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Computerized analysis of the neonatal EEG provides a measure of cerebral function in the very preterm infant. This method has enabled observation of the effects of inotropic infusions on cerebral function in 13 sick infants between 24 and 30 weeks gestation. Inotropes used included dopamine, dobutamine and nor-adrenaline, either singly or in combination as dictated by the clinicians. On commencement of inotropic therapy, no deterioration in EEG was seen and improvement was noted in only 3 of 18 occasions. Monitoring during a further 12 increases in inotropic therapy showed associated improvement in the EEG in only one of these occasions. However, on reduction of the inotropic treatment, which was no longer deemed clinically necessary, there was an associated improvement in EEG in 12 of 16 occasions monitored. The EEG improvement on reduction in inotropic therapy appeared to be related to the duration of use of inotropes and to tho duration of time normotension had been achieved. These results imply that withdrawal of inotropic therapy should perhaps be considered as soon as clinically feasible as this dolotorious effect of inotropic infusions on cerebral function may be related to enchanced cerebro-vascular sympatho-adrenal tone.

Prematurity remains a major cause of perinatal morbidity and mortality and in spite of considerable scientific inquiry over the years the cause, certainly of spontaneous preterm labour, remains uncertain. This mini-symposium re-explores some old information and presents novel and exciting concepts into the possible underlying pathology. The basic understanding of the mechanisms of normal labour seem a good starting point for establishing what might be happening when things go wrong. Certainly the onset of normal labour is an immensely complex matter involving cervix, uterus and the fetus itself and it is interesting to see how, with increasing knowledge, the interactions between all three components (there may be more!) are becoming increasingly comprehensible. Undoubtably one important cause of preterm labour is infection and the mechanisms by which this may induce labour are gradually being uncovered. It can be no coincidence that certain infections may influence the biochemical cascade which eventually leads to established labour. How to effectively interfere once the cascade has been activated remains a problem but at least improved understanding helps to target some obvious sites. For example merely treating the infection is unlikely to be often successful and the effective manipulation of the cascade itself is an important challenge. The obstetric management of preterm labour remains at a relatively unsophisticated level, but, as pointed out, well-designed protocols will be likely to optimise outcome. Certainly these cases should not be left in the hands of our most junior colleagues. The importance of attempting to delay labour to evaluate the fetal condition, give steroids to accelerate lung maturity and transfer the mother and her fetus to a suitable unit cannot be over-emphasised. Finally, the pivotal role of the neonatologist in improving perinatal survival in the preterm neonate must always be acknowledged. Advances in our understanding of neonatal physiology, the major technological developments and the appearance of artificial surfactant have all played an important part and so long as the neonatologist receives the baby in good condition prognosis for intact survival, even of the very preterm infant, is outstandingly good.

SUMMARY There appears to be no doubt that where there is supportive obstetric care and intensive neonatal care, the long-term outlook for the very preterm infant has improved dramatically since the 1950s. However, the rate of neurodevelopmental handicap in these children is still unacceptably high when compared with term infants. To improve their outlook, modifications of obstetric and neonatal care, particularly in relation to the prevention of hypoxic, traumatic and biochemical insults, must continue to be introduced and tested until more fundamental research determines the mechanisms underlying preterm labour, and makes more effective prevention and treatment of preterm labour possible. Those infants who have suffered IUGR, certainly when it has been severe, never achieve their full intellectual potential. It is already recognized that some of the associated problems of IUGR cause handicap. Intrapartum hypoxia/acidosis, neonatal hypothermia, hypoglycaemia, polycythaemia and hyperbilirubinaemia for example, should be identified and appropriate action taken to prevent their effects. Further research is required to determine what duration and character of IUGR alone influences intellectual development before intervention in these pregnancies can be investigated.

That death or major developmental handicap is associated with prematurity and low birth weight is well recognized. The importance of other perinatal factors related to presentation and management, however, is far from certain. In an attempt to elucidate the importance of some of these factors, data from 383 live-born infants delivered at 26 to 30 weeks' gestation were analyzed. All infants were born in a tertiary perinatal unit and long-term follow-up had been carried out on the survivors for at least 1 year. A group of 39 infants who died in the neonatal period and 34 infants with long-term handicap were compared with matched normal control infants. Perinatal factors related to outcome were analyzed and it was found that, while initial poor condition at birth was correlated with death, there were few predictors of subsequent handicap. More refined methods of both prenatal and neonatal assessment are required to define these factors.

