Reduction in periventricular haemorrhage in preterm infants.

Our previous cerebral ultrasound study of antecedents of periventricular haemorrhage in infants weighing 1250 g or less at birth suggested that neonatal events that caused increased or fluctuating cerebral blood flow lead to periventricular haemorrhage. As the risk period for this type of haemorrhage was the first four days of life strict guidelines were introduced to avoid the previously identified neonatal risk factors. No attempt was made to modify obstetric practice. Over the next two years, although the obstetric risk profile, the frequency and severity of hyaline membrane disease, and the gestation, birth weight, and sex distributions of a similar cohort of infants did not change, the incidence of periventricular haemorrhage decreased significantly from 60% to 36%. Significant antecedents of haemorrhage similar to those found in the previous study included severe bruising, low arterial:fractional inspiratory oxygen ratio and low packed cell volume on admission, hyaline membrane disease, hypercarbia, and hypoxaemia. Assisted ventilation, pneumothorax, treatment with tubocurarine, and hypotension were no longer significant risk factors for periventricular haemorrhage. A multivariate discriminant analysis correctly predicted haemorrhage in 86% of the study group when bruising, hypercarbia, hypoxaemia, hyaline membrane disease, and low gestation were considered. These results suggest that changes in neonatal practices can reduce the incidence of periventricular haemorrhage and that drug studies indicating similar reduction in haemorrhage need to be evaluated carefully to ensure that placebo and treated groups are in fact comparable.     

Timing and antecedents of periventricular haemorrhage and of cerebral atrophy in very preterm infants

The brains of 95 consecutively admitted infants born at less than 33 weeks gestation were scanned with ultrasound. Thirty-six (38%) had periventricular haemorrhage (PVH). Eight (8%) had cerebral atrophy (together with PVH in 5).Twelve (40%) of the 30 infants in whom satisfactory timing of PVH was possible bled on the first day of life, but the median age when PVH was first detected was during the second day. The median age when PVH reached its maximum extent was the fourth day. The most significant antecedents of PVH were very short gestation and the presence of severe respiratory illness, particularly hyaline membrane disease, necessitating mechanical ventilation. Analysis of variance showed that pneumothorax arising during ventilation was the single most significant antecedent of PVH. Other significant antecedents, notably prolonged coagulation times, were found almost exclusively in infants with severe respiratory illness.Cerebral atrophy appeared usually to be attributable either to severe asphyxia during delivery or later, or to the formation of cysts at the site of previous haemorrhage into brain tissue.     

Perinatal factors and adverse outcome in extremely low birthweight infants.

Perinatal factors associated with death or disability at 2 years were identified in an inborn cohort of 196 live births with a birth weight of 500-999 g. Antepartum haemorrhage, multiple pregnancy, breech presentation, perinatal asphyxia, hypothermia on admission, hyaline membrane disease, persistent pulmonary hypertension, severe respiratory failure, and intraventricular haemorrhage were associated with increased mortality. Factors associated with increased survival included maternal hypertension, caesarean birth, increasing maturity or size at birth, female sex, and fetal growth retardation. Stepwise multiple discriminant function analysis showed that six factors correctly classified the outcome in 83% of infants: intraventricular haemorrhage was the most important factor followed by the presence of acidosis and hypoxia in the early neonatal period, birth weight, pre-eclamptic toxaemia, and caesarean birth. This study also showed that intraventricular haemorrhage, seizures, antepartum haemorrhage and delay in regaining birth weight were associated with increased disability among survivors.     

Underestimation of arterial oxygen tension by transcutaneous electrode with increasing age in infants.

To investigate the effect of increasing gestational and postnatal age on the relation between transcutaneous oxygen tension (tcPO2) and arterial oxygen tension (PaO2) 160 simultaneous measurements of tcPO2 and PaO2 tensions were made on 42 infants born at 24-41 weeks'' gestation and aged 0-32 weeks from birth. Irrespective of gestational age a progressive fall in the tcPO2:PaO2 ratio with increasing postnatal age was found. At all postnatal ages tcPO2:PaO2 tended to be lower in the more mature infants.     

