Neurodevelopmental outcome at three years of age after fetal `brain-sparing'
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
References (33)
- et al.
Distribution of the circulation in the normal and asphyxiated fetal primate
Am J Obstet Gynecol
(1970) - et al.
Prenatal and perinatal factors and cerebral palsy in very low-birth-weight infants
J Pediatr
(1996) - et al.
Body measurements, neurological and behavioral development in six-year-old children born preterm and/or small-for-gestational-age
Early Hum Dev
(1990) Neurological development during toddling age in normal children and children at risk of developmental disorders
Early Hum Dev
(1993)- et al.
School performance at nine years of age in very premature and very low-birth-weight infants: perinatal risk factors and predictors at five years of age
J Pediatr
(1994) - et al.
Association of intrauterine fetal growth retardation and learning deficits at age 9 to 11 years
Am J Obstet Gynecol
(1992) - et al.
Small-for-dates babies at the age of four years: health, handicap and developmental status
Early Hum Dev
(1983) - et al.
Children of deviant birthweight at the age of seven years: health, handicap, size and developmental status
Early Hum Dev
(1984) - et al.
Blood flow to fetal organs as a function of arterial oxygen content
Am J Obstet Gynecol
(1979) - et al.
Neurosonographic features of periventricular echodensities associated with cerebral palsy in preterm infants
J Pediatr
(1990)
Cognitive abilities and school performance of extremely low-birth-weight children and matched term control children at age 8 years: a regional study
J Pediatr
Comprehensive assessment of the health status of extremely low-birth-weight children at eight years of age: Comparison with a reference group
J Pediatr
The `brain-sparing' effect: Antenatal cerebral Doppler findings in relation to neurologic outcome in very preterm infants
Am J Obstet Gynecol
Growth and neurodevelopmental outcome of very low-birth-weight infants with intrauterine growth retardation: comparison with control subjects matched by birthweight and gestational age
J Pediatr
Neurodevelopmental, health, and children with birth weight less than 1001 grams
J Pediatr
Developmental outcome and follow up of the small for gestational age infant
Sem Perinat
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