Prenatal magnesium sulfate exposure and risk of cerebral palsy.
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Cerebral Palsy↗
Biomedical subjects
A Leviton
Publications and source records attributed to A Leviton.
Frequency of neuropathological abnormalities in very low birth weight infants.
The occurrences of histologic changes in the central nervous system of very low birth weight infants (500 to 1500 grams) according to gestational age and postnatal age are incompletely reported. In order to better understand the abnormalities present in this patient population, the brains of 67 very low birth weight infants who died after having had at least one cranial ultrasound scan were studied. More than half the infants were born at gestational ages of 24 to 26 weeks, and only 28% died within 24 hours (h) of birth. The slides of the brains of all 67 infants were reviewed simultaneously by 3 neuropathologists who had to agree on the presence and/or absence of each histologic characteristic. Among infants who died within 24 h of birth, fully one quarter had parenchymal hemorrhage, 42% had petechial hemorrhages in the white matter, and more than 20% had hypertrophic astrocytes. These data indicate that in utero, prepartum, injury to the nervous system was common. Compared with infants who died before the sixth day, those who survived at least 6 days were twice as likely to have moderate/severe ventriculomegaly, rarefaction, amphophilic globules, hypertrophic astrocytes, macrophage foci, coagulative necrosis, and hemorrhagic necrosis than those who died before the 7th postnatal day. Parenchymal hemorrhage and moderate/severe ventriculomegaly decreased in frequency with increasing gestational age. On the other hand, the older the gestational age, the higher the likelihood of finding amphophilic globules, hypertrophic astrocytes, macrophage foci, and zones of coagulative necrosis upon neuropathologic examination. Our data indicate that several central nervous system abnormalities appear to increase with both older gestational age and older postnatal age for infants born weighing less than 1500 grams. We were unable, however, to determine the relative contribution of gestational age and postnatal age to the specific neuropathologic findings in this study.
Aging↗
Does prepregnancy bacterial vaginosis increase a mother's risk of having a preterm infant with cerebral palsy?
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Adult↗
Predictors of ventriculoperitoneal shunt among babies with intraventricular hemorrhage.
We aimed to identify medical care practices that influence the need for ventriculoperitoneal shunt among infants who develop intraventricular hemorrhage. We reviewed the medical records of 82 babies with ultrasonographically documented intraventricular hemorrhage. We compared the 10 babies who required a ventriculoperitoneal shunt to the 72 controls who had intraventricular hemorrhage, but did not require a ventriculoperitoneal shunt or die, prior to discharge. We considered maternal, perinatal, and neonatal risk factors as potential predictive variables. Maternal preeclampsia, prenatal steroids, and cesarean delivery were associated with a reduced risk of shunt. Patients who did require a shunt were more likely than their nonshunted peers to be treated with dopamine, to receive greater volumes of total intravenous fluid, largely as albumin and red blood cells, and to have a higher incidence of acidosis, patent ductus arteriosus and systolic hypertension. Previously identified antecedents and correlates of intraventricular hemorrhage appear also to be the antecedents and correlates of progression to ventriculoperitoneal shunt among infants with intraventricular hemorrhage. These findings are consistent with the possibility that prenatal and postnatal care practices influence the risk for ventriculoperitoneal shunt among babies with intraventricular hemorrhage. This offers the promise that changes in obstetric and neonatal care will reduce the need for ventriculoperitoneal shunt in very low birthweight infants.
Cerebral Hemorrhage↗
Maternal intrauterine infection, cytokines, and brain damage in the preterm newborn.
To evaluate the hypothesis that the proinflammatory cytokines IL-1, IL-6, and tumor necrosis factor-alpha might be the link between prenatal intrauterine infection (IUI) and neonatal brain damage, the authors review the relevant epidemiologic and cytokine literature. Maternal IUI appears to increase the risk of preterm delivery, which in turn is associated with an increased risk of intraventricular hemorrhage, neonatal white matter damage, and subsequent cerebral palsy. IL-1, IL-6, and TNF-alpha have been found associated with IUI, preterm birth, neonatal infections. and neonatal brain damage. Unifying models not only postulate the presence of cytokines in the three relevant maternal/fetal compartments (uterus, fetal circulation, and fetal brain) and the ability of the cytokines to cross boundaries (placenta and blood-brain barrier) between these compartments, but also postulate how proinflammatory cytokines might lead to IVH and neonatal white matter damage during prenatal maternal infection. Interrupting the proinflammatory cytokine cascade might prevent later disability in those born near the end of the second trimester.
