Chronic Prenatal Exposure Research Articles

Fetal heart rate patterns and chronic exposure to antiepileptic drugs.

Fetal heart rate (FHR) characteristics of fetuses exposed and not exposed to antiepileptic drugs (AEDs) were studied. FHR is considered to reflect central nervous system (CNS) integrity. Three intervals during pregnancy were investigated: 20, 32, and 38 weeks. At 32 and 38 weeks, FHR was studied in relation to quiet (C1F) and active (C2F) sleep periods. For each tracing, a baseline was determined and accelerations and decelerations were identified. To assess FHR variability, the long-term irregularity, interval difference and absolute beat-to-beat indexes, and the bandwidth were calculated for 30-s intervals between accelerations and decelerations. No marked differences were noted between study and control groups concerning basal FHR and the occurrence of accelerations. For FHR derived from the fetal ECG, all indexes of FHR variability and the bandwidth were lower for the study group as compared with the control group, although the differences did not reach statistical significance. Our study shows that chronic prenatal exposure to AEDs does not seriously interfere with modulation of fetal heart rhythm by the CNS.

Postnatal Functional Analysis of Prenatal Exposure of Rats to 915 MHz Microwave Radiation

Thirty pregnant Wistar strain albino rats were used to determine the effects of chronic prenatal exposure to 915 MHz microwave radiation at a continuous wave power density level of 10 mW/cm2 on postnatal growth and neurobehavioral development. Eleven rats were irradiated in a fully characterized anechoic chamber from days 1 to 21 of gestation. Mean total exposure time was 6544 min. Nineteen rats were used as control animals. All animals delivered and raised their offspring (F1a) until weaning at 30 days of age Ten days later females were rebred and a standard teratologic evaluation was completed on the resultant F1b fetuses. Maternal brain, liver, kidneys, and ovaries were removed, weighed, examined, and fixed in formalin. The F1a (irradiated) neonates were given four perinatal reflex tests (surface righting, air righting, auditory startle, visual placing). One physiological parameter, eye opening, was also observed. Weekly weights were recorded throughout the study period. At 60 days of age the offspring were randomly given 3 of 6 tests (conditioned avoidance response, water T-maze, open field, activity wheel, forelimb hanging, swimming). At 90 days of age reproductive capability was evaluated and a standard teratologic analysis performed on the resultant F2 offspring. The brain, liver, kidneys, and gonads of all F1a offspring were removed, weighed, examined, and fixed in formalin. No significant morphologic or neurobehavioral alterations were observed due to chronic prenatal exposure to 915 MHz microwave radiation at a continuous wave power density level of 10 mW/cm2.

Results of prenatal alcohol exposure on the dimensions and binucleation of cardiac myocytes in neonatal and weanling rats

Sprague-Dawley rats were exposed to ethyl alcohol in utero. The effect of chronic prenatal exposure was examined by giving mature females alcohol in isocaloric liquid diets which served as the sole source of liquid and caloric intake before mating and throughout gestation. Controls consisted of females maintained on laboratory chow or an isocaloric liquid diet minus alcohol before and during gestation. The offspring were sacrificed at 21 days of age (weanlings) and the hearts dissociated enzymatically to give purified cardiac myocytes. The effects of daily acute prenatal alcohol exposure were studied by gastric intubation of alcohol to chow-fed females for the duration of pregnancy. The doses used approximated 4 and 5 shots of 80 proof liquor per day by a person weighing 150 lb. These offspring were sacrificed at 2, 6, and 21 days postnatal and cardiac myocytes prepared as above. Heart weights were determined and cardiac myocytes were analyzed for cell length, volume, cross-sectional area, and percent binucleation. Additionally, nuclear DNA content was measured in all of the 21 day offspring. Statistical analysis of the data showed no significant differences between hearts exposed to prenatal alcohol and nonexposed controls with either regimen with the exception of percent binucleation which was significantly but only slightly higher in the 6-day-old hearts. These findings are discussed in relation to anatomical heart defects found in patients with full fetal alcohol syndrome.