Hyaline Membrane Disease: I: Cellular Changes

Cellular changes were studied in 1 μ thick sections of lungs from 84 perinatal deaths, including 44 with hyaline membrane disease (HMD). The presence or absence of osmiophilic granules was related to surface tension measurements in 69 cases. The presence of numerous granules usually indicated normal surfactant and their absence a lack. It is concluded that the granules represent surfactant material.Osmiophilic granules were found first at 20 weeks'' gestation (in 2 out of 6 fetuses). After 24 weeks'' gestation almost all infants had many granules, except those with HMD.The earliest stages in hyaline membrane formation consisted of interstitial oedema accompanied by localized areas of necrosis and desquamation of alveolar epithelial cells. Osmiophilic granules were virtually absent.Infants dying at a later stage of the disease showed more extensive hyaline membranes, but from 36 hours almost all cases displayed some signs of repair of the denuded alveolar surfaces. In 5 out of 10 cases with evidence of repair, normal values for surface tension were obtained.In the late stages of HMD some of the cells lining the alveoli were highly abnormal. They consisted of large thick squames with very few capillaries in apposition to them; the appearances were thus consistent with a severe degree of alveolo-capillary block.     

Risk factors associated with the development of peri-intraventricular haemorrhage and periventricular leukomalacia

81 preterm infants of 34 weeks' gestation or less were prospectively and sequentially examined by means of real-time ultrasound in order to identify which clinical risk factors might be associated with the development of peri-intraventricular haemorrhage (PVH) and periventricular leukomalacia (PVL). Infants were allocated in three groups: group A (n = 44): with normal scans; group B (n = 24): with isolated PVH, and group C (n = 13): with PVL. 28 obstetrical and neonatal factors were compared within the three groups using two methods of statistical analysis (2 x 2 chi 2 analysis and multivariate logistic regression analysis). Hyaline membrane disease, acidosis, pneumothorax and Apgar score at 10 min were statistically associated with PVH. The multivariate logistic regression analysis showed that need for resuscitation, hyaline membrane disease, acidosis and gestational age were the most important factors. Gestational age, seizures, hyaline membrane disease, apnoea with hypoxaemia and bradycardia were strongly associated with PVL. These results suggest that a low gestational age, the need for resuscitation and a respiratory distress syndrome with its consequences might lead to PVH, whereas a low gestational age, hypoxaemia and cardiocirculatory disturbances might decrease cerebral perfusion and result into PVL.     

Intraventricular haemorrhage in the preterm infant without hyaline membrane disease.

The clinicopathological associations of 33 singleton infants who died with intraventricular haemorrhage (IVH) without hyaline membrane disease (HMD) (''IVH only'') were compared with those of 39 infants who died with IVH+HMD over the same gestation range in order to determine what factors other than those related to HMD may contribute to the pathogenesis of IVH. The incidence of ''IVH only'' was inversely related to gestational age in the Hammersmith birth population, whereas the incidence of IVH+HMD rose to a peak at 28-29 weeks'' gestation. Infants with ''IVH only'' lived longer on average than those with IVH+HMD despite a lower birthweight and shorter gestation. Infants who died in the first 12 hours from ''IVH only'' had suffered severe birth asphyxia but in those who died later the main symptom was recurrent apnoea. Fewer infants with asphyxia but in those who died later the main symptom was.recurrent apnoea. Fewer infants with ''IVH only'' were given alkali therapy or were connected to the ventilator as compared to those with IVH+HMD, but there were no differences in alkali therapy in those who lived for 12 hours or more. In the ''IVH only'' group there was a high incidence of haemorrhage from other sites and of bacterial infections. It is suggested that, in the absence of HMD, extreme immaturity is the main factor determining the occurrence of IVH. Birth asphyxia, apnoeic attacks, haemorrhage, and infections may play subsidiary roles, possibly through development of metabolic acidosis.     