Blood-Brain Barrier↗
Maternal receipt of magnesium sulfate does not seem to reduce the risk of neonatal white matter damage.
OBJECTIVE: To investigate whether in utero exposure to magnesium sulfate is associated with a lower incidence of cranial ultrasonographic abnormalities that predict cerebral palsy in infants who weigh less than 1501 g at birth. DESIGN: For a prospective study of the antecedents of cranial ultrasonographic abnormalities, we enrolled infants who weighed 500 to 1500 g when born at five institutions. Data were collected by interview of the mothers and review of medical records. Protocol cranial ultrasonograms were obtained as close as possible to postnatal days 1, 7, and 21. Abnormality on cranial ultrasound scans was determined by a consensus committee of three sonologists. RESULTS: Of the 1518 infants for whom we knew whether the mothers received magnesium sulfate, the first protocol cranial ultrasound scan was available for 1409 infants, the second for 1274 infants, and the third for 1050 infants. Forty-five percent of infants were exposed to magnesium sulfate before delivery. The major correlates of magnesium sulfate exposure were receipt of antenatal corticosteroids and a diagnosis of preeclampsia and/or pregnancy-induced hypertension. Maternal magnesium receipt was not associated with a reduced incidence of hypoechoic or hyperechoic images of white matter parenchyma, intraventricular hemorrhage, or ventriculomegaly, even when the sample was stratified by each of six potential confounders. When adjustment was made for gestational age, a measure of birth weight for gestational age, antenatal corticosteroid exposure, preeclampsia and pregnancy-induced hypertension, route of delivery, and the occurrence of any labor, the risk ratios for each cranial ultrasonographic abnormality associated with magnesium sulfate exposure hovered close to 1. CONCLUSION: Maternal receipt of magnesium sulfate does not seem to be associated with an appreciably reduced risk of cranial ultrasonographically defined neonatal white matter damage, intraventricular hemorrhage, or ventriculomegaly.
Adrenal Cortex Hormones↗
Thyroxine values from newborn screening of 919 infants born before 29 weeks' gestation.
OBJECTIVES: Severe transient hypothyroxinemia in premature infants is associated with cerebral palsy and mental retardation: this study assessed its prevalence in very premature infants. METHODS: Congenital hypothyroidism screening programs in three states provided thyroxine values for 919 newborn infants younger than 29 weeks who were enrolled in a multicenter study. RESULTS: Thyroxine values were lower than 4.0 micrograms/dL in 21% of survivors and increased each week by 0.6 microgram/dL (95% confidence interval [CI] = 0.4, 0.7). At tests done 1 to 2 days after birth, levels were 2.5 micrograms/dL higher (95% CI = 1.8, 3.3) than at tests done at 8 to 14 days. In New York, levels were 1.0 microgram/dL higher (95% CI = 0.3, 1.6) than elsewhere. The levels of infants who died were 1.3 micrograms/dL lower (95% CI = 0.6, 2.0) than those of survivors. CONCLUSIONS: Severe transient hypothyroxinemia is common in very premature infants and deserves further study.
Gestational Age↗
Duration of transient hyperechoic images of white matter in very-low-birthweight infants: a proposed classification.
To enhance the comparability of research results, a uniform terminology is proposed for the description of the duration of transient hyperechoic images of white matter seen on cranial ultrasound scans of very-low-birthweight infants. The term 'flare' should be restricted to any hyperechoic image that resolves completely without any abnormality in its place. A flare should be termed 'brief' if it resolves within 6 days of its appearance, 'intermediate' if it disappears between 7 and 13 days after onset, and 'prolonged' if it disappears on day 14 or later.
Brain Diseases↗
Re: Effects of caffeine consumption on delayed conception.
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Caffeine↗
Maternal non-phenylketonuric mild hyperphenylalaninemia.
