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.     

Hyaline membrane disease,alkali, and intraventricular haemorrhage.

The relation between intraventricular haemorrhage (IVH) and hyaline membrane disease (HMD) was studied in singletons that came to necropsy at Hammersmith Hospital over the years 1966-73. The incidence of IVH in singleton live births was 3-22/1000 and of HMD 4-44/1000. Although the high figures were partily due to the large number of low birthweight infants born at this hospital, the incidence of IVH in babies weighing 1001-1500 g was three times as great as that reported in the 1658 British Perinatal Mortality Survey. Most IVH deaths were in babies with HMD, but the higher frequency of IVH was not associated with any prolongation of survival time of babies who died with HMD as compared with the 1958 survey. IVH was seen frequently at gestations of up to 36 weeks in babies with HMD but was rare above 30 weeks'' gestation in babies without HMD. This indicated that factors associated with HMD must cause most cases of IVH seen at gestations above 30 weeks. Comparison of clinical details in infants with HMD who died with or without IVH (at gestations of 30-37 weeks) showed no significant differences between the groups other than a high incidence of fits and greater use of alkali therapy in the babies with IVH. During the 12 hours when most alkali therapy was given, babies dying with IVD received a mean total alkali dosage of 10-21 mmol/kg and those dying without IVH 6-34 mmol/kg (P less than 0-001).There was no difference in severity of hypoxia or of metabolic acidosis between the 2 groups. Babies who died with HMD and germinal layer haemorrhage (GLH) without IVH had received significantly more alkali than those who died with HMD alone, whereas survivors of severe respiratory distress syndrome had received lower alkali doses than other groups. It is suggested that the greatly increased death rate from IVH in babies with HMD indicates some alteration of management of HMD (since 1958) as a causative factor. Liberal use of hypertonic alkali solutions is the common factor which distinguishes babies dying with GLH and IVH from other groups of babies with HMD. Although the causal nature of this association remains unproved, it seems justifiable to lrge caution in alkali usage.     

Hyaline membrane disease, alkali, and intraventricular haemorrhage

The relation between intraventricular haemorrhage (IVH) and hyaline membrane disease (HMD) was studied in singletons that came to necropsy at Hammersmith Hospital over the years 1966-73. The incidence of IVH in singleton live births was 3-22/1000 and of HMD 4-44/1000. Although the high figures were partily due to the large number of low birthweight infants born at this hospital, the incidence of IVH in babies weighing 1001-1500 g was three times as great as that reported in the 1658 British Perinatal Mortality Survey. Most IVH deaths were in babies with HMD, but the higher frequency of IVH was not associated with any prolongation of survival time of babies who died with HMD as compared with the 1958 survey. IVH was seen frequently at gestations of up to 36 weeks in babies with HMD but was rare above 30 weeks' gestation in babies without HMD. This indicated that factors associated with HMD must cause most cases of IVH seen at gestations above 30 weeks. Comparison of clinical details in infants with HMD who died with or without IVH (at gestations of 30-37 weeks) showed no significant differences between the groups other than a high incidence of fits and greater use of alkali therapy in the babies with IVH. During the 12 hours when most alkali therapy was given, babies dying with IVD received a mean total alkali dosage of 10-21 mmol/kg and those dying without IVH 6-34 mmol/kg (P less than 0-001). There was no difference in severity of hypoxia or of metabolic acidosis between the 2 groups. Babies who died with HMD and germinal layer haemorrhage (GLH) without IVH had received significantly more alkali than those who died with HMD alone, whereas survivors of severe respiratory distress syndrome had received lower alkali doses than other groups. It is suggested that the greatly increased death rate from IVH in babies with HMD indicates some alteration of management of HMD (since 1958) as a causative factor. Liberal use of hypertonic alkali solutions is the common factor which distinguishes babies dying with GLH and IVH from other groups of babies with HMD. Although the causal nature of this association remains unproved, it seems justifiable to lrge caution in alkali usage.     

Clinical events relating to intraventricular haemorrhage in the newborn.