Hospital admissions in the first year of life in very preterm infants

OBJECTIVE: To analyse hospital readmissions to 1 year in infants < 33 weeks' gestation. STUDY DESIGN: Cohort of very preterm infants born in Western Australia. METHODS: Parental social class, history of asthma, race, gestational age, birthweight, sex, severity of respiratory disease and oxygen requirement at 28 days chronic lung disease (CLD), 36 weeks and term, maternal smoking, cohabitation with siblings, breast-feeding duration and hospital readmissions were recorded prospectively. RESULTS: Data were available for 538 of 560 (96%) infants discharged. Eight died in the first year. Two hundred and twenty-five infants (42%) had 443 readmissions, of which 370 were medical and 73 surgical. Risk factors for medical readmission were Aboriginal race, male sex and CLD. Breast-feeding was protective. Risk factors for surgical admission were male sex, lower gestation, severe hyaline membrane disease, severe CLD and birthweight < 10th centile. CONCLUSIONS: Readmission is common after very preterm birth. Risk factors for medical and surgical admission differ with CLD being the only perinatal factor associated with both medical and surgical admission.     

Hyaline Membrane Disease: II: Lung Lecithin

The lecithin content of lung, together with its surface tension properties, were determined in 34 stillbirths, and 61 neonatal deaths. Lecithin content ranged widely from 1·5 to 18·6% of dry lung tissue.In 24 cases the `palmitic-lecithin'' was also measured; it formed 44-79% of the total lecithins. Since the two were related linearly, changes in palmitic-lecithin could be adequately studied by measuring total lecithins.Lecithin content was negatively correlated with minimum surface tension of lung extract in both fresh stillbirths and neonatal deaths. Cases with hyaline membranes had lung lecithin in the lower range (< 8% dry tissue). Lung lecithin content may be a measure of surfactant reserve.After 29 weeks'' gestation, fresh stillbirths and neonatal deaths, other than those with hyaline membranes, had normal lung surfactant. The exception was a small group of infants having immature lungs lacking surfactant, and who survived less than 2½ hours; some of these, it is surmised, would have developed hyaline membranes had they survived longer. This was consistent with the fact that well-formed hyaline membranes were only found in infants that had survived for at least 3 hours.Surfactant deficiency probably develops only after birth (except in very immature infants), and as a consequence of an initial rapid consumption of surfactant to form a lining layer covering the alveolar surface, when a gas-liquid interface is created by aeration of lung. Surfactant deficiency, by promoting interstitial pulmonary oedema, is thought to be the immediate cause of hyaline membrane disease.A scheme for the pathogenesis of hyaline membrane disease is set out. It provides a possible mechanism for the different ways in which surfactant deficiency may arise in immature and mature infants.Cases where hyaline membranes occur with normal surfactant fall into three groups: (1) Cases with hyaline membrane disease that have survived several days, the lungs being in the stage of repair. (2) Cases with massive lung haemorrhage, with severe anaemia from haemolytic disease, or with heart failure; extravasation of oedema fluid or blood may be the common factor in this group. (3) Infants of diabetic mothers.     

Reducing hypothermia in preterm infants with polyethylene wrap

Background: Occlusive plastic applied immediately after birth to reduce evaporative heat loss has been proven effective in preterm infants <28 weeks' gestation. However its effectiveness on preterm infants >28 weeks' gestation has not been shown. This study aimed to determine the effect of occlusive wrap at birth on the temperature at neonatal intensive care unit (NICU) admission among infants of greater than or equal to 24 weeks' and less than 34 weeks' gestation. Methods: Study infants were randomly assigned to “wrap” or “control” groups. Newborns in the wrap group were wrapped with polyethylene plastic sheets within the first min after birth. Infants randomized to the control group were dried immediately after birth with warmed towels under a warmer, according to the guidelines of Neonatal Resuscitation. Infants' axillary temperatures were measured on admission to the NICU, and after having been stabilized in incubators in the NICU. Results: A total of 110 infants were recruited into the study. The mean admission temperature was significantly higher in the wrap group (35.8 vs 34.8°C, P < 0.01). Admission hypothermia (axillary temperature <36.5°C) was present in 38 (78%) and 58 (98%) infants in the wrap and control groups, respectively. Among infants of <28 weeks' gestation, the post‐stabilization temperature was significantly higher in the wrap group. Conclusions: Wrapping premature infants with gestational age <34 weeks in polyethylene plastics immediately after birth is associated with lower incidence of hypothermia.     

