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Results for “Fetal Alcohol Spectrum Disorders”

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At least 199 records · Page 11Linked to original sources
PubMed1993

Ethanol alters hormone production in cultured human placental trophoblasts.

Maternal alcohol abuse during pregnancy can lead to abnormalities in fetal development, including the fetal alcohol syndrome (FAS). Although intrauterine growth retardation is a hallmark of FAS, the pathophysiology is not fully understood. A contributing factor may be altered placental function, which could affect fetal growth and development. As a major endocrine organ during pregnancy, changes in the production of placental hormones could affect pregnancy and possibly fetal development. In this study, the effect of continued exposure to ethanol on placental hormone production was examined using cultured human placental trophoblasts. Ethanol exposure involved diffusion of ethanol from the atmosphere into the culture medium. This was refreshed daily, leading to daily peak concentrations of 280 to 300 mg/dl (60-65 mM) at 16 to 24 hr. This ethanol exposure for 2 or 4 days significantly increased the production of human chorionic gonadotropin and progesterone by the cultured trophoblasts. However, ethanol treatment had no effect on human placental lactogen production. Acute stimulation (10 min) of cultured trophoblasts with adenosine (50 microM) normally results in increased production of cyclic adenosine 3',5'-monophosphate (cAMP). With ethanol exposure, adenosine-stimulated cAMP production was significantly elevated relative to that in controls. However, the effect of ethanol on adenosine-stimulated cAMP did not appear to be secondary to chronic alterations in adenosine in the culture medium. Measurement of adenosine in the culture medium revealed no difference in concentration or production between control and ethanol treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1993

Effect of ethanol exposure on circulating levels of insulin-like growth factor I and II, and insulin-like growth factor binding proteins in fetal rats.

Maternal ethanol (ETOH) exposure is associated with impaired fetal growth. Because insulin-like growth factors (IGFs) are thought to be important in the regulation of fetal somatic growth, we examined the influence of maternal ETOH exposure on fetal growth and plasma levels of IGF-I, IGF-II, and IGF binding proteins (IGFBPs) in the rat model. Control (A) dams were fed a standard rat chow ad libitum. ETOH (E) consuming dams were fed a 36% ETOH diet, and pair-fed (P) dams were fed isocaloric amounts of a control liquid diet. All animals were killed on day 20 of gestation. Plasma concentrations of IGF-I and -II were determined by radioimmunoassay after formic acid-acetone extraction and heat inactivation of IGFBPs. Levels of IGFBPs in fetal plasma were estimated by Western ligand blotting after protein separation by SDS-PAGE and electrotransfer to nitrocellulose. Membranes were probed with [125I]IGF-I, and IGFBPs were identified by autoradiography, quantified by scanning densitometry and results expressed relative to corresponding IGFBPs in control fetal plasma. Maternal weight gain from conception to 20 days of pregnancy was reduced for E compared to P and A dams (p < 0.05 E vs. P or A). The same pattern was reflected in fetal weight that tended to be lower in P compared with A pups, and was significantly reduced in E pups compared with both groups (p < 0.0001 E vs. P or A). Thus, fetal growth was more retarded in E animals despite equal caloric and protein intake by E and P dams.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effects of prenatal exposure to alcohol, smoking, and illicit drugs on postpartum somatic growth.

The association of fetal growth retardation with prenatal exposure to alcohol, smoking, opiates, and cocaine is well documented, but relatively little is known about the effects of these exposures on postpartum growth. This study assessed physical growth from birth through 6.5 and 13 months in 412 black, inner-city infants recruited on the basis of their mothers' use of alcohol and/or cocaine during pregnancy. Prenatal alcohol exposure was associated with a slower rate of growth during the first 6.5 postpartum months. This postnatal growth retardation was associated with maternal drinking during a critical period--the latter part of gestation--and was not related to drinking at the time of conception or to postnatal exposure to alcohol from breast-feeding. By contrast, smoking and cocaine use during pregnancy were associated with faster postnatal weight gain. Although maternal smoking was correlated with shorter stature at 6.5 and 13 months, this effect was attributable to maternal drinking during pregnancy, suggesting that the association of maternal smoking with shorter childhood stature reported elsewhere may be due to prenatal alcohol exposure, which was not controlled in prior studies.