Continuous measurements of arterial pressures, heart rates, respiratory movements, and respiratory rates were made from birth in 44 infants at risk from intraventricular haemorrhage (IVH). 17 babies died with IVH, in 10 of whom the event was timed objectively. Events in these babies were compared with survivors of similar birthweights, gestational ages, severity of birth asphyxia, and severity of hyaline membrane disease (HMD). IVH followed severe HMD and was associated with cessation of the babies' own respiratory efforts while on a ventilator and also with characteristic cardiorespiratory events. The minimum arterial pressure before IVH was lower than in comparable babies who survived. It is suggested that fluctuations of systemic blood pressure from initial low levels may be important in the pathogenesis of IVH. It is possible that changes in cerebral blood flow are of even greater significance.     

Cranial ultrasound screening of preterm and term neonates

A cranial ultrasound examination was performed between 48 and 96 h of age on 580 neonates of 25-42 weeks gestation. The incidence of cerebroventricular haemorrhage (CVH) in infants less than 32 weeks gestation was 37%, compared with an incidence of 2.7% in infants of 32 weeks or more. The incidence of CVH unselected healthy term infants (between 37 and 42 weeks) was only 1.1%. Of the 13 infants of 32 weeks or more who were found to have a haemorrhage, nine had a small (Grade I) haemorrhage (69%) and none of these infants had abnormal neurological signs in the neonatal period. The remaining four infants with Grade II, III or IV haemorrhage developed either seizures or episodes of apnoea. Two of the 13 infants of 32 weeks or more with a haemorrhage died, one during the newborn period and the other at 5.5 months of age. CVH in asymptomatic infants of 32 weeks or more gestation is uncommon and does not justify routine cranial ultrasound scanning.     

Cranial ultrasound screening of preterm and term neonates

Abstract A cranial ultrasound examination was performed between 48 and 96 h of age on 580 neonates of 25–42 weeks gestation. The incidence of cerebroventricular haemorrhage (CVH) in infants less than 32 weeks gestation was 37%, compared with an incidence of 2.7% in infants of 32 weeks or more. The incidence of CVH in unselected healthy term infants (between 37 and 42 weeks) was only 1.1%.
Of the 13 infants of 32 weeks or more who were found to have a haemorrhage, nine had a small (Grade I) haemorrhage (69%) and none of these infants had abnormal neurological signs in the neonatal period. The remaining four infants with Grade II, III or IV haemorrhage developed either seizures or episodes of apnoea. Two of the 13 infants of 32 weeks or more with a haemorrhage died, one during the newborn period and the other at 5.5 months of age.
CVH in asymptomatic infants of 32 weeks or more gestation is uncommon and does not justify routine cranial ultrasound scanning.     

Hypocarbia in the ventilated preterm infant and its effect on intraventricular haemorrhage and bronchopulmonary dysplasia

OBJECTIVE: To examine the relationship between PaCO2 levels in ventilated very preterm infants and (i) the incidence of severe intraventricular haemorrhage (IVH) and periventricular leukomalacia (PVL); and (ii) bronchopulmonary dysplasia (BPD). METHODS: A retrospective cohort analysis of preterm infants comparing PaCO2 levels with the incidence of severe IVH/PVL and BPD was carried out on patients born at less than 29 weeks gestation from 1992 to 1994 and admitted to the tertiary neonatal intensive care unit at the King Edward Memorial Hospital (314 infants). During the first 96 h, PaCO2 levels were examined including lowest and highest PaCO2 levels, mean PaCO2 levels and duration of hypocarbia both pre- and post-surfactant administration. RESULTS: Of the 314 infants, there were 40 early neonatal deaths (less than 48 h) who were not included in the analysis. Of the 274 surviving infants, 72 (26%) infants had severe IVH. Infants whose PaCO2 fell below 30 mmHg at any stage in the first 48 h of life had an increased risk of severe IVH or PVL (odds ratio 2.38; 95% CI 1.27-4.49; P = 0.007). Of the 265 survivors to 36 weeks corrected gestational age, 134 (51%) had BPD. Infants with at least three PaCO2 values less than 30 mmHg in the first 24 h of life had an increased risk of BPD (odds ratio 2.21; 95% CI 1.05-4.57; P = 0.036). CONCLUSIONS: The risk of severe IVH/PVL was significantly increased by hypocarbia. There was also an association between hypocarbia and BPD, particularly when hypocarbia was prolonged. These findings suggest that avoidance of hypocarbia may reduce the incidence of severe IVH/PVL and BPD in preterm infants.     

Developmental and neurological progress of preterm infants with intraventricular haemorrhage and ventricular dilatation.