Chronic prenatal nicotine exposure sensitizes rat brain to acute postnatal nicotine challenge as assessed with ornithine decarboxylase

Prenatal exposure to nicotine has been shown to produce postnatal up-regulation of central nervous system nicotinic receptors and to alter subsequent differentiation of neural tissues. In the current study, pregnant rats received nicotine infusions of 6 mg/kg/day throughout gestation, administered by osmotic minipump implants; the postnatal development of cholinergic receptor reactivity was examined through measurements of the ability of acute nicotine administration to stimulate midbrain + brainstem ornithine decarboxylase (ODC) activity, a key regulatory enzyme in neural cell differentiation and growth. In control rats, the ODC response to nicotine was absent at birth and developed during the second postnatal week in parallel with the known ontogenetic rise of nicotinic receptors. Offspring of the nicotine-infused dams exhibited hyper-reactivity of ODC to postnatal acute nicotine challenge: the response developed earlier than in controls and subsequently the magnitude of the effect was 2–3 times greater. Since the development of cholinergic transmission influences differentiation of target cells, alterations in cholinergic nicotinic receptor mediated responses likely explain the delayed appearance of abnormal cell differentiation associated with prenatal nicotine.

Does chronic prenatal methadone exposure affect β-receptor subtypes in placental, fetal and maternal brain homogenates?

Computer competition analysis of 3H-DHA ( 3H-dihydroalprenolol, a nonselective β-adrenergic radioligand) binding in the presence of unlabeled metoprolol (a β 1-selective antagonist) indicates the existence of both β 1- and β 2-adrenergic receptor subtypes in and confirms previous reports that both β-adrenoceptors are present in adult rat cortex. In the fetal brain (20th day of gestation), however, only β 1-receptors were detected. Pregnant rats were chronically exposed to methadone from day 7 to day 20 of gestation via implanted osmotic minipumps (6.3–9.0 mg/kg/day). This treatment schedule did not induce a change in the affinity and density of either β-receptor subtype in the placental, fetal and maternal brain homogenates. The results are discussed in terms of the reported monoaminergic and opiate receptor functional interactions.

Structural and functional effects of prenatal cocaine exposure in adult rat brain

The long-term effects of cocaine exposure early in development on the metabolic function of major central neuronal systems in the rat are reported in this study. Pregnant Wistar rats were administered either 60 mg/kg cocaine or the vehicle from gestation day (G) 8 through 22 via daily gastric incubation. Sixty-day-old male offspring were examined using the quantified deoxyglucose autoradiographic method. Of the 45 structures examined, 2 cortical and 14 subcortical structures showed statistically significant alterations in glucose metabolism compared to controls. The primary somatosensory and motor cortices showed significant decreases. The hypothalamus contained the greatest concentration of nuclei showing significant changes in activity. All of these changes were decreases. The nigrostriatal pathway, the medial forebrain bundle, the hippocampus, septum and amygdala were all significantly less metabolically active in the exposed offspring. The subcortical sensory systems did not appear to be affected at the dose of cocaine studied. Adjacent sections incubated in 1nM [ 3H]SCH 23390 showed an increase in the concentration of D 1 receptors in the substantia nigra, pars reticulata. Forebrain dopaminergic regions which showed decreased glucose metabolism did not appear to have altered SCH 23390 binding. Although size determinations were made on several cortical and subcortical structures, none were significantly affected by prenatal cocaine. Effects of chronic prenatal cocaine exposure on adult brain metabolism in several neuronal systems were identified at doses which had no significant effects on adult brain or body size. These data support the hypothesis that cocaine use during pregnancy produces permanent neurological effects at doses below those which produce growth retardation and terata.

Effects of prenatal exposure to chronic caffeine on locomotor and emotional behavior

Following chronic prenatal exposure to 24 or 44 mg/kg per day caffeine added throughout gestation to the drinking water of pregnant rats, open-field behavior and latencies to emerge from a dark to a brightly lit area were observed in offspring at mean ages of 73, 117, and 171 days. The higher dose decreased locomotor activity at all ages and increased defecation for females and the number of male rats that failed to emerge in the emergence tests. Prenatal caffeine also increased relative adrenal weights in 90-day-old male subjects. It was concluded that prenatal exposure to 44 mg/kg per day caffeine led to increased emotional reactivity in the offspring and thus decreased locomotor activity.

