Intracranial Hemorrhage In Premature Infants Research Articles

Epidemiologic association between maternal smoking during pregnancy and intracranial hemorrhage in preterm infants

The objective of this study was to evaluate the effect of maternal smoking during pregnancy on the risk of intracranial hemorrhage in preterm infants (born at 24 to 33 weeks of gestation). We conducted a case-control study of 96 preterm infants with intracranial hemorrhage and 96 gestational age–matched control subjects with negative cranial ultrasonographic findings. In conditional multiple logistic regression models, heavy maternal smoking (>10 cigarettes per day) during the latter half of pregnancy was associated with an increased risk of mild (grade I or II) intracranial hemorrhage (odds ratio = 5.96, 95% confidence interval 1.72 to 20.76; p = 0.005). After adjustment for the confounding effect of birth weight and respiratory distress syndrome, the risk of any intracranial hemorrhage (grade I to IV) was three times higher (adjusted odds ratio = 3.63, 95% confidence interval 1.37 to 9.63; p = 0.009) in infants of heavy smokers (>10 cigarettes per day) than in control subjects. The results of this study indicate that cigarette smoking during the latter half of pregnancy increases the risk of intracranial hemorrhage in preterm infants. The deleterious effect of smoking was greater for mild hemorrhages (grade I or II) and was confined to infants of heavy smokers. (J P EDIATR 1995;127:472-8)

Sonography of the brain in infants: role in evaluating neurologic abnormalities.

Three primary imaging techniques are currently available for evaluating CNS disease in the infant: sonography, CT, and MR imaging. No one technique is optimal in all situations. An integrated approach may be the most appropriate and cost-effective. Sonography plays a role in screening for and following up intracranial hemorrhage in premature infants, in diagnosing congenital malformations of the brain, and in the initial diagnosis and follow-up of infants with hydrocephalus. Sonography can be used to diagnose periventricular leukomalacia and hypoxic/ischemic injury, but it is relatively insensitive in the acute phase. Doppler sonography plays a role in determining if a structure is vascular, such as vein of Galen aneurysm, and in assessing embolization of a vascular malformation. Doppler sonography also can be used at the bedside to diagnose suspected thrombosis of intracranial vessels. The purpose of this essay is to review the role of sonography in the diagnosis, treatment, and follow-up of these conditions.

Antenatal phenobarbital for the prevention of periventricular and intraventricular hemorrhage: A double-blind, randomized, placebo-controlled multihospital trial

To determine whether the neuroprotective properties of phenobarbital would alter the incidence and severity of intracranial hemorrhage in premature infants, we randomly assigned 110 women at less than 31 weeks of gestation to receive 10 mg/kg phenobarbital or placebo in a blinded fashion before delivery. Infants were examined postnatally with real-time ultrasonography for evidence of intracranial hemorrhage. Maternal demographics, pregnancy complications, antenatal management, and route of delivery did not differ between the phenobarbital group (n = 50) and the placebo group (n = 60). The total incidence of periventricular-intraventricular hemorrhage did not differ between the phenobarbital-treated (n = 54) and the placebo-treated (n = 67) infants. However, the frequency of grade 3 and grade 4 hemorrhages was 15% (10 infants) in the placebo group and 3.7% (2 infants) in the phenobarbital group (p less than 0.05). There were no differences in the severity of associated conditions in the babies to explain the difference in the incidence of severe hemorrhage between the study groups. We conclude that antenatal administration of phenobarbital appears to be effective in decreasing the severity of periventricular-intraventricular hemorrhage in infants delivered at less than 31 weeks of gestation.

Antithrombin III administration in premature infant with intracranial hemorrhage

Intracranial hemorrhage (ICH) is a significant cause of mortality and morbidity in the neonatal intensive care unit. Abnormalities of coagulation have been implicated as one of the important causes of intracranial hemorrhage in premature infants. Recent advances in the technique of ultrasound diagnosis of ICH in premature infants have made it possible for us to determine the presence of ICH even in the early stages of the disease. This study was conducted to ascertain whether antithrombin III (AT III) inhibits the progress of ICH in prematurely born infants.