THE HYALINE MEMBRANE DISEASE–INTRAVENTRICULAR HEMORRHAGE RELATIONSHIP IN THE VERY LOW BIRTH WEIGHT INFANT: PERINATAL ASPECTS

ABSTRACT. A large retrospective clinical study is reported confirming pathologic studies upon the effect of hyaline membrane disease on the occurrence of intraventricular hemorrhage in very low birth weight infants. Two hundred and twenty infants with birth weight 1500 g and gestational age 32 weeks were studied. Infants with hyaline membrane disease (112) had 56 % incidence of intraventricular hemorrhage whereas of those without hyaline membrane disease (108) only 31% developed intraventricular hemorrhage ( p < 0.001). When controlled for gestational age, the more immature infants ( 1000 g) exhibited no difference in the occurrence of intraventricular hemorrhage whether hyaline membrane disease coexisted or not. In the 1001–1500 g group, the occurrence of hyaline membrane disease with intraventricular hemorrhage was significant ( p < 0.001). The association of lower Apgar scores and the influence of intermittent positive pressure ventilation in infants with intraventricular hemorrhage is discussed. Extreme immaturity negates all perinatal clinical expertise in determining neonatal outcome. Therefore, carrying pregnancies beyond 28 weeks gestation is mandatory. Beyond 28 weeks, pulmonary maturity and the influence of therapeutic modalities and maternal transport become increasingly important.     

Nasal continuous positive airway pressure. Improvement in arterial oxygenation in hyaline membrane disease.

Continuous positive airway pressure (CPAP) was employed using nasal prongs in 30 neonates with hyaline membrane disease (HMD). There was a significant improvement in mean PaO2 (from 47 to 80 mmHg;p less than 0.001) with no significant change in PaCO2 or pH within a mean 36 min of therapy. Use of the technique allowed reduction of FiO2 to less than 0.60 in less than 20 h in 18 infants. Infants treated within 24 h of birth had significantly greater improvements in PaO2. Complications were infrequent and only 3 of 30 babies developed a pneumothorax while on nasal CPAP. Only 1 of the 23 survivors required mechanical ventilation in addition to nasal CPAP.     

Transcutaneous Measurement of Oxygen Tension in Infants with Hyaline Membrane Disease

Barr, P. A. (1979). Aust. Paediatr. J. , 15, 3–6. Transcutaneous measurement of oxygen tension in infants with hyaline membrane disease . Transcutaneous oxygen tension (tcPO2) using the Roche electrode, was compared with arterial oxygen tension (PaO2) from an indwelling arterial catheter or cannula in thirty-two infants with hyaline membrane disease. tcPO2 monitoring was performed by neonatal intensive care nurses for as long as seven days. Although the correlation of tcPO2 with PaO2 was good (r 0.713, P <.001), the tcPO2 monitor frequently failed to detect hypoxaemia and hyperoxaemia. Seventy-eight per cent of recorded PaO2 values < 50 mmHg were associated with tcPO2 values ≥ 50 mmHg and 41% of PaO2 values > 90 mmHg were associated with tcPO2 values ≤ 90 mmHg. tcPO2 measurement was not an acceptable alternative to PaO2 measurement. The incidence of hyperoxaemia in seven tcPO2 monitored infants with severe hyaline membrane disease (HMD) (5%) was significantly less than in five unmonitored infants with equally severe HMD (32%) (X², P < .001). tcPO2 monitoring was useful as a PaO2 trend recorder.     

Risk factors in the development of intraventricular haemorrhage in the preterm neonate.