Adolescent↗
PubMed1995

Independent associations among maternal alcohol consumption and infant thyroxine levels and pregnancy outcome.

Studies with animal models of alcohol-related birth defects (ARBDs) suggest that reductions in circulating thyroid hormones, including thyroxine (T4), may be a persistent postnatal effect of fetal alcohol exposure. The few clinical reports of children with fetal alcohol syndrome (FAS) that address thyroid system function generally reported that FAS children have thyroid hormone levels within normal limits. For the current study, data bases from the Fetal Alcohol Research Center and the Michigan Department of Public Health Newborn Screening Program were assessed to correlate measures of maternal drug use during pregnancy and infant outcome (gestational age at birth, birthweight, "fetal growth"), with infant whole-blood T4 levels. Multiple regression analyses accounted for demographic factors, infant age at testing, and variation in the T4 assay. As expected, alcohol intake and smoking each had a substantial negative impact on birthweight, gestational age at birth, and fetal growth, assessed as birthweight corrected for gestational age. Infant T4 levels were positively related to birthweight and gestational age and were more strongly related to fetal growth. Infant T4 levels were not influenced significantly by either maternal smoking or alcohol consumption. Smoking- and alcohol-related reductions in birthweight, gestational age, or fetal growth were not associated significantly with variations in infant T4. Interesting questions remain regarding species differences and the influences of maternal alcohol consumption on T4 metabolism as a mechanism for ARBDs. However, the current data do not support the hypothesis that maternal alcohol consumption, or smoking, during pregnancy leads to compromised thyroid system function in newborn humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Ethanol elevates fetal serum glutamate levels in the rat.

Glutamate is an important excitatory neurotransmitter. However, a sustained elevation of glutamate in the extracellular space may be toxic to neurons. Because the blood-brain barrier is incomplete in the developing fetus, an elevation of fetal serum glutamate could expose the immature, growing brain to potentially toxic levels of extracellular glutamate. Chronic ethanol consumption during pregnancy is associated with an increased risk for a complex array of congenital anomalies, including alterations in the CNS, a hallmark of the fetal alcohol syndrome. Some central nervous system changes appear to involve the glutamate receptor, including reduced number and altered function. One mechanism for receptor downregulation may be a sustained elevation in extracellular glutamate. We hypothesize that chronic ethanol exposure during pregnancy leads to an elevation in fetal serum glutamate. When rats were fed ethanol-containing liquid diet throughout pregnancy, growth retardation of fetuses was observed at sacrifice (gestation day 20). Within each group, ethanol-fed, pair-fed, and ad libitum chow-fed, serum glutamate levels were generally higher in the fetus than in the dam. Ethanol treatment had no effect on fetal or maternal serum glutamine, a reciprocal metabolite of glutamate. In contrast, ethanol treatment increased serum glutamate levels in the fetal serum by nearly 50%, compared with either of the control groups. Maternal serum glutamate was not affected. The finding of ethanol-induced elevation of fetal serum glutamate suggests that the developing brain might be concurrently exposed to elevated levels of extracellular glutamate. Chronic exposure to elevated glutamate during critical periods of brain development may contribute to the pathogenesis of the fetal alcohol syndrome.

Animals↗
PubMed1995

Perinatal maternal ethanol effects on pregnant mice and on offspring viability and growth: influences of exposure time and weaning diet.