Unlike maternal phenylketonuria (PKU) which produces severe birth defects when untreated during pregnancy, maternal non-PKU mild hyperphenylalaninemia (MHP) has a less severe impact but whether it is benign or may have long-term consequences for offspring has been unclear. From an international survey of maternal MHP we obtained information about 86 mothers (blood phenylalanine (Phe) 150-720 mumol/l), their 219 untreated pregnancies and 173 offspring. Spontaneous fetal loss and congenital anomalies were no more frequent than normally expected. Median Z-scores for birth length and birth head circumference and offspring IQ (100), however, were significantly lower for maternal Phe > 400 mumol/l than for maternal Phe < 400 mumol/l, in which the median offspring IQ was 108. Data on maternal MHP from the prospective Maternal PKU Collaborative Study (MPKUCS) are as yet incomplete but seem to be conforming to the general pattern of the international survey. We conclude that maternal blood Phe levels above 400 mumol/l in maternal MHP are associated with lower birth measurements and slightly lower offspring IQ. It would seem that dietary intervention to lower the maternal Phe levels to below 400 mumol/l might be indicated in maternal MHP pregnancies with the higher blood Phe levels.
Adult↗
Ureaplasma urealyticum infection of the placenta in pregnancies that ended prematurely.
OBJECTIVE: To investigate the relationship between Ureaplasma urealyticum infection of the placenta and premature onset of labor. METHODS: We studied 647 pregnancies that resulted in the live birth of an infant weighing less than 1501 g. The chorionic surface of the placenta was cultured for U urealyticum, Mycoplasma hominis, and group B streptococci. RESULTS: The rate of ureaplasma isolation increased with increasing interval between rupture of membranes and delivery. When analyses were limited to the 96 singleton pregnancies that ended within 1 hour of rupture of membranes and before the 29th week of gestation, U urealyticum was prominently associated with an increased risk of premature onset of labor (P = .008 unadjusted, and P = .05 when adjustment was made for all potential confounders). Ureaplasma infection rate was lowest in pregnancies terminated because of severe maternal preeclampsia or progressive fetal growth restriction. CONCLUSION: Ureaplasma urealyticum infection is associated with premature onset of labor and with increasing duration of time between rupture of membranes and delivery. Eradication of ureaplasmas from the urogenital tract of women and their partners, ideally before conception, should be considered.
Adult↗
Ventriculomegaly, delayed myelination, white matter hypoplasia, and "periventricular" leukomalacia: how are they related?
Preterm infants, including some who have sustained intracranial hemorrhage, appear to be at increased risk of lateral ventricular enlargement. Although some occurrences might be due to an impairment of cerebrospinal fluid flow or absorption, many instances of ventriculomegaly without accompanying macrocephaly reflect diffuse white matter damage resulting in diminished (i.e., hypoplastic) white matter or an inadequate density of axons. Perinatally acquired widespread white matter damage is sometimes associated with the focal white matter necrosis. We hypothesize that in some infants both ventriculomegaly and delayed myelination are consequences of disturbances to myelinogenesis that result from an impairment of cells destined to become oligodendroglia or of disturbances to rapidly growing axons. The vulnerability of developing white matter in preterm newborns might, in part, reflect the diminished availability of growth/ survival factors, or a vulnerability to toxins or physiologic perturbations. Awareness that some ventriculomegaly reflects widely distributed white matter damage should prevent overtreatment of what might appear to be hydrocephalus, but is not due to impaired cerebrospinal fluid dynamics. Increased understanding of the phenomena leading to ventriculomegaly related to paucity of white matter should lead to successful efforts to prevent white matter damage in preterm newborns.
Axons↗
Coffee consumption and residual confounding.
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Coffee↗
Survival of children with infratentorial neuroglial tumors. The Childhood Brain Tumor Consortium.