The effects of chronic prenatal exposure to dietary msg on later development, behavior and brain histology of rat offspring

International Journal of Developmental NeuroscienceVolume 3, Issue 4 p. 459-459 Neurotrophic Factor and Metabolic Aspect The effects of chronic prenatal exposure to dietary msg on later development, behavior and brain histology of rat offspring V.E. Grimm, V.E. GrimmSearch for more papers by this authorB. Frieder, B. FriederSearch for more papers by this author V.E. Grimm, V.E. GrimmSearch for more papers by this authorB. Frieder, B. FriederSearch for more papers by this author First published: 1985 https://doi.org/10.1016/0736-5748(85)90189-3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume3, Issue41985Pages 459-459 RelatedInformation

Altered respiratory control in newborn puppies after chronic prenatal exposure to α- l-acetylmethadol (LAAM)

Respiratory studies were conducted on newborn puppies chronically exposed to α- l-acetylmethadol ·HCl (LAAM) during portions of gestation. Bitches received daily oral doses of LAAM from the second week through the sixth week of pregnancy (LAAM-6) or through the end of a 9-week prenancy (LAAM-9), but not after parturition. LAAM-9 pups displayed narcotic abstinence signs during the first week after birth, while LAAM-6 pups did not. LAAM-9 pups had increased tidal volume, respiratory frequency, alveolar ventilation and O 2-consumption and decreased alveolar CO 2-tension during the first week of life compared to placebo-treated controls. The LAAM-9 CO 2-response curve was significantly displaced to the left of control. These data are consistent with relative hyperventilation during neonatal withdrawal from LAAM. LAAM-6 pups had decreased tidal volume and alveolar ventilation during 4 of the 6 weeks studied. These changes in ventilation were associated with a decrase in O 2 consumption. By 6 weeks after birth CO 2-responses curves of both LAAM-9 and LAAM-6 pups were shifted to the right of control. These changes in CO 2-responsiveness suggest the possibility of prolonged disturbances of respiratory control which may continue beyond the sixth week of life.

A Halothane‐Related Effect on Rat Brain Myelination: A Comparison of Chronic Prenatal or Postnatal Exposure

Rats were exposed to 0.5% halothane in air for 8 h per day during the intervals (1) 5 days postconception to birth, (2) birth to 5 days postnatal age, or (3) birth to 10 days postnatal age. Controls were exposed to an equivalent flow of air. Prenatal exposure had no significant effect on body or brain weight and no subsequent effect on the relative synthesis of brain subcellular membranes. Five days of postnatal exposure caused a 10% reduction in body and brain weight and a 10% relative reduction in the synthesis of brain myelin. The effect persisted throughout the period rapid postnatal brain myelination. Ten days of postnatal exposure produced equivalent, more severe effects on body and brain weights and a more severe effect on myelin synthesis. Postnatal exposure had no apparent effect on the relative synthesis of non-myelin particulate proteins.

Ventilatory response to carbon dioxide of infants following chronic prenatal methadone exposure

Nine infants chronically exposed to methadone in utero were studied from birth to 7 weeks of age (66 studies). The maternal dose of methadone/HCl during the third trimester ranged from 14 to 70 mg orally once a day. The mean (range) of serum methadone t 1/2 in the neonates was 53 hours (22 to 113). In the first four days of life the methadone-exposed infants had a significantly (P less than 0.005) decreased sensitivity to carbon dioxide compared to control infants as measured by the slope of the ventilatory response curve. The mean slope +/- SD for the methadone-exposed infants, 10.4 +/- 7.7 ml/minute/kg mm Hg, was one third that of the control group (30.0 +/- 9.9 ml/minute/kg/mm Hg). Total ventilation, respiratory frequency, oxygen consumption, and end-tidal PCO2 were not significantly different in the two groups. The depressed ventilatory response to carbon dioxide persisted for an average of 15 days and lasted as long as 31 days in one infant. The time required to achieve a normal slope was not related to the size of the maternal methadone dose, to neonatal serum methadone t 1/2, or to the severity of and therapy for methadone withdrawal. If this abnormality in sensitivity to carbon dioxide persists beyond the neonatal period in some infants, it may contribute to the increased incidence of the sudden infant death syndrome among infants exposed to methadone in utero. Measurement of the ventilatory response to carbon dioxide may be clinically useful to determine which of these infants are at risk for SIDS.