Intracranial Hemorrhage in Premature Infants

Sir .—Meidell et al 1 have shown that of 40 premature infants, representing all inborn patients admitted to their service over a 12-month period, 15 (38%) experienced an intracranial hemorrhage (ICH) at a mean time of 1.9 hours after birth. The SE of the mean was 0.2 hours, which suggests that the hemorrhages were clustered into a reasonably small range. While their data may be accurate, we feel that it may not be representative of other investigators' observations. We have been conducting a study involving all admissions to our highrisk nursery over the past ten months. In that period, 94 infants weighing less than 1,500 g were admitted and received sonograms within 12 hours. Five (5.3%) of the infants (three inborn) had sustained an ICH. Two previous studies 2,3 demonstrated that only 5% to 10% of all admissions hemorrhaged within 12 hours. A fourth study, 4 which entered alternate patients and included

Rheological Properties of Blood and their Possible Role in the Circulation and Development of Intracranial Hemorrhage in Preterm Infants

Blood viscosity and other rheological properties of blood have important effects on blood circulation. In preterm infants, blood viscosity (at given hematocrit), plasma viscosity and red cell aggregation are decreased compared to term neonates and adults. In addition, the Fahraeus-Lindqvist effect (i.e., decrease in blood viscosity with decreasing vessel diameter) is more pronounced in preterm infants. This suggests that blood flow through arteries, arterioles and veins is facilitated in preterm infants. The large neonatal red cells are less filterable and less able to enter small capillaries than adult red cells. This suggests that the passage of neonatal red cells through narrow capillaries and splenic pores is impaired. The high risk of intracranial hemorrhage in small preterm infants may in part result from poor red cell aggregation, impeded passage of their large red cells through narrow cerebral capillaries and raised blood viscosity due to rapid transfusion of adult blood.

Perinatal factors associated with early-onset intracranial hemorrhage in premature infants. A prospective study.

Serial ultrasound examinations were performed on 40 consecutive newborn infants less than 35 weeks' gestational age. Fifteen of 17 infants with intracranial hemorrhage (ICH) had evidence of hemorrhage on the first ultrasound examination (mean age, 1.9 +/- 0.2 hours post partum). Comparing the clinical course of these 15 infants with age- and weight-matched non-hemorrhage controls showed a significant association between the occurrence of early ICH and the pattern of labor. There was no correlation between ICH and the mode of delivery, the use of sodium bicarbonate, volume administration, or the initial BP. In nine of the 15 infants with early-onset ICH, the hemorrhage progressed in severity during the first three postpartum days in association with increasing ventilatory requirements. The results of this study suggest that the course of labor may be a precipitating factor in the onset and evolution of early ICH.

Progressive ventriculomegaly following minor intracranial hemorrhage in premature infants.

Progressive hydrocephalus following subependymal-intraventricular hemorrhages (SEH-IVH) in premature infants has been noted after moderate to severe degrees of hemorrhage. The ventricular dilatation often has been noted to resolve spontaneously, or not continue to progress after four weeks of age. 11 premature infants with moderate to marked degrees of ventricular enlargement following minor degrees of SEH-IVH have been identified over an 18-month period, and in six of these infants the dilatation continued to progress after one month of age. This sequence of events has not been well documented, and it emphasizes the need to closely follow all infants who have sustained any degree of intracranial hemorrhage. The authors recommend routine real-time ultrasound brain-scans at one month of age for all infants with SEH-IVH, and continued close observation with serial head-measurements of those with enlarged ventricular systems at that time.

Rationale for Grading Intracranial Hemorrhage in Premature Infants

There is a high incidence of hemorrhage in the germinal matrix and ventricular system in premature infants. Existing systems of grading the extent of hemorrhage into germinal matrix and ventricles of premature babies have limitations. It is necessary to consider correlations of structure (neuroanatomy by ultrasound) with function (outcome of patient). It is suggested that a standardized worksheet for evaluation of cranial ultrasound usage in premature infants be adopted. Such a worksheet allows uniformity of data collection and permits a more efficient method for evaluating correlations of structure with function.

Complications of intracranial hemorrhage in premature infants. Ultrasound follow-up two to fifteen months after birth.