OBJECTIVE: The goal of this study is the improvement of the prognostic information associated with conventional diagnoses. Our previous factor analysis of 26 reliably identified histological features in infratentorial childhood neuroglial tumors yielded five interpretable, uncorrelated, quantitative histological factors that we named spongy, fibrillary, proliferative, nuclear, and ring. Five quantitative scores, one for each of the five factors, provide an objective method for quantifying the histological heterogeneity of a tumor. The scores, alone or in conjunction with conventional diagnoses, identify groups of histologically homogeneous tumors. METHODS: Multivariate Cox proportional hazards models were developed to assess the contribution of each factor to survival prognosis, after allowing patient-specific demographic and clinical data in the models as covariates. Hazard ratios, estimated for each statistically significant factor and covariate in the multivariate model, provide the basis for the determination of the prognosis. The hazard ratio is the ratio of the hazard function for subjects with an attribute, e.g., an age of 10 years, to the hazard function for subjects who have some chosen baseline attribute, e.g., an age of 1 year. The important criterion of this ratio is beta, a statistic estimated from the survival data in the Childhood Brain Tumor Consortium database of infratentorial neuroglial tumors. Kaplan-Meier survival curves were used to investigate differences in the survival of factor-determined subgroups of patients with various diagnoses. RESULTS: An increased likelihood of survival is associated with older age, more tumor removal, more recent decade of surgical intervention, and high spongy and fibrillary factor scores. A decreased likelihood of survival is associated with high nuclear, proliferative, and ring factor scores. Gender, location within the infratentorial compartment, and subsequent treatment did not add prognostic information. For certain subgroups of astrocytoma and for ependymoma and medulloblastoma, factors are important in predicting survival with greater accuracy. CONCLUSION: Factor scores provide clinically useful quantitative estimates of survival probability that are more specific and accurate than the general estimates based on the conventional diagnosis alone.
Adolescent↗
Persistent pulmonary hypertension of the newborn and smoking and aspirin and nonsteroidal antiinflammatory drug consumption during pregnancy.
OBJECTIVE: Prenatal causation of persistent pulmonary hypertension of the newborn (PPHB) is suggested by a specific pattern of pulmonary vascular remodeling observed immediately after birth in some infants with fatal PPHN. The goal of this study was to determine whether PPHN is associated with fetal exposure to: (1) tobacco and marijuana smoking (ie, contributors to fetal hypoxemia), (2) consumption of aspirin and other nonsteroidal antiinflammatory drugs (ie, inhibitors of prostaglandin synthesis), and (3) cocaine use (ie, a contributor to vasospasm). DESIGN: Case-control interview study. SETTING: Two Harvard-affiliated newborn intensive care units. PARTICIPANTS: Mothers of case infants who had PPHN or who met criteria for the referent group. INTERVENTIONS: During July 1985 through April 1989, we interviewed mothers of 103 infants with PPHN and 298 control infants. Because of potential selection bias that might result from recruiting only inborn control infants even though two-thirds of cases were outborn, separate analyses compared the 103 total and 35 inborn infants with PPHN with the 298 inborn control infants. Multivariate analyses were used to adjust for potential confounding factors, including maternal education and Medicaid health insurance (ie, two markers of socioeconomic status), other antenatal factors found to be associated with PPHN (ie, maternal urinary tract infection and diabetes mellitus), and the infant's sex. MAIN OUTCOME MEASURES: Self-reported use or consumption of tobacco, marijuana, cocaine, aspirin, and other nonsteroidal antiinflammatory drugs during pregnancy. RESULTS: The adjusted odds ratios (and 95% confidence intervals) for maternal pregnancy exposures to the factors of principal interest among the total study population were: aspirin, 4.9 (1.6-15.3); and nonsteroidal antiinflammatory drugs, 6.2 (1.8-21.8); for the inborn group they were aspirin, 9.6 (2.4-39.0); and nonsteroidal antiinflammatory drugs, 17.5 (4.3-71.6). Although the association between tobacco smoking during pregnancy and PPHN was elevated in univariate analyses, with odds ratios (and 95% confidence intervals) of 2.0 (1.2-3.4) and 1.3 (0.6-3.3) for total and inborn populations, respectively, the relationship was not significant after adjustment for all other factors in the final logistic regression model. Acknowledged illicit drug use was too infrequent (3.2%) to evaluate. CONCLUSION: Maternal consumption of nonsteroidal antiinflammatory drugs and aspirin during pregnancy or the reasons these drugs were ingested seem to contribute to an increased risk of PPHN.