A prospective neurological and developmental assessment was completed at ages 6, 9, and 12 months on 39 preterm infants under 34 weeks'' gestation. In the newborn period each infant had an assessment of gestation and sequential neurological and ultrasound examinations and was placed in one of three groups: intraventricular haemorrhage (IVH) (n = 14), IVH followed by ventricular dilatation (n = 11), and control infants with no evidence of IVH (n = 14). When corrected for prematurity the Griffiths''s developmental quotients (DQs) were normal at 6, 9, and 12 months for every infant except one aged 12 months. In contrast, the uncorrected DQs at 12 months were under 80 in only one of the 14 preterm infants without haemorrhage, compared with 2 of the 14 with IVH, and with 7 of the 9 with IVH and dilatation. There was also a higher incidence of neurological abnormality at each follow-up age in the infants with IVH plus ventricular dilatation, compared with those with IVH alone, or with infants without IVH. Similar differences were also demonstrated in 5 milestones reflecting gross motor, fine motor, and social or verbal development in the three groups at 6, 9, and 12 months. The neurological and developmental deficits seemed to relate more closely to the presence of post-haemorrhagic ventricular dilatation than to the size of the initial haemorrhage itself. These results may have important implications for therapeutic intervention in the management of newborn infants with IVH and ventricular dilatation.     

Thyroid function in very preterm infants

Indices of thyroid function were measured in 108 infants born at 23-31 weeks gestation, after birth, at 24 and 72 h, and at 1, 3, 4, 5 and 6 weeks of age. This group was characterised by low serum thyroxine (T4), normal thyroid stimulating hormone (TSH), low-normal thyroid binding globulin (TBG), low free thyroxine index (FTI) and low triiodothyronine (T3). The incidence of hypothyroxinaemia defined as a serum T4 value of less than 65 nmol/l was 58% after birth, increasing to 84% at 1 week, after which there was progressive reduction to 36% by 6 weeks of age. Mean T4 values were inversely proportional to gestational age during this study period. Infants of 23-28 weeks gestation had significantly lower T4, TBG, FTI and T3 values compared to those of 29-31 weeks gestation. Infants who had hyaline membrane disease (HMD) had significantly lower T4 and FTI values compared to those without HMD for up to 3 weeks of age. Similar differences were found between deaths and survivors in the first week after birth. This study suggests that there is increasing delay in maturation of the hypothalamic-pituitary-thyroid axis control with increasing prematurity. In addition, the data suggest that infants who were extremely preterm or those with HMD had worse and more persistent abnormalities of thyroid function secondary to their illness and metabolic stress. The significance of our findings, in particular that of prolonged hypothyroxinaemia, is uncertain. The role of thyroid replacement therapy in these very preterm infants therefore need to be assessed with a randomised clinical trial.     

Post-haemorrhagic hydrocephalus in the preterm infant

This prospective study documents the incidence, clinical features and risk factors for post-haemorrhagic hydrocephalus (PHH) as well as the short-term outcome after serial CSF taps. Serial real-time ultrasound scans were performed on 220 infants: on all admissions less than or equal to 1250 g and on an additional 130 infants with birthweights greater than 1250 g with risk factors for intraventricular haemorrhage (IVH). Based on percentile charts of postnatal increase in ventricular size and head circumference growth rate, PHH was defined as ventricular dilatation greater than 95th centile associated with either a head circumference growth greater than 95th centile or with clinical features of raised intracranial pressure (ICP). Forty-eight (22%) infants were found to have IVH of whom 14 had intracerebral extension of IVH. Sixteen (40%) of 40 infants who survived the acute episode of IVH developed PHH. PHH occurred more commonly in those who survived severe birth asphyxia and/or intracerebral extension of IVH. Fifteen infants who developed clinical features of raised ICP were treated with serial CSF taps. This procedure was effective in a staged treatment for PHH in relieving clinical symptoms and deferring ventriculo-peritoneal (VP) shunting. Morbidity associated with serial CSF taps and VP shunting is minimal. A high red cell count and protein concentration in the CSF at diagnosis of PHH identified all five infants who subsequently required VP shunting.     

