Grwptwr Jourmd of Obstetrics & Gynecology und Reproductit~r Biology, 36 ( 1992) 7% 77 1‘8lYY2 Elsrvicr Science Publishers B.V. All rights reserved 0028.2243/Y2/SOS.O0
Survival and long-term morbidity in preterm infants with and without a clinical diagnosis of periventricular, intraventricular hemorrhage Peter Jakobi ‘, Amir Weissman ‘, Etan Z. Zimmer a and Shraga Blazer ” llc~prtrtwwrrt of Ohstrtrics und C~wrcolo~y ‘B’ and ” Neorrutul Int~wsic‘c Cure Uttit. Rumhum Mediul C‘~WCI. Fuculty of Medicine. Huifu. I.trarl Accepted
I I June
Summary The prognosis of clinically diagnosed periventricular, intraventricular hemorrhage on the survival and long-term outcome of 169 infants delivered at 24 to 30 weeks gestation who survived more than 48 hours was evaluated. Periventricular, intraventricular hemorrhage was confirmed by ultrasound in 37.9% of the survivors. In this group the survival rate was 64% and the major handicap rate was 14.6%. In contrast, the survival of infants who did not have a clinical diagnosis of periventricular, intraventricular hemorrhage was greater than 90% with a major handicap rate of only 3.2% (P < 0.0001and P < 0.03, respectively). Infants with clinical diagnosis of periventricular, intraventricular hemorrhage who were found to have grades l-2 by ultrasound had the same survival rate as those without a clinical diagnosis of periventricular, intraventricular hemorrhage (90.5%), while infants with grades 3-4 had a survival rate of only 51.2% (P < 0.01). We conclude, that preterm infants who survive longer than 48 hours and do not have a clinical suspicion of periventricular, intraventricular hemorrhage, have an excellent prognosis. In these circumstances brain sonography can be deferred without jeopardizing the infants’ health. Preterm
Introduction Despite improved survival for premature infants delivered even at 23 to 25 weeks gestation, the incidence of periventricular, intraventricular hemorrhage (PIVH) and major neurodevelopmental handicaps later on in life remained virtually unchanged [l-5]. It has been previously re-
C’otnqmrrdrnce and Gynecology I\rarl.
/o: Dr. P. Jakobi, ‘B‘,
of Obstetrics Haifa
ported that 40% to 90% of infants of less than 32 weeks gestation or < 1500 g birthweight have PIVH, and that 10-200/c of the survivors of the neonatal intensive care units experience major neurodevelopmental handicaps [4,6,7]. PIVH has been reported as the single most important etiologic cause of handicaps in these survivors [4,8]. In the present study, we evaluated the significance of the presence or absence of clinically diagnosed PIVH on the survival and long-term outcome of preterm infants of 24 to 30 weeks gestation who survived more than 48 hours.
