Francesc Botet

Intrauterine restriction (IUGR)

Abstract Perinatal mortality and morbidity is markedly increased in intrauterine growth restricted (IUGR) fetuses. Prenatal identification of IUGR is the first step in clinical management. For that purpose a uniform definition and criteria are required. The etiology of IUGR is multifactorial and whenever possible it should be assessed. When the cause is of placental origin, it is possible to identify the affected fetuses. The major complication is chronic fetal hypoxemia. By monitoring the changes of fetal vital functions it is thus possible to improve both management and outcome. The timing of delivery is crucial but the optimal management scheme has not yet been identified. When IUGR is identified at very early gestational ages, serial assessments of the risk of continuing the in utero fetal life under adverse conditions versus the risks of the prematurity should be performed. Delivery of IUGR fetuses should take place in centers where appropriate neonatal assistance can be provided. Careful monitoring of the IUGR fetus during labor is crucial as the IUGR fetus can quickly decompensate once uterine contractions have started.

Decreased Regional Brain Volume and Cognitive Impairment in Preterm Children at Low Risk

OBJECTIVE: To investigate whether preterm children with low risk for neurodevelopmental deficits show long-term changes in gray matter (GM) and white matter (WM) volumes compared with term children and to relate these changes to cognitive outcome. METHODS: MRI was used to evaluate 20 preterm children who were determined to be at low risk for neurodevelopmental deficits and were born between 30 and 34 weeks’ gestational age without major neonatal morbidity or cerebral pathology in the neonatal period and 22 matched, term control subjects. Volumetric images were analyzed by means of voxel-based morphometry to identify regional cerebral alterations. Children also underwent cognitive and behavioral/emotional assessments. RESULTS: Preterm children showed global and regional GM volume reductions in several brain areas, including temporal and parietal lobes and concomitant WM volume reductions in the same areas, although only the left temporal regions achieved statistical significance. Global intellectual performance in the preterm group was significantly decreased compared with control subjects. Neither behavioral nor emotional problems were found in the preterm group. In the whole sample, we found a positive correlation between GM volume bilaterally in the middle temporal and in the postcentral gyri with IQ. Positive correlations were observed between GM and gestational age at birth in parietal and temporal cerebral regions and with WM in parietal regions. CONCLUSION: Preterm birth has an important impact on the neurodevelopmental and cognitive outcome of children at 9 years of age, being a risk factor for decreased regional cortical GM and WM even in preterm children with low risk for neurodevelopmental deficits.

Neurobehavior in Term, Small-for-Gestational Age Infants With Normal Placental Function

OBJECTIVE: The goal was to evaluate the neurobehavioral outcomes of term, small-for-gestational age (SGA) newborns with normal placental function. METHODS: A cohort of consecutive term SGA newborns with normal prenatal umbilical artery Doppler ultrasound findings was created and compared with a group of term infants with size appropriate for gestational age, who were sampled from our general neonatal population. Neonatal behavior was evaluated at corrected age of 40 ± 1 weeks with the Neonatal Behavioral Assessment Scale. The effect of the study group on each Neonatal Behavioral Assessment Scale area was adjusted, through multivariate analysis of covariance, for smoking during pregnancy, maternal BMI, socioeconomic level, onset of labor, mode of delivery, use of epidural anesthetic medication, gestational age at delivery, postnatal age (in days) at evaluation, and gender. RESULTS: A total of 202 newborns (102 SGA and 100 appropriate for gestational age) were included. All of the neurobehavioral areas studied were poorer in the SGA group, with significance for attention, habituation, motor, social-interactive, and regulation of state. The average mean differences in scores between the study groups were 0.77 (95% confidence interval: 0.38–1. 14) for attention, 0.64 (95% confidence interval: 0.13–1.14) for habituation, 0.52 (95% confidence interval: 0.31–0.74) for motor, 0.95 (95% confidence interval: 0.54–1.37) for social-interactive, and 0.68 (95% confidence interval: 0.23–1.13) for regulation of state. These differences remained significant after adjustment for potential confounders. CONCLUSION: Term SGA newborns with no signs of placental insufficiency had poorer neurobehavioral competencies, which suggests delayed neurologic maturation.

Influence on fetal growth of exposure to tobacco smoke during pregnancy

We analysed the effect of exposure to tobacco smoke during pregnancy on fetal growth parameters in 129 term newborns. Children were classified into four depending on exposure on the basis of a questionnaire completed by the mother. The results confirmed that tobacco smoking reduced weight, length, cranial and thoracic perimeters at birth when exposure was due to either active or passive smoking. Weight deficits of infants whose mothers smoked heavily (458 g) were higher than those whose mothers were exposed to passive smoking (192 g). We conclude that passive smoking is a very important variable and should be taken into account in any study of neonatal growth parameters.

Patterns of cerebral white matter damage and cognitive impairment in adolescents born very preterm.