One hundred and forty-six infants of 34 weeks'' gestation or less were repeatedly scanned by means of real-time ultrasound to diagnose the presence of intraventricular haemorrhage (IVH), its severity, and the timing of onset of the condition. We describe a new method for grading the extent of the IVH which does not depend on ventricular size. IVH was clearly present in 52 (36%) of the 146 infants and in 32 (50%) of the 64 infants of 30 weeks'' gestation or less. Repeated scans accurately timed the onset of IVH in 41 infants, and 32 (78%) had the first sign of IVH before 72 hours of age. Thirty-two clinical factors were analysed for possible correlation with the development of IVH: outborn compared with inborn, administration of sodium bicarbonate, hypothermia, intermittent positive pressure ventilation, continuous positive airways pressure, hypercapnia, severe acidosis, and respiratory distress syndrome all reached statistical significance. Analysis of variance showed that respiratory distress syndrome was the most important factor, but severe acidosis had some independent action on the development of IVH. Seventeen (81%) of 21 infants with hypercapnia (PCO2 greater than 6 kPa) together with severe acidosis (pH less than 7.1) developed IVH, of which more than half was moderate or severe in degree.     

Prevention of intraventricular haemorrhage by fresh frozen plasma.

Seventy three preterm infants weighing less than 1500 g or less than 32 weeks'' gestation, or both, were allocated randomly to treatment (fresh frozen plasma 10 ml/kg on admission and at 24 hours of age) or control groups. Fifteen (41%) out of 37 control patients sustained intraventricular haemorrhage compared with five (14%) of 36 patients receiving treatment (X2 = 5.24, P = 0.022). No difference was found in coagulation factors measured at birth or at 48 hours of age in both groups. Fresh frozen plasma appears to have a beneficial effect in the prevention of intraventricular haemorrhage.     

The hyaline membrane disease-intraventricular hemorrhage relationship in the very low birth weight infant: perinatal aspects

A large retrospective clinical study is reported confirming pathologic studies upon the effect of hyaline membrane disease on the occurrence of intraventricular hemorrhage in very low birth weight infants. Two hundred and twenty infants with birth weight less than or equal to 1 500 g and gestational age less than or equal 32 weeks were studied. Infants with hyaline membrane disease (112) had 56% incidence of intraventricular hemorrhage whereas of those without hyaline membrane disease (108) only 31% developed intraventricular hemorrhage (p less than 0.001). When controlled for gestational age, the more immature infants (less than or equal to 1 000 g) exhibited no difference in the occurrence of intraventricular hemorrhage whether hyaline membrane disease coexisted or not. In the 1 001-1 500 g group, the occurrence of hyaline membrane disease with intraventricular hemorrhage was significant (p less than 0.001). The association of lower Apgar scores and the influence of intermittent positive pressure ventilation in infants with intraventricular hemorrhage is discussed. Extreme immaturity negates all perinatal clinical expertise in determining neonatal outcome. Therefore, carrying pregnancies beyond 28 weeks gestation is mandatory. Beyond 28 weeks, pulmonary maturity and the influence of therapeutic modalities and maternal transport become increasingly important.     

Timing and evolution of periventricular haemorrhage in infants weighing 1250 g or less at birth.

The brains of 50 consecutively admitted infants who weighed 1250 g or less at birth were examined with real time ultrasound. Of 30 (60%) who had periventricular haemorrhage (PVH), 19 (63%) bled on the first day and 17 (57%) showed extension of the initial haemorrhage on serial scans. The median age was 16 hours when PVH was first detected and 48 hours when PVH reached its maximum extent. Ventricular size at birth correlated with gestation. Progressive ventricular growth was seen after birth in infants both with and without PVH. Charts of normal ranges of ventricular size and head circumference were drawn up from birth to 10 weeks of age. All infants with PVH showed a transient increase in ventricular size at 2 weeks of age but most returned to normal by 6 weeks of age. Ventricular dilatation after PVH that was greater than the 95th centile for this population developed in 5 (31%) of 16 survivors, four of whom subsequently developed hydrocephalus, although none required ventriculo peritoneal shunting. The optimal timing for diagnosis with ultrasound is at the end of the first week for PVH and the second to third week for ventricular dilatation.     