The case records of all infants delivered at 24 to 30 gestational weeks in the years 1982-1986 at the Rambam Medical Center were reviewed. Gestational age was based upon menstrual data, early pregnancy tests, bimanual palpation of the uterus and/or ultrasound examination in the first trimester. Results were usually confirmed by at least one midgestation ultrasonographic examination. Postnatal assessment of gestational age was determined by physical examination, Dubowitz scoring system (if the infants’ condition allowed), and according to the lens scoring . All parturients with suspected preterm delivery had an ultrasound examination performed at admission to confirm gestational age, presentation, estimated weight, and to preclude possible gross malformations which may influence management of delivery. Intrapartum management of all parturients included electronic fetal monitoring. A neonatological staff was present in each preterm delivery ready to perform resuscitation immediately following delivery. Our policy is to resuscitate every preterm infant born at > 24 weeks gestation, and all infants received maximal treatment until their death. Following delivery, a presumptive diagnosis of PIVH was made when clinical signs were present (e.g., hypotension, full anterior fontanelle, focal or generalized seizures, decreased muscular tone) accompanied with laboratory findings (drop of hematocrit, metabolic acidosis, bloody cerebrospinal fluid). In these cases an ultrasound
examination was performed to confirm the clinical diagnosis, usually not before 48 hours following delivery. During the study period ultrasound examination was not routinely performed in asymptomatic preterm babies. Grading of PIVH was according to Papile et al. [lo]. Newborns who survived were followed up in the pediatric clinic or in district infant welfare clinics. Infants who completed at least 2 years of follow-up were included in the long-term followup group. The classification of handicaps was in terms of definitive functional or neurologic defects, only the major ones were included in our follow-up report: cerebral palsy, blindness, neurosensory deafness or definitive retardation in carrying out ordinary activities corrected for age
[61. Statistical analysis was performed with the Chi-square test with the Yates correction or Fisher’s exact test as needed. Results
During the 5-year period, 237 infants of 24 to 30 weeks gestation without congenital anomalies incompatible with life, were evaluated. Excluded from the study were 68 infants who died within 48 hours of delivery, generally with multisystem organ failure. The study group consisted of the 169 infants who survived > 48 hours; in 64 (37.9%) a diagnosis of PIVH was suggested. The clinical diagnosis of PIVH was confirmed by ultrasound examination in all these newborns. All
Periventricular, Gestational age (weeks)
age and extent of bleeding
24-26 27-28 29-30
28 68 73
3 10 8
10.7 14.7 11.0
10 24 9
35.7 35.3 12.3
13 34 17
46.4 * 50.0 ** 23.3
* P < 0.05 compared to 29-30 weeks. * * P < 0.002 compared to 29-30 weeks.
to the grade of periventricular. in ultrasound-proven
cases and in asymp-
No clinical 10s
* P c 0.01.
the 136 neonates who survived were available for follow-up at the age of 2 years. Table I shows the incidence and grade of PIVH in the ultrasound proven cases according to gestational age. Infants of 29-30 weeks gestation had significantly less PIVH than infants of 27-28 weeks or 24-26 weeks. Table II shows the survival according to the extent of hemorrhage. Low grade of PIVH (grade I-2) was associated with a survival rate identical to infants without clinical evidence of PIVH (90.5%), while infants with severe hemorrhages (grades 3 and 4) had only 5 1.2% survival rate (P < 0.01 I. Table III shows survival and handicap rate of the infants according to gestational age and the presence of PIVH. There is a significant higher survival rate in the whole group of infants with-
out clinical diagnosis of PIVH compared to those with sonographically confirmed PIVH, although in the age group of 24 to 26 weeks it did not reach statistical significance. Similarly, major handicap rate was also significantly lower in infants without clinical PIVH. Six of the infants (14.6%) with PIVH developed a major handicap: three had cerebral palsy, one had sensorineural deafness and two were blind. In the group without clinical PIVH there were three infants (3.2%) with major handicaps: one with cerebral palsy and two with blindness. Even if the four cases of blindness in the two groups, which can not be directly attributed to the presence of PIVH are excluded from analysis, still the major handicap rate in the group with confirmed PIVH is 9.8% (4/41) compared to 1.1% (l/95) only in the group without clinical diagnosis of PIVH (P < 0.041. Discussion Despite the great improvements in neonatal care, PIVH continues to be one of the leading causes of neonatal mortality and morbidity. It is of interest that according to our results infants who survive the first 48 hours and have clinical signs of PIVH, but found to be of low grade (grades l-2), have a survival rate identical to infants who have no clinical signs of PIVH. Furthermore, it was encouraging to find out that in
Survival and handicap
Infants with confirmed
h4.0 * *
P < 0.02. w* P ‘. 0.0001. _ I’ < 0.03.
Infants without clinical PIVH
* P < 0.003.
age and the presence of perivcntricular.