Post-haemorrhagic hydrocephalus in the preterm infant

Abstract This prospective study documents the incidence, clinical features and risk factors for post-haemorrhagic hydrocephalus (PHH) as well as the short-term outcome after serial CSF taps. Serial real-time ultrasound scans were performed on 220 infants: on all admissions ≤1250 g and on an additional 130 infants with birthweights >1250 g with risk factors for intraventricular haemorrhage (IVH). Based on percentile charts of postnatal increase in ventricular size and head circumference growth rate, PHH was defined as ventricular dilatation >95th centile associated with either a head circumference growth >95th centile or with clinical features of raised intracranial pressure (ICP). Forty-eight (22%) infants were found to have IVH of whom 14 had intracerebral extension of IVH. Sixteen (40%) of 40 infants who survived the acute episode of IVH developed PHH. PHH occurred more commonly in those who survived severe birth asphyxia and/or intracerebral extension of IVH. Fifteen infants who developed clinical features of raised ICP were treated with serial CSF taps. This procedure was effective in a staged treatment for PHH in relieving clinical symptoms and deferring ventriculo-peritoneal (VP) shunting. Morbidity associated with serial CSF taps and VP shunting is minimal. A high red cell count and protein concentration in the CSF at diagnosis of PHH identified all five infants who subsequently required VP shunting.     

Hypercarbia at birth: a possible role in the pathogenesis of intraventricular hemorrhage.

To test the hypothesis that birth asphyxia has a role in the etiology of intraventricular hemorrhage (IVH), blood was collected from the umbilical artery (UA) at birth in 28 premature infants of 26 to 29 weeks gestation and analyzed for hydrogen ion concentration [H+], PCO2, standard bicarbonate level, and lactic acid level. The infants were followed up throughout their nursery stay until a diagnosis of IVH could be made or excluded, either by autopsy or clinical findings. Infants with IVH had lower Apgar scores. There were no differences in UA [H+] or bicarbonate or lactic acid levels. However, infants with IVH had a significantly higher UA PCO2. Although the difference appeared relatively small, the increase in PCO2 during labor may have been relatively large. It is concluded that hypercarbia, possibly by increasing cerebral blood flow, may be one important factor in the genesis of IVH.     

Effect of maternal tocolysis on the incidence of severe periventricular/intraventricular haemorrhage in very low birthweight infants.

AIM: To examine the relation between grade III-IV periventricular/intraventricular haemorrhage (PVH/IVH) and antenatal exposure to tocolytic treatment in very low birthweight (VLBW) premature infants. STUDY DESIGN: The study population consisted of 2794 infants from the Israel National VLBW Infant Database, of gestational age 24-32 weeks, who had a cranial ultrasound examination during the first 28 days of life. Infants of mothers with pregnancy induced hypertension or those exposed to more than one tocolytic drug were excluded. Of the 2794 infants, 2013 (72%) had not been exposed to tocolysis and 781 (28%) had been exposed to a single tocolytic agent. To evaluate the effect of tocolysis and confounding variables on grade III-IV PVH/IVH, the chi(2) test, univariate analysis, and a logistic regression model were used. RESULTS: Of the 781 infants (28%) exposed to tocolysis, 341 (12.2%) were exposed to magnesium sulphate, 263 (9.4%) to ritodrine, and 177 (6.3%) to indomethacin. The overall incidence of grade III-IV PVH/IVH was 13.4%. In the multivariate logistic regression analysis, the following factors were related significantly and independently to grade III-IV PVH/IVH: no prenatal steroid treatment, low gestational age, one minute Apgar score 0-3, respiratory distress syndrome, patent ductus arteriosus, mechanical ventilation, and pneumothorax. Infants exposed to ritodrine tocolysis (but not to the other tocolytic drugs) were at significantly lower risk of grade III-IV PVH/IVH after adjustment for other variables (odds ratio = 0.3; 95% confidence interval 0.2 to 0.6). CONCLUSION: This study suggests that antenatal exposure of VLBW infants to ritodrine tocolysis, in contrast with tocolysis induced by magnesium sulphate or indomethacin, was associated with a lower incidence of grade III-IV PVH/IVH.     