Adult↗
Hypocarbia before surfactant therapy appears to increase bronchopulmonary dysplasia risk in infants with respiratory distress syndrome.
OBJECTIVE: To determine to what extent the risk of bronchopulmonary dysplasia is affected by ventilatory management before the first dose of rescue artificial surfactant. STUDY DESIGN: Retrospective cohort study. SUBJECTS: One hundred eighty-eight low-birth-weight infants (< or = 1700 g) who received artificial surfactant therapy for respiratory distress syndrome and who were alive at 36 weeks of gestational age. OUTCOME: Bronchopulmonary dysplasia was defined by a need for supplemental oxygen to maintain an arterial saturation of 92% or more at 36 weeks of gestational age. RESULTS: Thirty-seven percent (70/188) of the cohort met study criteria for bronchopulmonary dysplasia. Early determinants significantly associated with bronchopulmonary dysplasia (given as odds ratio, 95% confidence interval) in the most parsimonious backward stepwise logistic regression model included the following: birth weight of 1000 g or less (5.1, 2.4 to 10.7), cesarean birth because of fetal distress (4.4, 1.7 to 11.4), ventilatory efficiency index of 0.15 or less before surfactant therapy (3.1, 1.4 to 6.8), arterial-alveolar oxygen ratio of 0.15 or less before surfactant therapy (2.2, 1.01 to 4.6), and a low arterial PCO2 (< or = 29 vs > or = 40 mm Hg, 5.6, 2.0 to 15.6; 30 to 39 vs > or = 40 mm Hg, 3.3, 1.3 to 8.3). The inverse relationship between hypocarbia and bronchopulmonary dysplasia persisted even in stratified analyses limited to infants with measures of cardiovascular or respiratory illness that suggested less severe manifestations of disease. CONCLUSIONS: Ventilatory management before rescue treatment with artificial surfactant therapy that result in hypocarbia may increase the risk of bronchopulmonary dysplasia. These findings suggest that early ventilatory management should not only provide adequate oxygenation but also limit hyperventilation.
Blood Gas Analysis↗
Effect of maternal glucocorticoid exposure on risk of severe intraventricular hemorrhage in surfactant-treated preterm infants.
OBJECTIVE: To determine whether the reduced risk of severe intraventricular hemorrhage (SIVH) that follows antenatal maternal glucocorticoid (AMG) receipt is mediated by an AMG effect on blood pressure or improved respiratory function in infants who receive artificial surfactant as rescue therapy. DESIGN: Retrospective cohort study. SETTING: Two level III neonatal intensive care units, Boston, Mass. PARTICIPANTS: Two hundred twenty-five infants < or = 32 weeks of gestational age and < or = 1.7 kg birth weight, treated with surfactant. MAIN FINDINGS: SIVH occurred in 10% (10/102) of infants who were exposed to AMG, compared with 23% (25/111) of infants not exposed (odds ratio, 0.4; 95% confidence interval, 0.2 to 0.8). Hypotension and need for colloid or dopamine were associated with both SIVH and the absence of AMG exposure (p < or = 0.03). Logistic regression models of SIVH risk and AMG exposure, with adjustment for antenatal potential confounders, were altered by the addition of measures of hypotension. Most clinical measures of pulmonary function, both before and after surfactant receipt, were not associated with reduced risk of SIVH and did not appear to account for the increased risk of SIVH in babies not exposed to AMG. CONCLUSION: The reduced risk of SIVH in preterm newborn infants whose mothers received AMG was associated with normal blood pressures. The association between AMG and SIVH was not consistently enhanced by respiratory function improvement after surfactant therapy.
Cerebral Hemorrhage↗
Models of delayed recovery.
After a biologic insult has impaired function of the developing central nervous system, recovery may not become apparent for years. Probability models adopted from the carcinogenesis, developmental neurobiology, learning decay, and stochastic process literatures are presented so that assumptions about apparent delays in the recovery process can be tested with data from longitudinal studies after a temporally circumscribed adverse event/exposure. This process of evaluating multiple models is exemplified with one data set. Nonlinear models of recovery are important because some children with early deficits first show improvement months to years later.
Brain↗