Biomarker epidemiology of cerebral palsy.
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Biomarkers↗
Biomedical subjects
Olaf Dammann
Publications and source records attributed to Olaf Dammann.
Inflammatory brain damage in preterm newborns--dry numbers, wet lab, and causal inferences.
Epidemiologic observations support the contention that infection, inflammation, and neonatal white matter damage (WMD) are associated. We also have documentation from multiple experimental models that infection/inflammation can damage developing white matter. Based on these observations in humans and animals, we offer causal inferences using widely accepted causal criteria and the multivariable model of causation. As much as we want to, however, we are reluctant to state unequivocally that inflammation causes WMD in humans born much before term. The main reason is that we lack convincing evidence that inflammation precedes WMD (temporal evidence). We also need more (and more detailed) observational studies clarifying the presumed infection --> inflammation --> WMD sequence before we can initiate intervention trials to reduce the risk of WMD.
Analysis of Variance↗
Preconditioning and the developing brain.
Preconditioning occurs when a subinjurious exposure renders the brain less vulnerable to a subsequent damaging exposure. In this essay, various models of preconditioning in the immature brain are discussed. Adenosine, excitatory amino acids, nitric oxide, hypoxia-inducible factor, ATP-sensitive K+ channels, caspases, heat shock proteins, inflammatory mediators and gene expression all seem to be involved in sensing, transducing and executing preconditioning resistance. Also reviewed in this essay is evidence that some subinjurious exposures render the brain more vulnerable to a subsequent damaging exposure. We believe that unraveling the mechanisms of how the developing brain becomes inherently resilient or vulnerable will offer important insights into the pathogenesis of injury. Preconditioning of the brain or induction of tolerance of the immune system might be utilized in the future to decrease CNS vulnerability and the occurrence of perinatal brain injury.
Animals↗
Antimicrobial resistance in Escherichia coli sepsis.
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Anti-Bacterial Agents↗
Impact of motor skills on cognitive test results in very-low-birthweight children.
Standardized tests that are frequently used to evaluate the cognitive development of very-low-birthweight children often appear to measure motor ability as well as cognitive skills. To estimate the impact of motor skills on individual test performance among very-low-birthweight children of kindergarten age, we employed factor analysis in a sample of 298 very-low-birthweight children that included severely disabled children. Using a test battery designed to measure concentration, language skills, overall cognitive development, visuomotor abilities, and memory, we identified two factors in each of three diagnostic subgroups: unimpaired children (n = 184), clumsy children (n = 56), and children with cerebral palsy (n = 33). Based on the pattern of factor loadings, we interpret the first factor as capturing language and overall cognitive abilities, whereas the second factor appears to capture motor abilities. Language skills explained 49% and motor abilities accounted for 16% of the overall variance of the individual test results. Among children with attention deficit (n = 25), a third factor emerged. In these children, we interpret the first factor as capturing language or cognitive skills, the second as representing visuomotor skills, and the third as a quantifier of the ability to concentrate. The test battery tested the same abilities in impaired and unimpaired children; however, these were not always the abilities that the battery aimed to test. Future studies need to evaluate whether factor scores only for cognitive but not motor abilities might be useful outcome variables.
Attention Deficit Disorder with Hyperactivity↗
Bronchopulmonary dysplasia is not associated with ultrasound-defined cerebral white matter damage in preterm newborns.
Bronchopulmonary dysplasia (BPD) and cerebral white matter damage (WMD) are neonatal disorders that occur most commonly in those who are born much before term. In a large multicenter database, we sought to determine whether the two disorders occur together more frequently than expected and whether BPD and other neonatal respiratory characteristics are more common among infants who develop ultrasound-defined WMD than among those who do not. In a sample of 904 infants who were born before the 30th week of gestation and survived until 36 wk postmenstrual age, we did not find a co-occurrence of BPD and WMD above what would be expected by chance. Confounding does not seem to account for this lack of association between WMD and BPD. In conclusion, our findings do not support the hypothesis that BPD contributes to the occurrence of sonographically defined WMD.
Brain Diseases↗
Maternal fever at birth and non-verbal intelligence at age 9 years in preterm infants.