C57BL/6 mice were maintained on liquid diets containing 27.5% ethanol-derived calories beginning on gestational day 12. For one group, the liquid diet was replaced with laboratory chow on the morning of gestational day 18, approximately 24 hr before delivery. For a second group, the diet was continued for 7 days postnatally. Two additional groups were pair-fed isocaloric sucrose diets, and a final group was maintained on normal laboratory chow. The mice consumed sufficient amounts of diet to provide near 30 g ethanol/kg/day during pregnancy and slightly greater amounts during the first postpartum week. The ethanol diet produced no maternal deaths and did not alter weight gain during gestational days 12-17 of pregnancy. The results confirmed previous reports that dietary ethanol exposure under conditions that have rather minor effects on the pregnant mouse can substantially affect the fetus. As previously reported, when exposure was terminated 24 hr before delivery, neonatal mortality was elevated by approximately 30%, but birth weight was not altered. When the diet was extended into the lactation period, mortality was delayed but not reduced, possibly by reducing the severity of ethanol withdrawal. Birthweight was reduced by 10% when exposure continued until birth, suggesting that low birthweights for fetal ethanol-exposed (FEE) mice can be eliminated by terminating exposure approximately 24 hr before delivery. As in previous reports, FEE mice with normal birthweights had an attenuated preadolescent growth spurt, suggesting that low birthweights and attenuated postnatal growth are likely mediated by different mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

Use of record linkage to examine alcohol use in pregnancy.

BACKGROUND: To date, no population-level data have been published examining the obstetric and neonatal outcomes for women with an alcohol-related hospital admission during pregnancy compared with the general obstetric population. This information is critical to planning and implementing appropriate services. METHODS: Antenatal and delivery admissions to New South Wales (NSW) hospitals from the NSW Inpatient Statistics Collection were linked to birth information from the NSW Midwives Data Collection over a 5-year period (1998-2002). Birth admissions were flagged as positive for maternal alcohol use where a birth admission or any pregnancy admission for that birth involved an alcohol-related International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Australian Modification (ICD-10-AM) code. Key demographic, obstetric, and neonatal variables were compared for births to mothers in the alcohol group with births where no alcohol-related ICD10-AM was recorded. RESULTS: A total of 416,834 birth records were analyzed over a 5-year period (1998-2002). In this time, 342 of these were coded as positive for at least 1 alcohol-related ICD-10-AM diagnosis. Mothers in the alcohol group had a higher number of previous pregnancies, smoked more heavily, were not privately insured, and were more often indigenous. They also presented later on in their pregnancy to antenatal services and were more likely to arrive at hospital unbooked for delivery. Deliveries involved less epidural and local and more general anesthesia. Cesarean sections were more common to women in the alcohol group and were performed more often for intrauterine growth retardation. Neonates born to women in the alcohol group were smaller for gestational age, had lower Apgar scores at 5 minutes, and were admitted to special care nursery more often. CONCLUSIONS: This study shows that linked population-level administrative data provide a powerful new source of information for examining the maternal and neonatal outcomes associated with alcohol use in pregnancy.

Adult↗
PubMed1979

Effects on the child of alcohol abuse during pregnancy. Retrospective and prospective studies.

Retrospective and prospective investigations of children to alcoholic women gave an incidence of fetal alcohol lesion of one per 300 deliveries of whom half had the complete fetal alcohol syndrome. Perinatal and infant mortalities were increased seven to tenfold and low birth weight (less than or equal to 2 500 g), preterm deliveries (less than 37 weeks) and smallness for gestational age (less than -2 S.D.) were increased eightfold, threefold and twelvefold, respectively. Small size at birth correlated with reduced mental performance later in life, 58% had IQ below 85 and 19% below 70.8% had cerebral palsy. The incidence of cerebral palsy associated with maternal inebriety was 1/5 000 deliveries, i.e. every sixth case of cerebral palsy. Tracing of alcoholic women during pregnancy and treatment gave favourable effect on intrauterine growth when sobriety could be induced early in pregnancy but could not protect from functional brain disturbance measured by neurological performance and be evoked response electroencephalography. Damage to the fetus by alcohol is now the largest known health hazard by a noxious agent that is preventable.

Alcoholism↗
PubMed1995

A population-based study on the causes of mild and severe mental retardation.