Periventricular haemorrhage and leukomalacia in extremely low birthweight infants

Forty (49%) of 82 extremely low birthweight (ELBW, less than 1000 g) infants had periventricular haemorrhage (PVH). Ten (12%) had germinal layer haemorrhage (GLH) alone, 16 (20%) had intraventricular haemorrhage (IVH) and 14 (17%) had intracerebral haemorrhage (ICH). Almost all the cases of PVH had developed by 4 days of age. Small-for-gestational age infants (12% of study population) had a significantly lower incidence and severity of PVH than appropriate-for-gestational age infants. Of 94 infants born between 23 and 28 weeks gestation, 45 (48%) had PVH. The PVH incidence was 60% in those of 23-26 weeks and 38% in those of 27-28 weeks. The hospital survival rate of ELBW infants was 69% in those without PVH and 43% in those with PVH; 70% in GLH alone; 50% in IVH and 14% in ICH. Three survivors developed post-haemorrhage hydrocephalus of whom two required ventriculoperitoneal shunting. Five survivors developed periventricular leukomalacia (PVL) evidenced by cysts identified between 3 and 7 weeks of age. A significant decrease in the incidence of PVH occurred over the study period (67% in 1982, 38% in 1983 and 33% in 1984). This decrease was seen for all grades of PVH. The reasons for this decreased incidence are still to be ascertained but this trend suggests that improvements in neonatal intensive care have the potential to improve the neurological outcome of more recent ELBW survivors.     

Intracranial haemorrhage in the preterm sheep fetus

The germinal layer in the brain of the sheep fetus at 58--85 days of gestation was found to resemble that of the human infant at 28--30 wk of gestation. Experiments were done on 65 exteriorized fetuses to explore the effect of various combinations of asphyxia and raised intravascular pressures in causing bleeding into the germinal layer, ventricles and other parts of the brain. Asphyxia by itself did not produce an increase in the incidence of intracranial hemorrhages when compared with control fetuses. The combination of asphyxia with intermittent increases in arterial or venous pressure, or both, did cause haemorrhages. Large increases in arterial pressure without asphyxia also caused intracranial haemorrhages, whereas increases in venous pressure without asphyxia did not. The types of haemorrhage observed closely resembled those seen in the preterm human infant, although massive intraventricular haemorrhages (IVHs) were rare. We conclude that: (1) the sheep fetus can be used for investigating factors associated with intracranial haemorrhage in the preterm brain; (2) the most effective method of producing haemorrhages into the germinal layer was by a combination of asphyxia with intermittent increases in cerebral intravascular pressure. Similar mechanisms may be at work in the newborn human infant, and could lead to IVH.     

Grade and laterality of intraventricular haemorrhage to predict 18-22 month neurodevelopmental outcomes in extremely low birthweight infants

Aim: To determine whether extremely low‐birthweight (ELBW) infants with bilateral compared to unilateral intraventricular haemorrhage (IVH) have worse neurodevelopmental outcomes at 18–22 months. Methods: A total of 166 ELBW infants (<1000 g) admitted to a Cincinnati NICU from 1998 to 2005 with a head ultrasound showing Grade I–IV IVH and neurodevelopmental assessment at 18–22 months corrected age were included. Multivariable linear and logistic regression models were developed to determine the impact of laterality and grade of IVH and other clinical variables to predict scores on the Bayley Scales of Infant Development, Second Edition, Mental Development Index and Psychomotor Development Index and the combined outcome of neurodevelopmental impairment (NDI). Results: Infants with bilateral grade IV IVH had lower adjusted mean Bayley scores compared with infants with unilateral grade IV IVH. For grades I, II and III IVH, bilaterality of IVH was not associated with lower mean Bayley scores. Infants with grade IV IVH had the highest odds of NDI. The probability of NDI increased with sepsis and postnatal steroid use. Conclusion: ELBW infants with bilateral compared to those with unilateral grade IV IVH had worse neurodevelopmental outcomes. Infants with grades I–III IVH had similar outcomes whether they had unilateral or bilateral IVH.     

早产儿脑损伤的患病率和危险因素

目的 探讨早产儿脑损伤的患病率和危险因素,为预防或降低早产儿脑损伤提供依据.方法 对2005年1月-2006年12月美国圣路易斯华盛顿大学儿童医院NICU收治的胎龄小于37周的早产儿的临床资料进行回顾性分析,按胎龄分组,计算脑损伤的患病率,采用多因素Logistic回归模型确立危险因素.结果 本组早产儿总的脑室内出血(IVH)和脑室周围白质软化(PVL)的患病率分别为17.7%和4.9%,而存活病例的患病率分别为14.4%和4.5%.按胎龄分组,IVH和PVL的患病率分别为:23~<25周龄组48.1% 和14.8%、25~<28周龄组35.2%和11.2%、28~<33周龄组13.8%和3.1%、33~<37周龄组2.8%和1.7%.坏死性小肠结肠炎、PDA、机械通气(MV)是IVH的独立危险因素,而胎龄、5 min Apgar评分为保护因素(负相关);IVH、MV、母亲产前或产时感染是PVL的危险因素,而出生体质量和女性为保护因素.同时IVH是导致早产儿死亡的危险因素.结论 胎龄越小,脑损伤的患病率越高;围生期感染、窒息缺氧以及影响脑血流的因素如PDA和MV等与早产儿脑损伤的发生密切相关.     

