ELSEVIER Early Human Development 47 (1997) 195-201

Clinical features of and cardiotocographic findings for premature infants with antenatal periventricular

leukomalacia

Takashi Ito”, Koji Kadowaki, Hiroyuki Takahashi, Naoki Nagata, Akira Makio, Naoki Terakawa

lkptrrtment of Obstettics and Gynecology, Tottori University School of Medicine, 5% I NishirnrrAi,

Yorzago 683, Japm

Received 17 October 1995; revised 26 April 1996; accepted 30 May 1996

Abstract

Objective: To clarify the clinical features of and cardiotocographic findings for premature infants with antenatal periventricular leukomalacia (PVL). Me&o&: Antenatal PVL was judged to be present if a cyst greater than 3 mm in largest diameter was detected in the periventricular region by the 14th day of life on cranial ultrasonography. The clinical features of and cardiotocographic findings for 12 premature infants with antenatal PVL born within I year were compared with those of 12 infants chosen as control group matched in gestational age at birth from the premature infants without antenatal PVL born within the study period. Results: Abnormalities of the umbilical cord such as coiling, excessive torsion and me&rane insertion were observed more frequently for infants with antenatal PVL (58.3%) than for control infants (16.7%) (P < 0.05). Frequent moderate variable deceleration on the fetal cardiogram was also observed more frequently for infants with antenatal PVL. (80.0%) than for control infants (27.3%) (P < 0.05). Conclusion: Abnormalities of the umbilical cord and frequent moderate variable deceleration on fetal cardiotocogram appear to be causes of antenatal PVL in premature infants. 0 1997 Elsevier Science Ireland Ltd. All rights reserved

Keywords: Periventricular leukomalacia; Cardiotocogram; Umbilical cord: Premature infants

*Corresponding author. Tel: + 81 859 348127; fax: + 81 859 348089

037%3782/97/$17.00 0 1997 Elsevier Science Ireland Ltd. All rights reserved PII SO378-3782(96)0177Y-3

196 T. Ito et al. I Early Human Development 47 (1997) 195-201

1. Introduction

Periventricular leukomalacia (PVL) is thought to be one of the most important causes of cerebral palsy in premature infants [1,2]. PVL develops during not only the postnatal but also the antenatal period. There are many reports available concerning the clinical features of postnatal PVL. However, relatively few studies have been made of the clinical features of antenatal PVL. We therefore performed a matched control study to clarify the clinical features and cardiotocographic findings associated with antenatal PVL in premature infants.

Cysts of the periventricular region in newborn infants are usually observed 14 days or more after acute brain ischemia [3-61. Therefore, the diagnostic criterion for antenatal PVL used in this study was detection of a cyst greater than 3 mm in largest diameter in the periventricular region by the 14th day after birth on cranial ultrasonography.

2. Material and methods

Cranial ultrasonography through the frontal fontanelle was performed at least three times per week on all 51 premature infants born in Tottori University Hospital between April 1992 and March 1993 using an Aloka SSD-125 with a ~-MHZ probe (Aloka Company, Tokyo, Japan). Antenatal PVL was judged to be present if a cyst greater than 3 mm in largest diameter was detected in the periventricular region by the 14th day of life (Fig. 1). A total of 12 infants were diagnosed with antenatal PVL. The neurological assessment was performed by a neuropediatrician. Six of these 12 infants showed spastic diplegia and one showed spastic hemiplegia at 1 year after birth. Convergent squint was observed in three babies.

Five infants developed without cerebral palsy. However, four infants out of five showed mild enlargement of posterior horn of lateral ventricle and mild decrease of white matter volume in periventricular region on computerized tomography at 6- 18 months old. One baby has not been examined by computerized tomography.

Twelve infants born at the nearest gestational age to each infant with antenatal PVL were chosen as a control group matched for gestational age from among 41 premature infants without antenatal PVL born within the study period. If there were two or more cases born at the same nearest gestational age, the infant born earlier within the study period was chosen as a control case. The clinical features and cardiotocographic findings recorded during the antepartum and intrapartum periods of the 12 infants with antenatal PVL were compared with those of the control group. The observer of cardiotocograms was blinded to the outcome of the fetuses.