One hundred prematurely born infants were evaluated 2 to 15 months after birth with real-time ultrasound. Seventy of these had intracranial bleeding as demonstrated by ultrasound examination during the first days of life. Nine of 13 (69%) infants with single or multiple sites of hemorrhage but without intraventricular hemorrhage had normal ultrasound at the late follow-up, 3/13 (23%) had mild and only one (8%) severe ventricular dilatation. Fifteen of 57 (26%) infants with intraventricular hemorrhage had normal ventricles at follow-up ultrasound, 26/57 (46%) mild and 16/57 (28%) moderate or severe ventriculomegaly. Only 2 infants were shunted. Porencephalic cysts developed in 5 infants. The size of ventricles may either progress or regress after the early posthemorrhagic period. Real-time ultrasound is the modality of choice not only for the diagnosis of intracranial hemorrhage in premature infants but also for late follow-up examinations as long as the size of the fontanelle permits the performance of the examination.

Ventriculitis with neonatal bacterial meningitis: Identification by real-time ultrasound

9. Deonna T, Payot M, Probst A, and Prod'ham LS: Neonatal intracranial hemorrhage in premature infants, Pediatrics 56:1056, 1975. 10. Farwell JR, and Scott DT: Intracranial hemorrhage in premature infants: Population characteristics, CSF findings and factors related to outcome, Ann Neurol 4:186, 1978. I1. Fujimura M, Salisbury DM, Robinson RO, Howat P, Emerson PM, Keeling J, and Tizard JPM: Clinical events relating to intraventricular haemorrhage in the newborn, Arch Dis Child 54:409, 1979. i2. Volpe JJ: Intracranial haemorrhage in the newborn: Current understanding and dilemmas, Neurology 29:632, 1979. 13. Lazarra A, Ahmann PA, Dykes FD, Brann D, and Schwartz JF: Clinical predictability of intraventricular hemorrhage in preterm infants, Pediatrics 65:30, 1980. 14. Tsiantos A, Victorin L, Relier JP, Dyer N, Sundell J, Brill AB, and Stahlman M: Intracranial hemorrhage in the prematurely born infant. Timing of clots and evaluation of clinical signs and symptoms, J PEDIATR 85:854, 1974. 15. Krishnamoorthy KS, Fernandez RA, Momose KJ, DeLong GR, Moylan F, Todres ID, and Shannon DC: Evaluation of neonatal intracranial hemorrhage by computerized tomography, Pediatrics 59:165, 1977. 16. Saint-Anne Dargassies S: Neurological development in full-term and premature neonates, Amsterdam, 1977, Elsevier/North Holland/Excerpta Medica. 17. Prechtl H: The neurological examination of the full-term newborn infant, in Clinics in developmental medicine, No. 63, London, 1977, SIMP/Heinemann. 18. Prechtl H, and Beintema D: The neurological examination of the full-term newborn infant, in Clinics in developmental medicine, No. 12, London, 1964, SIMP/Heinemann. 19. Brazelton TB: Neonatal behaviour assessment scale, in Clinics in developmental medicine, No. 50, London, 1973, SIMP/Heinemann.

1428 APNEA OF PREMATURITY AND INTRACRANIAL HEMORRHAGE

The association of apnea of prematurity with intracranial hemorrhage (ICH) has long been suspected clinically. To test this relationship we studied 22 healthy preterm infants from the first hours of life. The birth weight range was 800 - 1680gms., gestational age range was 28 - 34 wks., and 5′ Apgar score range was 5 - 9. Respiration was monitored by impedance pneumography and continually recorded on pneumotachograph for the first 10 postnatal days. In addition, all infants underwent cranial real time ultrasound scanning 1 - 7 times. Apnea was defined as the cessation of respiration ≥ 15 seconds. Infectious, metabolic, obstructive and thermoregulatory causes for apnea were ruled out. The infants were divided into 2 groups. Group A consisted of 11 infants with > 10 apneic episodes during the first 10 days. Four required assisted ventilation for severe apnea. The remaining seven had a range of 13 - 252 apneic episodes. Group B consisted of 11 infants who had ≤ 10 apneic episodes during the first 10 days. Results: In group A, 10 of the 11 infants demonstrated ICH in contrast to group B where only 1 of the 11 infants showed ICH (P < 0.01). There was no difference between the groups in terms of birth weight, gestational age and Apgar score. Three of the four infants who required assisted ventilation had extensive ICH. In two of these the ICH was found prior to being placed on the respirator. The results confirm the strong association between apnea and ICH in preterm infants. Further studies are necessary to define the causal relationship between ICH and apnea of prematurity. – Supported in part by Ariel Kaare Rosholt Weathers-Lowin Medical Research Foundation.