14.6 + +
105) Handicapped .-__-_ ,I ‘; .7 20.0
90.5 * *
:J 3 ____.
the absence of clinical signs of PIVH, even in very preterm infants of 27-30 weeks gestation, the survival was more than 90% and the major handicap rate only 1.2%. Theoretically, it is possible that in this group, not been examined by an early sonography, there were cases of PIVH. However, according to the results of mortality and severe handicap rate, practically this has no clinical importance. This is clearly different from the outcome of the neonates with a confirmed severe PIVH. Of the 136 surviving infants, 9 had a major handicap. The antenatal and postnatal variables of the nine infants, which could potentially affect their outcome, were completely different, and there was no common denominator between them. The only common finding in these cases was severe RDS and extensive PIVH, four of them developed various degrees of hydrocephalus later. Ultrasound examination has proved to be a useful tool in defining the incidence, extent and evolution of PIVH , yet, the prognostic significance of the sonographic findings and the prediction of even major handicaps in these infants remains controversial [6,11,12]. We found that two thirds (6/9) of our infants with major handicaps had also a confirmed diagnosis of PIVH, but only one third (6/22) of the infants with severe sonographically documented PIVH, developed major handicaps later. Thus, the results of our study corroborate the difficulties in the prediction of sonographically documented PIVH on future handicaps in the affected infants. When PIVH is confirmed by ultrasound, grades 1-2 do not increase the infants’ risk for major handicaps [13,14]. As for minor handicaps the data is even more limited. In a recent report, although in small numbers, on the neurodevelopmental outcome of very low birth weight neonates (< 1500 g> at 5 to 6 years of age, it was found that even mild PIVH (grades l-2) may have an adverse effect on global performance of the affected neonates [151. In another study, low grades of PIVH were associated with a relatively high handicap rate, which was lower but not statistically significant from those with severe grades of PIVH .
Not in every place in the world where preterm infants are born, ultrasound facilities are readily available for routine sonographic examination of these infants. Therefore, it is important to point out that according to our results, if PIVH is not diagnosed clinically by the third day of life, when 90% of the PIVH appears , the expected survival rate is higher than 90% accompanied with a very low rate of severe neurodevelopmental impairment. In conclusion, we suggest that in the absence of immediate sonographic facilities, if the infant survives more than 48 hours and the neonatologist does not suspect PIVH on clinical grounds, the prognosis of these infants is excellent both for survival and for major handicap rate. In these circumstances, ultrasound examination is not mandatory or can be delayed. Conversely, when there is a clinical suspicion of PIVH, the prognosis of these infants is poorer both for survival and for severe morbidity, only if grades 3-4 are found by ultrasound.
References 1 Nwaesei CG, Young DC, Byrne JM et al. Preterm birth at 23 to 26 weeks’ gestation: Is active obstetric management justified? Am J Obstet Gynecol 1987;157:890-897. 2 Milligan JE, Shennan AT, Hoskins EM. Perinatal intensive care: Where and how to draw the line. Am J Obstet Gynecol 1984;148:499-503. 3 Yu VYH, Loke HL, Bajuk B, Szymonowicz W, Orgill AA, Astbury J. Prognosis for infants born at 23 to 28 weeks’ gestation. Br Med J 1986;293:1200-1203. 4 Ment LR, Duncan CC, Ehrenkranz RA. Intraventricular hemorrhage of the preterm neonate. Sem Perinatol 1987;11:132-141. 5 Morales WJ, Angel JL, O’Brian WF, Knuppel RA, Marsalisi F. The use of antenatal vitamin K in the prevention of early neonatal intraventricular hemorrhage. Am J Obstet Gynecol 1988;159:774-779. 6 Kitchen WH, Yu VYH, Orgill AA et al. Collaborative study of very-low-birth-weight infants. Correlation of handicap with risk factors. Am J Dis Child 1983;137:555559. 7 Volpe JJ. Intraventricular hemorrhage and brain injury in the premature infant: neuropathology and pathogenesis. Clin Perinatol 1989;16:361-386. 8 Shennan AT, Milligan JE, Hoskins EM. Perinatal factors associated with death or handicap in very preterm infants. Am J Obstet Gynecol1985;151:231-238.
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