To test the hypothesis that characteristics of perinatal infection are associated with long-term cognitive limitations among preterm infants, we analyzed data from 294 infants (142 females, 152 males) < or = 1500 g birthweight and <37 completed weeks of gestation who were examined at age 9 years. We identified 47 children (20 females, 27 males) who had a non-verbal Kaufman Assessment Battery for Children (K-ABC) scale standard value below 70, i.e. more than 2 SDs below the age-adjusted mean. The 247 children (122 females, 125 males) with a score > or = 70 served as control participants. Maternal nationality and education, and low gestational age were significantly associated with a K-ABC non-verbal standard value <70. Both neonatal brain damage (intraventricular hemorrhage) and long-term sequelae (cerebral palsy [CP], diagnosed at age 6 years) were significantly associated with a below-normal non-verbal K-ABC score. Maternal fever at birth was present in five cases (11%) and eight controls (3%; odds ratio 3.6, 95% confidence interval 1.1 to 11.4). Clinical chorioamnionitis and preterm labor and/or premature rupture of membranes (as opposed to toxemia and other initiators of preterm delivery) were also more common among cases than control participants. When adjusting for potential confounders such as gestational age, maternal education and nationality, and CP, the risk estimate for maternal fever remained unchanged (3.8, 0.97 to 14.6). We conclude that perinatal infection might indeed contribute to an increased risk for long-term cognitive deficits in preterm infants.
Child↗
Antenatal mycoplasma infection, the fetal inflammatory response and cerebral white matter damage in very-low-birthweight infants.
We address the question as to whether Ureaplasma urealyticum or Mycoplasma hominis, cultured from the placenta of very-low-birthweight (VLBW) infants, are associated with an increased risk of (a) fetal vasculitis and (b) ultrasonographic cerebral white matter echolucency. The sample consisted of 464 VLBW infants for whom (i) the surface of the chorion was cultured for U. urealyticum and M. hominis; (ii) the placenta was examined histologically; and (iii) a cranial ultrasound scan was obtained close to days 1, 7 or 21. Infants with echolucency were compared with controls in univariable and stratified analyses and in multivariable logistic regressions. Fifty-three per cent of placentas from infants with fetal vasculitis harboured U. urealyticum compared with 18% of controls (P </= 0.001). M. hominis was present in 14% of cases of fetal vasculitis and in 2% of controls (P </= 0.001). Among cases of echolucency, 22% had U. urealyticum compared with 30% of controls (P = 0.33), whereas 17% of these cases and 5% of controls had M. hominis (P = 0.08). Our findings support the hypothesis that U. urealyticum in the placenta of VLBW infants contributes to the fetal inflammatory response without contributing to white matter damage. Our finding that M. hominis in the placenta was associated with a not quite significant threefold risk increase for echolucency deserves further investigation.
Brain↗
Neurological sequelae in in-vitro fertilisation babies.
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Brain↗
Perinatal infection, fetal inflammatory response, white matter damage, and cognitive limitations in children born preterm.
Only sparse information is available about a possible association between antenatal infection outside the brain and subsequent cognitive limitations among preterm infants. Based on published studies, we provide a theoretical schema that links them via the fetal inflammatory response and neonatal white matter damage. We conclude that the relationship between antenatal infection and cognitive limitations deserves much further attention by researchers interested in the prevention of this undesirable outcome of prematurity.
Acute-Phase Reaction↗
Systemic hypotension and white-matter damage in preterm infants.