Fetal bradycardia of less than 120 beats/min lasting more than 10 min, loss of variability less than 5 beats/min for more than 30 min, late decelerations that repeat more than three times, and severe variable deceleration lasting more than 60 s or with minimum heart rate less than 60 beats/min were considered to represent fetal distress. Moderate variable deceleration was observed in many preterm subjects. In this study, therefore, the appearance of three or more episodes within 10 min of relatively large

T. Ito et al. I Early Human Development 47 (1997) 19-Y-201

Fig. 1. Ultrasonogram on the 7th day of life in case 7. A cyst was observed in the right periventricular region.

variable deceleration lasting less than 60 s and with a minimum heart rate above 60 beats/mm was defined as frequent moderate variable deceleration (Fig. 2). The rates of appearance of fetal distress and frequent moderate variable deceleration in the two groups were compared. The umbilical cord abnormalities such as coiling, excessive torsion and membrane insertion were observed at birth. The definitions of coiling and excessive torsion in this study are cord coiling around the fetal neck or trunk once or more and twisting of the cord more than once per 2 cm.

Statistical analysis was performed with Chi square analysis and Fisher exact test. A P-value < 0.05 was considered to indicate statistical significance.

3. Results

Fifty-three infants were born prematurely during the study period and 12 (22.6% ) were diagnosed with antenatal PVL.

In 10 babies out of 12, the cysts were found in the first 2 days after birth and in the other two babies, the cysts were found on the fourth and 11th day. The cysts were detected on bilateral periventricular regions in eight babies. The diameter of the cyst ranged from 3.4 mm to 7.0 mm.

A summary of the clinical features of these 12 infants is shown in Table 1. Gestational age ranged from 28 to 36 weeks. Three babies were small for gestational age. Three babies had low Apgar scores of less than 6. Two babies had an umbilical

198 T. Ito et al. l Early Human Development 47 (1997) 195-201

Fig. 2. Frequent moderate variable deceleration in case 6. Moderate variable decelerations were observed more frequently than three times per 10 min.

artery blood pH < 7.20 at birth. Only one had an umbilical blood C-reactive protein (CRP) above 0.5. Five infants among them were diagnosed as respiratory distress syndrome (Cases 4, 5, 6, 8 and lo), and six infants required intubation for respiratory assist for 2-43 days (Cases 2, 3, 4, 5, 6 and 10) after birth. None had a severe

Table 1

Clinical features of infants with antenatal PVL

Case Sex Gestational age Birth Apgar score pH CRP Delivery

(weeks, days) weight (g) (at l/5 min) (mgldl) mode

1 M 36, 3 2022 7/8 1.29 0.1 V

2 F 30, 5 1400 9110 1.32 0.0 C

3 F 34, 0 916 (S) 8/9 7.26 0.0 C

4 M 34, 3 1328 (S) 819 7.10 0.0 C

5 F 36, 1 2476 9110 1.30 0.1 C

6 M 30, 1 1458 8/8 7.32 0.0 V

7 F 28, 1 616 (S) 617 7.41 0.0 C

8 F 31, 2 1692 415 7.36 0.0 V 9 M 30, 5 1792 4/l 7.36 0.0 C

10 M 30, 4 1622 819 7.32 0.0 V 11 M 33, 2 1566 718 7.17 0.0 C 12 F 31, 4 1974 l/6 7.20 0.1 C

pH, umbilical artery blood pH; CRP, CRP of umbilical vein blood; V, vaginal delivery; C, cesarean birth; S,

small for gestational age.

T. Ito et al. I Early Human Development 47 (1997) 195-201

Table 2 Cardiotocographic findings in premature infants with antenatal PVL

Case Fetal distress Frequent moderate variable deceleration

Antepartum period Intrapartum period

2

3 4

5

6 7

8 9

10 11

12

- i - LD,SVD +

LD,SVD LD,SVD +

LD,SVD LD,SVD,BR ?- - ND ._

- -

LOV -

- - c

- ND -

ND BR NA - BR t

LD, late deceleration; SVD, severe variable deceleration; BR, bradycardia; LOV, loss of variability; ND, not determined; NA, data not available for short recording time.

respiratory or cardiovascular accident that might cause postnatal PVL such as apnea or hypotension in the neonatal period. Cardiotocographic findings are shown in Table 2.

