22 (0.06 – 0.86), 95% confidence interval), the same in 31–33 weeks (OR = 0.83 (0.35 – 2.0), 95% confidence interval) and higher in 34–36 weeks (OR = 5.2 (2.9 – 9.5), 95% confidence interval). In conclusion, preterm infants with cerebral palsy are born earlier than other preterm infants. Small for gestational age is associated with cerebral palsy in preterm infants only above 33 weeks.     

Plasma somatostatin and cholecystokinin levels in sick preterm infants during their first six weeks of life

Abstract The present study reports the levels of plasma somatostatin and cholecystokinin in 19 preterm infants with asphyxia [ n =10, GA (median; range) 26; 23–30 weeks] and respiratory distress syndrome ( n = 14, GA 27; 23–29 weeks) compared with preterm infants without any of these conditions (reference group, n = 59, GA 33; 25–36 weeks). In the reference group 37 infants received phototherapy and their peptide levels were compared with those not receiving phototherapy ( n = 22). Plasma somatostatin and cholecystokinin were analysed by specific radioimmunoassays on day 1, day 3–4 and at 6 weeks of life. Plasma somatostatin levels, but not cholecystokinin levels, of reference infants were inversely related to gestational age on day 1 and day 3–4. Asphyxiated infants and infants with respiratory distress syndrome had significantly higher somatostatin levels than reference infants on day 1 and day 3–4. These differences disappeared when the levels were adjusted for gestational age. Plasma cholecystokinin levels were not influenced by respiratory distress syndrome and asphyxia. Phototherapy did not affect plasma somatostatin and cholecystokinin levels.     

Respiratory distress syndrome in infants with impaired intrauterine growth

The recently introduced intrauterine growth curve, based on ultrasonically estimated foetal weights, was retrospectively applied to an inborn population of 883 infants bom before 33 gestational weeks at the University Hospital of Lund, during 1985–94. The estimation of birthweight deviation resulted in 630 (71.3%) infants with a birthweight appropriate for gestational age (AGA), 244 (27.6%) infants with a birthweight small for gestational age (SGA) and 9(1.1%) infants with a birthweight large for gestational age. Birthweight deviation was associated with an increased mortality [odds ratio (OR) adjusted for gestational age 1.29 per SD (12%) change in birthweight for gestational age, 95% CI: 1.10–1.50; p = 0.002]. At gestational age 25–28 weeks, SGA-infants had an increased incidence of respiratory distress syndrome (RDS) as compared to AGA-infants (OR adjusted for gestational age: 1.98,95% CI: 1.12–3.52; p = 0.019). At gestational age 29–32 weeks, SGA-infants had a lower incidence of RDS as compared to AGA-infants (OR adjusted for gestational age: OR 0.52,95% CI: 0.34–0.80; p = 0.003). After adjustment for confounding variables, infants born at gestational age 25–28 weeks from mothers with pre-eclampsia, appeared to be a high-risk group for RDS, whereas at the age of 29–32 gestational weeks, negative birthweight deviation had a protective effect against RDS. Antenatal corticosteroid administration appeared to have a less beneficial effect on mortality, RDS and cerebral haemorrhage in infants born SGA vs in those born AGA.     

VITAMIN E REQUIREMENTS OF PRETERM INFANTS

ABSTRACT. Differences between feeding practices in earlier investigations prompted the present study of iron and vitamin E supplementation in breast milk fed preterm infants. A new and highly sensitive technique for quantitation of alpha-tocopherol in serum was used. Studies on 34 infants with a birth weight below 2000 g or gestational age ≤35 weeks showed that supplementation with 16.5 mg tocopheryl acetate/day from 10 days of age resulted in a significantly higher haemoglobin concentration and lower reticulocyte count at 8–10 weeks than supplementation with 1.5 mg/day (p<0.05). Studies on 23 infants with a birth weight of 2000–2499 g revealed subnormal alpha-tocopherol levels in 2 of the infants given 1.5 mg tocopheryl acetate/day but there was no effect on the haemoglobin concentration at 8–10 weeks. There were no untoward effects of an early iron supplementation with 2–3 mg Fe⁺⁺ (as ferrous succinate)/kg/day. It is concluded that extra supplementation with vitamin E is advisable also in breast milk fed preterm infants. A low dosage iron supplementation from 3 weeks of age is safe.     