Treatment of neonatal hypoglycemia with minibolus and intravenous glucose infusion

nial hemorrhage in newborn infants. J PEDIAIR 94:800, 1979. 3. Deonn a T, Payor M, Probst A, and Prod'hom L-S: Neonatal intracranial hemorrhage in premature infants, Pediatrics 56:1056, 1975. 4. Diebler C, and Aicardi J: Hemorrhagie meningee du nourrisson et tiypoglycorachie, Arch Fr Pediatr 30:1031, 1973. 5. Dubynsky O, Vannucci R, and Maisels M J: Post-hemorrhagic encephalopathy in premature infants (abstr), Pediatr Res 12:551/1123, 1979. 6. Mantovani JF, Pasternak JF, Mathew OP, et al: Treatment of newborn intraventricular hemorrhage by repeated lumbar puncture (abstr), Ann Neurol 6:173, 1979. 7. Marbach EP, and Well MH: Rapid enzymatic measurement of blood lactate and pyruvate: use and significance of metaphosphoric acid as a common precipitant, Clin Chem 13:314, 1967. 8. Fujishima M, Sugi T, Choki J, et al: Cerebrospinal fluid and arterial lactate, pyruvate and acid base balance in patients with intracranial hemorrhages, Stroke 6:707, 1975.

Early Increase in Intracranial Pressure in Preterm Infants

Noninvasive measurement of intracranial pressure is now available via the anterior fontanel in newborn infants. We measured intracranial pressure during the first week of life in 18 preterm infants and found a statistically significant increase from birth to age 24 hours and a significant decrease by 48 hours (13.8 vs. 24.4 vs. 14.3 cm H2O). This did not seem to be the result of postnatal head shrinkage. There were no other apparent correlations. We suspect that hypoxia may play an important role in the etiology of increased intracranial pressure. We believe that these findings may have important implications for intracranial hemorrhage in preterm infants.

Comment on Intracranial Bleeding in Infants

To the Editor: We read with interest the article by Deonna et al. entitled “Neonatal Intracranial Hemorrhage in Premature Infants,” reporting on 11 cases(Pediatrics 56:1056, December 1975). We have recently summarized the data on six similar infants in the neonatal intensive care unit at Madison, Wisconsin,and feel it is important to supplement the article of Deonna et al. For better comparison with results of other newborn units, it would have been helpful if

Hydrocephalus Secondary to Intracranial Hemorrhage in Premature Infants

Premature (low birth weight) infants are particularly susceptible to intracranial hemorrhage. This frequently arises from the subependymal area and may dissect into the brain or into the ventricles. If the infant survives, hydrocephalus is a frequent sequela. Because of major improvements in the care of premature infants in recent years and the proliferation of intensive care nurseries, increasing numbers of low birth weight infants are surviving and developing hydrocephalus. Seven cases are described of infants who developed hydrocephalus following intracranial bleeding. Initially, ventricular and lumbar punctures were done to attempt to control head growth but this was unsuccessful. Two were treated with temporary external ventriculostomy which did not permanently control the hydrocephalus. Definitive treatment included ventriculo-atrial shunts using an expandable 'telescopic' cardiac catheter in two and ventriculoperitoneal shunts in five. The pathogenesis and management of the condition are discussed.

Neonatal Intracranial Hemorrhage in Premature Infants

Since the advent of modern methods of neonatal care, intracranial hemorrhage in premature infants, which is usually intraventricular, is probably not as uniformly fatal as generally admitted and the survivors are likely to develop post-hemorrhagic hydrocephalus. This paper is a retrospective study of 11 premature babies born between 1968 and 1972 and diagnosed as having hydrocephalus secondary to neonatal intracranial hemorrhage. Nine of these are still alive and two have died, one at 3 and one at 17 months of age. Eight underwent permanant surgical drainage of hydrocephalus. The perinatal history, laboratory data, clinical evolution, and neurological outcome were studied. Two groups of infants were identified; those with signs of acute neurological deterioration in the neonatal period who had the most severe neurological sequellae (in four cases, periventricular lesions in addition to hydrocephalus were seen on the air study and in one case confirmed at autopsy) and those showing no obvious neurological signs in the neonatal period. Of this latter group, two appear to be developing normally. The therapeutic implications of the findings are discussed.