A comparison of clinical features for the two groups is shown in Table 3. The distributions of gestational age in the two groups were appropriately matched. There were no significant differences between the groups in birth weight, rate of multiple gestation, frequency of placenta previa, frequency of small for gestational age, or frequency of fetal infection with CRP above 0.5. Abnormalities of the umbilica,J cord such as coiling, excessive torsion and membrane insertion were observed more frequently for infants with antenatal PVL (58.3%) than for control infants (16.7%). The results of umbilical artery blood gas analysis are shown in Table 4. No significant differences were found between two groups in pH, Pco,, Po2, and the frequency of acidosis, hypercapnia, and hypoxia. The cardiotocographic findings are

Table 3

Clinical features of infants with antenatal PVL and control infants

Clinical features

Gestational age (weeks) 31.822.8 32.0+3.0 NS Birth weight (g) 1571’494 16062675 INS

Twin pregnancy 3112 (25.0%) I/ 12 (8.3%) NS

Placenta previa 2/12 (16.7%) o/ 12 (0.0%) NS SGA 3112 (25.0%) 3/ I2 (25.0%) NS

CRP in umbilical vein blood > 0.5 l/12 (8.3%) o/ 12 (0.0%) NS Umbilical abnormality 7/ 12 (58.3%) 2/l? (16.7%) i 0.05

Infants with

antenatal PVL (n = 12)

Control

infants (n = 12)

P-value

SGA, small for gestational age; CRP, C-reactive protein; NS, not significant. Data are presented as meanzstandard deviation or n (%).

200 T. Ito et al. I Early Human Development 47 (1997) 195-201

Table 4 Results of umbilical artery blood gas analysis in antenatal PVL and control infants

Results of gas analysis

PH Pco, (m@d

PO, (mm&) pH < 7.20 Pco, < 35 mmHg

Po,<lO mmHg

Infants with antenatal PVL (n = 12) Control infants (fl = 12) P-value

7.284kO.087 7.265t0.063 NS 49.2211.2 44.328.5 NS

15.9k5.9 15.6k7.1 NS

2/12 (16.7%) l/12 (8.3%) NS 1112 (8.3%) l/l2 (8.3%) NS

2/12 (16.7%) 3/12 (25.0%) NS

Data are presented as meankstandard deviation or n (%).

shown in Table 5. There were no significant differences between the groups in the rate of fetal distress in either the antepartum or intrapartum periods. Frequent moderate variable deceleration was observed for infants with antenatal PVL (72.7%) compared with control infants (27.3%).

4. Discussion

The high incidence of antenatal PVL in this study is thought to be due to the fact that there were many high risk cases such as maternal transport (18 cases, 35.3%), for preterm PROM, premature labor, or EPH gestosis or twin pregnancy (16 cases, 31.4%) in 51 premature infants of this study.

Some previous studies of the clinical features of antenatal PVL in premature infants are available. Placental vascular anastomoses in multiple pregnancy, funitis, purulent amniotic fluid [6], maternal haemorrhage due to placental abruption or placenta previa [4], and metabolic acidosis [7] have been reported to be clinical features associated with antenatal PVL. Cardiotocographic findings have suggested that fetal distress is the cause of PVL [4]. However, in the present study, no significant difference in the rate of fetal distress was found between infants with and without antenatal PVL.

Our findings suggest that abnormalities of the umbilical cord such as coiling, excessive torsion and membrane insertion and frequent moderate variable decelera- tion appear to be causes of antenatal PVL. It is not easy to judge cardiotocographic findings as the cause or result of antenatal PVL. Moderate variable deceleration usually indicates umbilical cord compression and not brain damage. Therefore, we

Table 5

Cardiotocographic findings in infants with antenatal PVL and control infants

Cardiotocographic findings Infants with antenatal PVL Control infants P-value

Fetal distress Antepartum 3/11 (27.3%) l/11 (9.1%) NS Intrapartum 5/ 10 (50.0%) 3/11 (27.3%) NS

Frequent moderate variable deceleration 8/12 (66.7%) 3/11 (27.3%) < 0.05

Data are presented as mean-tstandard deviation or n (%).

T. Ito et al. I Early Human Development 47 (1997) 19.5-201 20 !

consider moderate variable deceleration is related to the cause of antenatal PVL. Variable deceleration usually appears when abnormalities of the umbilical cord are present. Abnormalities of the umbilical cord should cause ischemia and then reperfusion in the fetal brain, which should result in delayed neuronal death [9]. This appears likely to be the pathogenesis of antenatal PVL in premature infants.

The periventricular region is perfused by the ventriculopetal branch and ven- triculofugal branch. These branches develop incompletely in premature infants. Therefore, the periventricular region should in premature infants relatively easily develop ischemia and subsequent injury [8]. Findings of brain damage following intermittent partial cord occlusion have been reported in animal experiments [IO]. These findings coincide with the results of this study.

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