Intestinal permeability in relation to birth weight and gestational and postnatal age

OBJECTIVE: To determine the relation between intestinal permeability and birth weight, gestational age, postnatal age, and perinatal risk factors in neonates. STUDY DESIGN: Intestinal permeability was measured by the sugar absorption test within two days of birth and three to six days later in preterm and healthy term infants. In the sugar absorption test, the urinary lactulose/mannitol ratio is measured after oral ingestion of a solution (375 mosm) of lactulose and mannitol. RESULTS: A first sugar absorption test was performed in 116 preterm (26-36 weeks gestation) and 16 term infants. A second test was performed in 102 preterm and nine term infants. In the preterm infants, the lactulose/mannitol ratio was not related to gestational age (r = -0.09, p = 0.32) or birth weight (r = 0.07, p = 0.43). The median lactulose/mannitol ratio was higher if measured less than two days after birth than when measured three to six days later (0.427 and 0.182 respectively, p<0.001). The lactulose/mannitol ratio was higher in preterm infants than term infants if measured within the first 2 days of life (0.404 and 0.170 respectively, p < 0.001), but not different three to six days later (0.182 and 0.123 respectively, p = 0.08). In multiple regression analysis of perinatal risk factors, only umbilical arterial pH correlated with the lactulose/mannitol ratio in preterm infants less than 2 days of age (T = -1.98, p = 0.05). CONCLUSIONS: In preterm infants (26-36 weeks gestation), intestinal permeability is not related to gestational age or birth weight but is higher during the first 2 days of life than three to six days later. It is higher in preterm infants than in healthy term infants only if measured within two days of birth. This suggests rapid postnatal adaptation of the small intestine in preterm infants.     

影响早产儿脑损伤的相关因素分析

目的分析早产儿不同类型脑损伤的发生情况及影响因素。方法收集239例早产儿的临床资料及头颅磁共振检查结果,分析产前、产时、产后因素对早产儿脑损伤的影响。结果早产儿脑损伤的发生率为25.5%,其中出血性脑损伤占10.5%,缺血性脑损伤占10.5%,出血+缺血性脑损伤占4.6%。胎龄越小,出血性脑损伤及总脑损伤发生率越高(P0.01),缺血性脑损伤及出血+缺血性脑损伤的发生率与胎龄无关(P0.05)。出血性、缺血性及总脑损伤发生率均与出生体重无关(P0.05)。胎龄34周早产儿脑损伤的保护因素是经产(OR=0.292,95%CI:0.088~0.972)和剖宫产(OR=0.075,95%CI:0.015~0.368);胎龄≥34周早产儿脑损伤的保护因素是剖宫产(OR=0.296,95%CI:0.131~0.672),危险因素是严重感染(OR=8.176,95%CI:1.202~55.617)。结论在临床工作中,应尽量延长早产儿的胎龄、掌握剖宫产指征,积极有效地预防及治疗感染,以期预防或减少早产儿脑损伤的发生。     

Morphine pharmacokinetics in premature and mature newborn infants

The pharmacokinetics of a single dose of morphine was investigated in five term infants (gestational age 37–40 weeks) and eight preterm infants (gestational age 25–32 weeks). In the five term infants, median (range) volume of distribution at steady state (Vd_β) was 1758 (634–2700) ml/kg, plasma clearance (Cl) was 4.73 (1–75–6.61) ml/kg/min and terminal half-life (T1/2) was 224 (107–394) min. In the eight preterm infants, Vd_β was 2366 (1662–2876) ml/kg, Cl was 2.82 (1.88–6.60) ml/kg/min and T1/2 was 556 (248–834) min. No correlation was found between clearance and gestational age, but we found a significant negative correlation between T1/2 and gestational age. We conclude that there is considerable variation in the pharmacokinetic properties of morphine in both term and preterm newborn infants. Because of this variation, careful individual assessment of the clinical effect of therapy with morphine in newborn infants should be exercised.     

Loss of CO2 reactivity of cerebral blood flow is associated with severe brain damage in mechanically ventilated very low birth weight infants.

BACKGROUND: Early detection of pathophysiological factors associated with permanent and severe brain damage in preterm infants requiring intensive care is a major issue in neonatal neurology. The aim of this study was to investigate if an abnormal CO2 reactivity of cerebral blood flow in high risk very low birth weight infants is associated with severe brain injury demonstrated at autopsy or by neurodevelopment examination at 18 months. METHODS: The CO2 reactivity of cerebral blood flow (xenon-133) was measured in 18 mechanically ventilated, severely ill, very low birthweight infants (gestational age 26-32 weeks, birthweight: 630-1360 g) during the first 36 hours of life. Cerebral outcome was assessed on autopsy findings (n = 8) or at the age of 18 months using Bayley developmental scales (n = 10). RESULTS: Eight infants with normal development at 18 months (within mean +/- 2.5 SD of reference group) and two infants with normal cerebral autopsy findings had a median CO2 reactivity of 24.4%/kPa CO2 (interquartile range 14.7-41.2). Two infants with abnormal development (> 2.5 SD below mean) and six infants with hypoxic-ischaemic encephalopathy at autopsy has a median CO2 reactivity of 3.4%/kPa CO2 (interquartile range 8.0-11.7). CONCLUSION: In mechanically ventilated very low birthweight infants low CO2 reactivity of cerebral blood flow (below 10%/kPa CO2) during the first 36 hours of life was associated with poor neurodevelopmental outcome or hypoxic-ischaemic encephalopathy at autopsy. Loss of CO2 reactivity may play a role in the pathogenesis of hypoxic ischaemic encephalopathy. It is a candidate for predicting early severe brain damage in preterm infants requiring intensive care and for controlling the effect of early interventions.