The causes of mental retardation (MR) were studied as part of a multidisciplinary epidemiological case-control study in 151 mentally retarded patients identified by screening four age cohorts (12,882 children) at 8-9 years of age in the province of Kuopio, Finland. The causes of MR in 77 severely retarded (SD < or = -3 SD) and 74 mildly retarded (-2 > SD > -3) children were divided into pre-, peri-, postnatal and unknown groups according to the probable time of onset. The causes were pre-, peri-, postnatal and unknown in 60%, 9%, 8% and 23%, and 22%, 1%, 3% and 74%, in the two populations, respectively. Genetic causes were found in 28% of all 151 cases; the three most common subgroups were trisomy 21, fragile X syndrome and aspartylglycosaminuria (13%, 4% and 2% respectively). The study design used provided reliable information on the causes of MR and also demonstrated those forms of genetic metabolic diseases typical of Finnish inheritance.

Acetylglucosamine↗
PubMed2004

Methylphenidate restores ventral tegmental area dopamine neuron activity in prenatal ethanol-exposed rats by augmenting dopamine neurotransmission.

Altered neurotransmission in the mesolimbic dopamine (DA) system has been suggested to be the underlying cause of attention problems commonly observed in children with fetal alcohol spectrum disorder (FASD). Methylphenidate is effective in treating attention problems in children with FASD. However, the underlying mechanism is currently unknown. We have shown previously that reduced ventral tegmental area (VTA) DA neuron activity in prenatal ethanol-exposed animals can be normalized by DA agonist treatment. In the present study, we investigated the possibility that similar mechanism mediates the effect of methylphenidate using the in vivo extracellular single-unit recording technique in anesthetized animals. We observed that reduced VTA DA neuron activity in prenatal ethanol-exposed animals was normalized by methylphenidate. The effect of methylphenidate was mediated by increased extracellular levels of DA instead of norepinephrine because this effect was not altered by the coadministration of prazosin, an alpha(1) receptor antagonist, and was mimicked by the application of DA transporter blockers, nomifensine and 1-2(-[bis(4-flurophenyl)methoxy]ethyl)-4-(3-phenyl)piperazine dihydrochloride (GBR 12909). These observations support our hypothesis that depolarization inactivation is the cause of prenatal ethanol exposure-induced reduction in VTA DA neuron activity. We speculate that methylphenidate normalized the activity of VTA DA neurons by increasing extracellular DA levels in the VTA and the activation of somatodendritic DA autoreceptors. As a result, the depolarization inactivation was removed by hyperpolarization. The normalized VTA DA neuron activity in prenatal ethanol-exposed animals may contribute to a restoration of DA neurotransmission and the therapeutic effect of methylphenidate in attention problems in children with FASD.

Amphetamine↗
PubMed2006

Effects of prenatal ethanol exposure on the excitability of ventral tegmental area dopamine neurons in vitro.

Prenatal ethanol exposure leads to a persistent reduction in the number of spontaneously active dopaminergic (DA) neurons (DA neuron population activity) in the ventral tegmental area (VTA) in developing and adult animals. This effect might contribute to the dysfunction of the mesolimbic/cortical DA system and attention problems in children with fetal alcohol spectrum disorders. To characterize the underlying cellular mechanism for prenatal ethanol exposure-induced reduction in VTA DA neuron population activity, we used the whole-cell patch-clamp technique to study the membrane properties of putative VTA DA neurons in brain slices in 2- to 3-week-old control and prenatal ethanol-exposed animals. The results show that prenatal ethanol exposure did not impair the spontaneous pacemaker activity in putative VTA DA neurons but reduced the frequency of evoked action potentials. In addition, prenatal ethanol exposure led to a reduction in hyperpolarization-induced cation current (I(h)) and an up-regulation of somatodendritic DA autoreceptors. The above prenatal ethanol exposure-induced changes could decrease the excitability of VTA DA neurons. However, they do not seem to play a role in reduced VTA DA neuron population activity in vivo, an effect thought to be mediated by excessive excitation leading to depolarization inactivation. Taken together, the above results indicate that prenatal ethanol exposure-induced reduction in VTA DA neuron population activity in vivo is not caused by changes in the intrinsic pacemaker activity or other membrane properties and could instead be caused by altered inputs to VTA DA neurons.

Action Potentials↗
PubMed1982

Maternal ethanol exposure induces transient impairment of umbilical circulation and fetal hypoxia in monkeys.