This study was designed to test the hypothesis that systemic hypotension during the first postnatal week increases the risk of ultrasonographic echolucency in the white matter of preterm infants (< or = 28 weeks' gestation) while adjusting for confounders. From a study base of 1607 very-low-birthweight neonates (500 to 1500 g), a subsample of 243 preterm infants (122 females; < or = 28 weeks' gestation) was selected for echolucency and data collection prospectively for the entire first postnatal week. Data analyses were performed separately for the first 24 hours of life, for the interval from the end of the first 24 hours to the end of the fourth postnatal day, and for days 5, 6, and 7. Systemic hypotension was defined as the mean arterial blood pressure in the lowest quartile for the infant's week of gestational age. Protocol cranial ultrasounds were those obtained closest to days 1, 7, and 21. A committee of sonologists classified the infants as having either echolucency (echolucency group) or not (control group). Systemic hypotension during the first week of life appeared to be associated with echolucency in univariable analyses but the association did not persist after adjustment for potential confounders. Detailed summaries of 13 previous studies, the majority of which did not show an association between systemic hypotension and white-matter damage, are presented. In sum, these results do not support the hypothesis that systemic hypotension contributes to echolucency among preterm infants.
Brain↗
Risk of cranial ultrasound abnormalities in very-low-birth-weight infants conceived with assisted reproductive techniques.
OBJECTIVE: To evaluate risks of cranial ultrasound abnormalities among very-low-birth-weight (VLBW) infants conceived with fertility therapy (ovulation induction only or with assisted reproductive techniques [ART]) and of multiple gestation pregnancies. STUDY DESIGN: The incidences of cranial ultrasound abnormalities in 1473 VLBW infants conceived with and without fertility therapy and born of multiple versus singleton pregnancies were compared, using logistic regression models. RESULTS: Infants conceived with ART were less likely to have intraventricular hemorrhage (IVH). Twins and triplets had risks of cranial ultrasound abnormalities similar to those of singletons. Twins and triplets conceived with ART were at lower risk of IVH. CONCLUSION: VLBW infants conceived with ART do not appear to be at increased risk of cranial ultrasound abnormalities. Likewise, twins and triplets were not at increased risk of these abnormalities.
Brain Damage, Chronic↗
Chorioamnionitis, mechanical ventilation, and postnatal sepsis as modulators of chronic lung disease in preterm infants.
OBJECTIVE: This case-control study of chronic lung disease (CLD) evaluated the hypothesis that chorioamnionitis promotes CLD and interacts with other risk factors for CLD, including mechanical ventilation and postnatal infection. STUDY DESIGN: We identified a population of 193 infants who met our case criteria for CLD whose birth weights were 7 days and culture-documented sepsis. In multivariable analyses, infants were at greatest risk for CLD when they had exposure to both chorioamnionitis and either mechanical ventilation >7 days (odds ratio, 3.2; 95% confidence interval, 0.9-11) or postnatal infection (odds ratio, 2.9; 95% confidence interval, 1.1-7.4). CONCLUSIONS: We conclude that prolonged mechanical ventilation or postnatal infection increases the risk of CLD among surviving preterm infants and that these 2 factors interact with antenatal infection to further increase the risk of CLD.
Case-Control Studies↗
Association between maternal serum ionized magnesium levels at delivery and neonatal intraventricular hemorrhage.
OBJECTIVES: To determine whether magnesium sulfate (MgSO(4)) exposure is associated with a reduced risk for neonatal intraventricular hemorrhage (IVH). STUDY DESIGN: In a randomized, controlled trial, women in preterm labor were randomly assigned to receive MgSO(4), "other" tocolytic, or saline control. At delivery, we collected maternal antecubital and umbilical cord blood for determination of serum ionized magnesium levels. Neonatal IVH was diagnosed by cranial ultrasonogram. RESULTS: Among 144 infants, 24 were diagnosed with IVH. Using crude intention-to-treat analysis, we found that 18% (13/74) of survivors exposed after birth to MgSO(4) had IVH compared with 16% (11/70) of babies who were not exposed. Infants who had IVH were more likely to have been delivered by mothers with higher serum ionized magnesium (Mg) levels (0.75 vs 0.56 mmol/L) (P =.01). Using multivariable logistic regression, we confirmed that higher Mg levels are a significant predictor of neonatal IVH (adjusted odds ratio, 15.8; 95% CI, 1.4-175.0) even when adjusted for birth weight, gestational age, antenatal hemorrhage, and neonatal glucocorticoid exposure. CONCLUSIONS: In mothers with preterm labor, our data indicate that antenatal MgSO(4) exposure may be associated with an increased risk for IVH among their newborns.
Adult↗