The survival of infants weighing less than 1000 grams depends on knowledgeable and concerned care based on an understanding of the limitations imposed by the immature kidney. This paper discusses renal constraints in caring for the very preterm infant, hormonal control of renal function, techniques for monitoring renal function, and renal problems commonly encountered in clinical management.

Lipase activity was quantitated in gastric aspirates of 7 premature infants (gestational age 24–29 weeks) during periods of total parenteral nutrition (TPN), mixed parenteral nutrition and gavage feeding or exclusive gavage feeding. The infants were studied from birth until the establishment of exclusive gastric gavage feeding. Lipase activity in gastric aspirates (quantitated by the hydrolysis of 3H-triolein at pH 4.2 and expressed in nmol 3H-oleic acid released/min/ml gastric aspirate) did not differ significantly as a function of mode of feeding: 570 ± 235 during TPN, 260 ± 145 during mixed parenteral nutrition and gavage feeding, and 374 ± 149 during exclusive gastric gavage feeding. The data suggest that, contrary to the intestine and pancreas, the digestive function of the stomach is not impaired during TPN in the very preterm infant.

A retrospective study was performed to determine the usefulness of intrapartum fetal heart rate patterns in managing infants of 26 to 30 weeks' gestational age by a comparison of intrapartum tracings with neonatal outcome. Fetal heart rate patterns of 26 infants who died were matched for gestational age with those of infants who did not die or demonstrate developmental abnormalities after a 1-year follow-up were analyzed. A normal fetal heart rate pattern was associated with a good outcome (p less than 0.05), the only deaths (three) being secondary to unrelated factors. An abnormal fetal heart rate tracing predicted 90% of deaths; however, an abnormal fetal heart rate tracing was also found in 15 of 31 infants with no mortality or morbidity. Evidence would thus suggest that the very preterm infant can tolerate the stress associated with normal labor and that a normal fetal heart rate pattern predicts good fetal outcome in the absence of unrelated perinatal abnormality. With significantly abnormal patterns, however, further parameters must be evaluated before the diagnosis of fetal distress associated with subsequent mortality can be made with certainty.

The range of thermal control and the thermoneutral range of preterm infants under 30 weeks' gestation was calculated by extrapolation of data from studies on more mature infants. Even assuming some thermoregulatory capacity, the range of control is less than 3 degrees C, the thermoneutral range is less than 0.5 degrees C, and both are greatly influenced by the rate of transepidermal water loss. Measurements of metabolic rate and effective thermal environment made on 6 infants under 30 weeks' gestation in the first week of life showed that the very preterm infant exerts little thermoregulatory control and that variations in transepidermal water loss are a major factor determining the appropriate thermal environment.

SummaryTwo separate episodes of rickets developed in a female infant of 25 weeks gestation and birthweight 690 g, who had congenital hypothyroidism and required parenteral nutrition for more than 100 days. We speculate that there is a relationship between metabolic bone disease of prematurity and the preterm infant’s thyroid status.

The effects of continuous positive airway pressure (CPAP) on pulmonary function during weaning from ventilator treatment were examined immediately after extubation in 17 very preterm infants, who had been ventilator-treated because of hyaline membrane disease (15 infants) and chronic pulmonary insufficiency of prematurity (two infants). Seven infants had bronchopulmonary dysplasia. Median birthweight was 920 g and median gestational age 26 completed weeks. The median duration of ventilator treatment was 10 days. Application of CPAP by means of a face chamber device after endotracheal extubation significantly lowered the frequency of apnea (P = 0.02) and enhanced oxygenation (P = 0.001). The respiratory mechanical indices derived from flow rate and juxta-diaphragmatic esophageal pressure measurements showed a reduced elastic (P = 0.03) and resistive (P = 0.02) load on the diaphragm. Even if the measured values do not accurately represent absolute resistances and compliances, the relative values of end-inspiratory and end-expiratory pressures differed significantly with and without CPAP (P = 0.001 and 0.002, respectively). We found CPAP applied via the face chamber technique immediately after extubation to be beneficial and to facilitate weaning from ventilator treatment in very preterm infants. Pediatr Pulmonol 1988; 4:213–218.

Background: The definition of late-onset bacterial sepsis (LOS) in very preterm infants is not unified. The objective was to assess the concordance of LOS diagnosis between experts in neonatal infection and international classifications and to evaluate the potential impact on heart rate variability and rate of “bronchopulmonary dysplasia or death”. Methods: A retrospective (2017–2020) multicenter study including hospitalized infants born before 31 weeks of gestation with intention to treat at least 5-days with antibiotics was performed. LOS was classified as “certain or probable” or “doubtful” independently by five experts and according to four international classifications with concordance assessed by Fleiss’s kappa test. Results: LOS was suspected at seven days (IQR: 5–11) of life in 48 infants. Following expert classification, 36 of them (75%) were considered as “certain or probable” (kappa = 0.41). Following international classification, this number varied from 13 to 46 (kappa = −0.08). Using the expert classification, “bronchopulmonary dysplasia or death” occurred less frequently in the doubtful group (25% vs. 78%, p < 0.001). Differences existed in HRV changes between the two groups. Conclusion: The definition of LOS is not consensual with a low international and moderate inter-observer agreement. This affects the evaluation of associated organ dysfunction and prognosis.