When ethanol was administered intravenously to pregnant monkeys, a transient but marked collapse of umbilical vasculature was observed uniformly within about 15 minutes. The ethanol-induced impairment of umbilical circulation produced severe hypoxia and acidosis in the fetus; recovery occurred during the succeeding hour. This striking interruption of feto-placental circulation may explain one of the mechanisms of mental retardation, a frequent manifestation in children afflicted with fetal alcohol syndrome.

Acetaldehyde↗
PubMed2003

Whole body insulin resistance in rat offspring of mothers consuming alcohol during pregnancy or lactation: comparing prenatal and postnatal exposure.

This study examined the effects of maternal ethanol (EtOH) consumption during pregnancy or lactation on glucose homeostasis in the adult rat offspring. Glucose disposal was determined by minimal model during an intravenous glucose tolerance test in rats that had a small or normal birth weight after EtOH exposure in utero and in rats whose mothers were given EtOH during lactation only. All three EtOH groups had decreased glucose tolerance index and insulin sensitivity index, but their glucose effectiveness was not different from that of controls. In addition, EtOH rat offspring that were small at birth had elevated plasma, liver, and muscle triglyceride levels. The data show that EtOH exposure during pregnancy programs the body to insulin resistance later in life, regardless of birth weight, but that this effect also results in dyslipidemia in growth-restricted rats. In addition, insulin resistance is also evident after EtOH exposure during lactation.

Animals↗
PubMed1985

Effect of intrauterine ethanol exposure on fetal lung growth.

Lung weight, DNA, RNA, protein, and total body weight were analyzed in fetuses from 14 pregnant Sprague-Dawley rats fed a nutritionally complete liquid diet containing v/v 6% ethanol (ethanol group). Each ethanol rat was matched with an isocalorically pair-fed animal (control group) who received the same liquid diet with carbohydrate substituted for ethanol. The rats were killed on day 20 of gestation. The mean maternal blood ethanol concentration at 0700 h on day 20 was 170 +/- 22 (SE) mg/dl. Compared to controls, ethanol fetuses had reduced body weight (21%), lung dry weight (39%), lung wet weight/body weight ratio (10%), DNA (21%), RNA (25%), protein (28%), and protein/DNA ratio (8%) (p less than 0.05). The results indicate that prenatal ethanol exposure inhibits cellular growth in the fetal lung, resulting in hypoplastic lungs which have fewer and smaller cells. The effect on the lung appears to be greater than on the body as a whole. These hypoplastic lungs may be predisposed to the development of pulmonary disease and may explain observations of more frequent and severe lower respiratory infections in children with prenatal ethanol exposure.

Animals↗
PubMed1985

Zinc deficiency acts as a co-teratogen with alcohol in fetal alcohol syndrome.

Because alcoholism has adverse effects on zinc nutrition and many pregnant women consume less than the recommended dietary allowances of zinc, we postulated that zinc deficiency acts as a co-teratogen with alcohol in the fetal alcohol syndrome. We compared the effects of alcohol on progeny of pregnant mice fed a zinc-deficient diet compared to those fed a diet with adequate zinc. Pregnant CBA mice (n = 66) were fed the Lieber-DeCarli liquid diet with 0, 15, or 20% ethanol-derived calories containing 0.3 (low) or 8.5 (high) micrograms zinc/ml. Dams were sacrificed on day 18 of gestation. Resorptions, malformations, and individual fetal weights were recorded. Analysis of fetuses included assays for zinc, assessment of soft tissue malformations, and alizarin red staining for skeletal malformations. Fetal weights were lower in the groups fed the zinc-deficient diet for each concentration of alcohol (p less than 0.005). The groups fed the combination of low zinc plus alcohol had 37-52% resorptions, while the animals on the zinc-deficient diet without alcohol or the high zinc diet with alcohol had 0-2% resorptions. Skeletal malformations were related to alcohol concentration but not zinc intake, while external malformations were higher in those maintained on the low zinc-ethanol diet. These results suggest that zinc deficiency potentiated the teratogenic effects of alcohol and that nutritional intervention for alcoholic women during pregnancy might reduce the incidence or severity of fetal alcohol syndrome.

Abnormalities, Multiple↗