There is increasing evidence about the presence of white matter damage in subjects with a history of premature birth, even in those classified as good outcome because of an apparently normal development. Although intellectual performance is within normal limits in premature children it is significantly decreased compared to paired controls. The purpose of this study was to investigate the relationship between a lower performance intelligence quotient and white matter damage in preterm adolescents. The sample comprised 44 adolescents (mean age ± S.D.: 14.4 ± 1.6 years) born before 32 weeks of gestational age and 43 term‐born adolescents (14.5 ± 2.1 years). Individual voxel‐based morphometry analyses demonstrated that 35/44 (80%) preterm subjects had white matter abnormalities. The centrum semiovale and the posterior periventricular regions were the most frequently affected areas. Correlation analysis showed that in preterms the performance intelligence quotient correlated with the whole‐brain white matter volume (r = 0.32; P = 0.036) but not with grey matter volume. Complementary analysis showed that low scores in the Digit Symbol subtest, a measure of processing speed, in the preterm group correlated with reductions in white matter concentration. These results suggest that white matter damage is highly common and that it persists until adolescence. Hence, diffuse white matter loss may be responsible for performance intelligence quotient and processing speed decrements in subjects with very preterm birth.

Differential effects of intrauterine growth restriction on brain structure and development in preterm infants: a magnetic resonance imaging study.

Previous evidence suggests that preterm newborns with intrauterine growth restriction (IUGR) have specific neurostructural and neurodevelopmental anomalies, but it is unknown whether these effects persist in early childhood. We studied a sample of 18 preterm IUGR, 15 preterm AGA - born between 26 and 34 weeks of gestational age (GA) - and 15 healthy born-term infants. Infants were scanned at 12 months corrected age (CA), in a 3T scanner, without sedation. Analyses were made by automated lobar volumetry and voxel-based morphometry (VBM). The neurodevelopmental outcome was assessed in all subjects at 18 months CA with the Bayley Scale for Infant and Toddler Development, third edition. IUGR infants had reduced relative volumes for the insular and temporal lobes. According to VBM, IUGR infants had bilateral reduced gray matter (GM) in the temporal, parietal, frontal, and insular regions compared with the other groups. IUGR infants had increased white matter (WM) in temporal regions compared to the AGA group and in frontal, parietal, occipital, and insular regions compared to the term group. They also showed decreased WM in the cerebellum and a non-significant trend in the hippocampus compared to term infants. IUGR infants had reduced neurodevelopmental scores, which were positively correlated with GM in various regions. These data suggest that the IUGR induces a distinct brain pattern of structural changes that persist at 1 year of life and are associated with specific developmental difficulties.

Hippocampal gray matter reduction associates with memory deficits in adolescents with history of prematurity

Using optimized voxel-based morphometry (VBM), we compared the relationship between hippocampal and thalamic gray matter loss and memory impairment in 22 adolescents with history of prematurity (HP) and 22 normal controls. We observed significant differences between groups in verbal learning and verbal recognition, but not in visual memory. VBM analysis showed significant left hippocampal and bilateral thalamic reductions in HP subjects. Using stereological methods, we also observed a reduction in hippocampal volume, with left posterior predominance. We found correlations between left hippocampal gray matter reductions (assessed by VBM) and verbal memory (learning and percentage of memory loss) in the premature group. The stereological analysis showed a correlation between verbal learning and the left posterior hippocampus. Our results suggest that left hippocampal tissue loss may be responsible for memory impairment and is probably related to the learning disabilities that HP subjects present during schooling.

Estimated weight centile as a predictor of perinatal outcome in small‐for‐gestational‐age pregnancies with normal fetal and maternal Doppler indices

To evaluate the risk of adverse perinatal outcome according to estimated fetal weight (EFW) in a cohort of term small‐for‐gestational‐age (SGA) pregnancies with normal umbilical, fetal middle cerebral and maternal uterine artery Doppler indices.

Neuropsychological long-term sequelae of perinatal asphyxia

Objective : To investigate the long-term neuropsychological consequences of perinatal asphyxia (PA). Methods : A group of adolescents were assessed with antecedents of mild ( n = 8) and moderate ( n = 20) PA, and a matched group of 28 healthy adolescents as a control group. Neuropsychological assessment included tests of memory, perceptual-motor skills, and frontal lobe functions, because these are areas of cognitive functioning susceptible to hypoxic conditions. Results : Subjects with moderate PA showed significant differences from the control group on tests related to delayed recall for both verbal and visual information, perceptual-motor speed, and tests assessing attention and executive functions. Conversely, subjects in the mild PA group exhibited scores which were similar to those of the control group in all the assessed variables. Conclusion : The present findings demonstrate that subtle but persistent neuropsychological deficits were observed in adolescents with antecedents of moderate PA, but not in those classified with mild asphyxia.

Neurobehavioral outcomes in preterm, growth‐restricted infants with and without prenatal advanced signs of brain‐sparing

To evaluate the neurobehavioral outcomes of preterm infants with intrauterine growth restriction (IUGR), with and without prenatal advanced brain‐sparing.