Elsevier

Early Human Development

Volume 52, Issue 1, 28 August 1998, Pages 67-79
Early Human Development

Neurodevelopmental outcome at three years of age after fetal `brain-sparing'

https://doi.org/10.1016/S0378-3782(98)00004-8Get rights and content

Abstract

Intrauterine growth restriction (IUGR), occurring preterm, may be related to impaired neurodevelopmental outcome. We measured neurodevelopmental outcome (Hempel examination) at the age of three years in a cohort of infants born between 26 and 33 weeks in 1989. Fetuses were studied haemodynamically, using Doppler ultrasound. The ratio between the umbilical and the cerebral artery Pulsatility Index (U/C ratio) was calculated. This is a measure of redistribution of fetal blood preferentially to the brain and this may be a marker of fetal adaptation to placental insufficiency. Impaired fetal growth was also measured by the fetal growth ratio. Neonatal cranial ultrasound was performed to document intracranial haemorrhages and/or ischaemia. From the original cohort of 106 infants, 96 (91%) infants were examined at three years. After adjustment for obstetric variables, adverse Hempel outcome was related to neonatal cranial ultrasound abnormality and low head circumference at three years. Neither the U/C ratio nor fetal growth were independently associated with Hempel outcome. Fetal `brain-sparing' in IUGR appears to be a benign adaptive mechanism preventing severe brain damage.

Introduction

Intrauterine growth restriction (IUGR) is generally considered to be associated with an increased risk of neurological deficiency and a less optimal (psycho)neurological development 7, 25. In studies concerning neurodevelopmental outcome, IUGR is generally defined as being a birthweight below the 10th percentile for gestational age. An overall effect of IUGR on developmental outcome was not evident, although differences in certain subclassifications of neurodevelopmental outcome were found 16, 17. Recently, no influence of IUGR or even a reduced incidence [29]of major handicaps is reported in preterm IUGR infants compared to preterm infants with an appropriate birthweight at the age of 18–20 months [8]and at the age of three years [26]. In IUGR 3-year-old infants, a lower Developmental Quotient is reported [26], although other researchers have not confirmed these findings [29]. IUGR infants are reported as having more often minor handicaps and signs of impaired psychomotor function [29]. The absence of differences in neurodevelopmental outcome between IUGR and nongrowth restricted toddlers might possibly be explained by the contention that the effects of IUGR on neurodevelopmental outcome is only becoming evident in children of school age [16]. Although in low-birth-weight (IUGR) infants of 8–10 years of age, more functional limitations, behavioural problems and learning difficulties are found in low-birth-weight (IUGR) 13, 15, 21, 22, 25, the effects of IUGR on neurodevelopmental outcome are still being debated. In a group of term IUGR infants, excluding asphyxiated babies and controlled for socioeconomical differences, a follow-up study in adolescence showed no differences in neurodevelopment or cognitive and academic achievements [31].

Besides IUGR, the occurrence of perinatal intracranial haemorrhage (ICH) and/or cerebral ischaemia may also have a decisive impact on neurodevelopmental outcome. The availability of detailed neurosonography is important in order to be able to analyze determinants of neurodevelopmental outcome.

In animal models, in which intrauterine growth restriction (IUGR) was induced by placental insufficiency, a preferential perfusion of the central nervous system, maintaining an optimal O2 supply to the brain [18], was demonstrated [2]. The introduction of Doppler ultrasound in obstetrics made the demonstration of this redistribution phenomenon also possible in the human fetus [32]. A raised ratio between Umbilical Artery Pulsatility Index (PI) and middle Cerebral Artery PI (the U/C ratio) is indicative of the existence of this `brain-sparing' effect 32, 33. Recently we published the results of an observational study in which infants born preterm with a raised U/C ratio were compared to control preterm infants with a normal U/C ratio. Fetuses were classified as growth restricted or normally grown based on a raised or normal antenatal U/C ratio, respectively. At one year of age, no detrimental effects of fetal `brain-sparing' were found in neurological outcome [23]. The incidence of severe intracranial pathology, as seen by cranial ultrasound, was not different in neonates who showed antenatal signs of `brain-sparing', compared to neonates without these findings [24]. In the same group of infants, at the age of three years, we describe in the present report neurodevelopmental outcome, as defined by the Hempel examination using the U/C ratio and neonatal cranial ultrasound findings as important explaining variables.

Section snippets

Patients and methods

The 107 women included in the study were consecutively admitted in 1989 to the department of obstetrics during a ten month period because of threatening preterm delivery (<33 weeks of gestation). Pregnancies with known congenital or chromosomal abnormalities were excluded. Seventeen women had twin pregnancies and 2 women were pregnant with triplets. This resulted in a group of 128 fetuses in which antenatal Doppler studies were performed. Intrauterine fetal death occurred in 11 cases. Out of

Intracranial haemorrhages

Eight infants had a severe ICH in the first week after birth. These neonates had already shown signs of ICH during the first cranial ultrasound performed within one hour after birth. Two of the eight children also had signs of increased parenchymal echodensities: one had a mild form; the other had a severe periventricular echodensity. Two of the children with an ICH had an impressive intraparenchymal bleeding (IPH) each located at one hemispheric side and both occurring within 24 h after birth.

Discussion

The presence of fetal haemodynamic adaptation to uteroplacental insufficiency, expressed as the U/C ratio, was used to classify a fetus as growth restricted [23]. Using this classification, a more homogeneous study population can be formed. Nearly all follow up studies of IUGR infants have thus far relied exclusively on birthweight categories. The disadvantage of using birthweight percentiles is that infants who are small, but for other reasons than placenta insufficiency, are also included in

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