Periventricular haemorrhage and leukomalacia in extremely low birthweight infants

Forty (49%) of 82 extremely low birthweight (ELBW, <1000 g) infants had periventricular haemorrhage (PVH). Ten (12%) had germinal layer haemorrhage (GLH) alone, 16 (20%) had intraventricular haemorrhage (IVH) and 14 (17%) had intracerebral haemorrhage (ICH). Almost all the cases of PVH had developed by 4 days of age. Small-for-gestational age infants (12% of study population) had a significantly lower incidence and severity of PVH than appropriate-for-gestational age infants. Of 94 infants born between 23 and 28 weeks gestation, 45 (48%) had PVH. The PVH incidence was 60% in those of 23-26 weeks and 38% in those of 27-28 weeks. The hospital survival rate of ELBW infants was 69% in those without PVH and 43% in those with PVH; 70% in GLH alone; 50% in IVH and 14% in ICH. Three survivors developed post-haemorrhage hydrocephalus of whom two required ventriculoperitoneal shunting. Five survivors developed periventricular leukomalacia (PVL) evidenced by cysts identified between 3 and 7 weeks of age. A significant decrease in the incidence of PVH occurred over the study period (67% in 1982, 38% in 1983 and 33% in 1984). This decrease was seen for ail grades of PVH. The reasons for this decreased incidence are still to be ascertained but this trend suggests that improvements in neonatal intensive care have the potential to improve the neurological outcome of more recent ELBW survivors.     

Metabolism: Periventricular-Intraventricular Hemorrhage in Small Premature Infants

The incidence of periventricular-intraventricular hemorrhage (PVH/IVH) in small premature infants diagnosed by computerized tomographic scanning (CT) is 40–50%. Ultrasound brain scanning is now emerging as an alternative modality for diagnosing PVH/IVH as early as the first day of life. Portability of the equipment and lack of ionizing radiation make this method ideal for studying newborn infants in intensive care units. In the present study the diagnosis of PVH/IVH was made using CT and ultrasound. Infants with PVH/IVH were then compared with infants in whom no bleeding was detected. The relationship between selected obstetric, neonatal, asphyxia1 and therapeutic factors and PVH/IVH was studied in a group of small premature infants. Statistically significant associations with respiratory distress, ventilator therapy, low Apgar score and metabolic acidosis were observed, lending support to their role in the pathogenesis of PVH/IVH. The prognosis of small premature infants suffering from post-hemorrhagic hydrocephalus is probably related to the extent of the first insult and hemorrhage and the rate and extent of the development of subsequent hydrocephalus.     

Quantitative aspects of perinatal lung growth

Weight, DNA, protein, hydroxyproline and disaturated phosphatidylcholine (DSPC) content were investigated in lungs of 97 normally formed infants over an age range from 22 to 75 postconceptional weeks, including 25 cases of hyaline membrane disease (HMD) and 13 small-for-dates infants (SFD). Lung weight and lung DNA relative to body weight were markedly lower in infants who died at 37-41 weeks than in those who died at shorter gestations or in early infancy. Total lung DSPC and DSPC concentration had a narrow peak at 36-41 weeks. The DSPC concentration per milligram of lung DNA in the first few months of infant life was similar to that in infants at 24 weeks gestation. Lung protein concentrations increased steadily but were variable at all ages. SFD infants had significantly higher concentrations of hydroxyproline and showed a peak DSPC concentration at an earlier gestation than the normals. Lungs of HMD infants showed some increase in hydroxyproline concentration but little other quantitative evidence of difference from the normals. We suggest that the relatively small lung size in many infants who die near term may result from recurrent intrauterine stress. Lung changes in small for dates infants are compatible with an advance in lung maturation, while the increased hydroxyproline concentration in the lungs of cases of HMD implies an early proliferative response to lung injury.