Predictive value of umbilical artery pH in preterm infants

Compared with term infants, little information is available about the usefulness of the umbilical artery pH in relation to outcome in extremely preterm infants. This prospective study evaluates the relation between umbilical artery pH (UapH), Apgar scores, perinatal events, and outcome in infants born at less than 32 weeks' gestation. Six hundred and twenty three infants of < 32 weeks' gestation were studied. The median UapH was 7.25, with a range of 6.78-7.49. A low UapH was significantly associated with male sex, hyaline membrane disease, grade 3 or 4 intraventricular haemorrhage, and neonatal death. It was also associated with lower birth weight and lower birthweight centile. The relations between the UapH and outcomes of neonatal death, cerebral palsy, and developmental quotient at 1 year, and other perinatal risk factors were then examined using multiple logistic regression. After adjusting for other risk factors, UapH was not significantly associated with any outcome. In contrast, a low one minute Apgar (< 4) remained a significant risk factor, with odds ratios of 2.7 (95% confidence interval (CI) 1.5 to 5.2) for neonatal death and 3.8 (95% CI 1.4 to 10.4) for cerebral palsy.     

Periventricular haemorrhage: Association with patent ductus arteriosus and its treatment with Indomethacin or surgery

Abstract A prospective study on 150 infants with a birthweight of 1250 g or less was carried out to investigate the effects of patent ductus arteriosus (PDA), haemorrhagic pulmonary oedema (HPO), Indomethacin therapy and surgical ligation on the development of periventricular haemorrhage (PVH) or the extension of pre-existing PVH. The incidence of PVH, diagnosed by serial cerebral ultrasonography was 44% and the incidence of PDA, diagnosed by serial M-mode and contrast echocardiography, was 45%. During the first 8 days after birth when the infants were vulnerable to PVH, the development of PDA did not lead to the development or extension of PVH in 85% of infants. Haemorrhagic pulmonary oedema also had no effect on PVH in 71% of infants. Compared with infants whose PDA or HPO had no effect on PVH, those who had development or extension of haemorrhage had significantly more severe hypercapnia, blood gas instability and hypotension associated with the occurrence of PDA or HPO. Early Indomethacin therapy was not associated with the development or extension of PVH in 93% of infants. Although an elevation of arterial blood pressure was demonstrated after ductal ligation, surgery was performed after 1 week of age in all infants and in no instance was there an effect on PVH. This study suggests that PDA leads to PVH only if it causes significant blood gas and blood pressure disturbances which are known to affect cerebral blood flow adversely.     

Periventricular haemorrhage: association with patent ductus arteriosus and its treatment with indomethacin or surgery

A prospective study on 150 infants with a birthweight of 1250 g or less was carried out to investigate the effects of patent ductus arteriosus (PDA), haemorrhagic pulmonary oedema (HPO), Indomethacin therapy and surgical ligation on the development of periventricular haemorrhage (PVH) or the extension of pre-existing PVH. The incidence of PVH, diagnosed by serial cerebral ultrasonography was 44% and the incidence of PDA, diagnosed by serial M-mode and contrast echocardiography, was 45%. During the first 8 days after birth when the infants were vulnerable to PVH, the development of PDA did not lead to the development or extension of PVH in 85% of infants. Haemorrhagic pulmonary oedema also had no effect on PVH in 71% of infants. Compared with infants whose PDA or HPO had no effect on PVH, those who had development or extension of haemorrhage had significantly more severe hypercapnia, blood gas instability and hypotension associated with the occurrence of PDA or HPO. Early Indomethacin therapy was not associated with the development or extension of PVH in 93% of infants. Although an elevation of arterial blood pressure was demonstrated after ductal ligation, surgery was performed after 1 week of age in all infants and in no instance was there an effect on PVH. This study suggests that PDA leads to PVH only if it causes significant blood gas and blood pressure disturbances which are known to affect cerebral blood flow adversely.