INTRODUCTION: Variation of respiratory care is described between centers around the world. The Italian Neonatal Network (INN), as a national group of the Vermont-Oxford Network (VON) allows to perform a wide analysis of respiratory care in very low birth weight infants. METHODS: We analyzed the dataset of infants enrolled in the INN in 2009 and 2010 and, for surfactant administration only, from 2006 to 2010 from 83 participating centers. All definitions are those of the (VON). A questionnaire analysis was also performed with a questionnaire on centers practices. RESULTS: We report data for 8297 infants. Data on ventilator practices and outcomes are outlined. Variation for both practices and outcome is found. Trend in surfactant administration is also analyzed. CONCLUSIONS. The great variation across hospitals in all the surveyed techniques points to the possibility of implementing potentially better practices with the aim of reducing unwanted variation. These data also show the power of large neonatal networks in identifying areas for potential improvement.

Preterm birth may result in adverse health outcomes. Very preterm infants typically exhibit postnatal growth restriction, metabolic disturbances, and exaggerated inflammatory responses. We investigated the differences in the meconium microbiota composition between very preterm ( 37 weeks) human neonates by 16S rRNA gene sequencing. Human meconium microbiota transplants to germ-free mice were conducted to investigate whether the meconium microbiota is causally related to the preterm infant phenotype in an experimental model. Our results indicate that very preterm birth is associated with a distinct meconium microbiota composition. Fecal microbiota transplant of very preterm infant meconium results in impaired growth, altered intestinal immune function, and metabolic parameters as compared to term infant meconium transplants in germ-free mice. This finding suggests that measures aiming to minimize the long-term adverse consequences of very preterm birth should be commenced during pregnancy or directly after birth.

Three studies of late outcome in groups of consecutively admitted very low birthweight or very pre-term infants have recently been reported from Rigshospitalet, Copenhagen. The periods were 1976–78, 1980–82, and 1984–87. The incidences of blindness due to retinopathy of prematurity (ROP) and of motor deficit due to cerebral palsy (CP) are analysed in this report. For the present purpose selection within the three groups made them more, although not entirely, comparable. In spite of marked changes in the use of mechanical ventilation, and in survival rate, the incidences of ROP as well as CP remained constant, at about 5% and 10% of the survivors, respectively. The actual numbers are too small for clearcut conclusions but the analysis supports two previously formed notions: 1) According to monitoring of blood gases deviating oxygen and carbondioxide tensions do not appear as prime factors in inducing neither ROP nor CP, and 2) a very preterm infant of given size and maturity has become less exposed to ROP and CP over the years.

A new method of quantifying cerebral blood flow which allows repeated cotside measurements is described. 31 observations were made on nine ill, mostly very preterm, infants. Cerebral blood flow was usually about 18 ml.100 g-1.min-1, but ranged from 7 ml.100g-1.min-1 (after the administration of indomethacin to a very preterm infant) to 33 ml.100 g-1.min-1 in a birth-asphyxiated post-term infant.

Cerebral autoregulation has been demonstrated in newborn animals. We studied the relationship between mean arterial pressure (MAP) and cerebral blood flow velocity (CBFV) in 90 stable preterm infants ≤32 weeks gestation. Mean (SD) gestational age was 28.9 (1.9) wks, birth weight 1,128 (230) grams, 5 min Apgar score 7.4 (0.9), and initial pH 7.36 (.08). All infants had been normoxic and normocarbic from birth onwards. Intracranial hemorrhage and patent ductus arteriosus were excluded. CBFV was determined at MAPs ranging from 27-50 mm Hg. Using 2-D/Doppler ultrasound, we obtained CBFV waveforms from the pericallosal (PCA), internal carotid (ICA), and basilar (BA) arteries between 12-72 hours of age. Peak systolic, end diastolic, and mean (MFV) flow velocities were derived from 3 consecutive cardiac cycles. A linear relationship between MAP and MFV was found in all 3 arteries: r=.76 in the PCA, r=.73 in the ICA, and r=.70 in the BA (p