Effects of Prenatal Exposure to Alcohol Plus Caffeine in Rats: Pregnancy Outcome and Early Offspring Development

The factors determining susceptibility to fetal alcohol syndrome (FAS) are not fully understood. We used an animal model of alcohol-related birth defects to assess the coteratogenic potential of caffeine as a risk factor in FAS. Rats were exposed prenatally to alcohol (˜15 g/kg/day) with or without caffeine (˜84 mg/kg/day) from gestation days 6 through 20 via liquid diet. All control groups were pair-fed to the alcohol-exposed groups. In addition, some controls had free access to lab chow and water. Prenatal exposure to alcohol or caffeine reduced both maternal weight gain during pregnancy and birth-weight of offspring. The combination of alcohol plus caffeine produced an additive effect in reducing birthweight and synergistic effects in increasing postnatal offspring mortality. Prenatal alcohol exposure had a significant negative impact on several developmental indices, including grip strength and negative geotaxis. Prenatal caffeine exposure did not affect maturational measures and did reduce offspring serum levels of the zinc-dependent enzyme alkaline phosphatase. This study in rats demonstrated that caffeine can exacerbate some of the effects of alcohol on prenatal development, specifically reduced birthweight, litter size, and postnatal survival, but that caffeine does not appear to alter prenatal alcohol-induced delays in early postnatal maturation of survivors. The relative impact of intralitter birthweight rank on developmental outcome was also assessed. Birthweight influenced development, but did not interact significantly with either prenatal alcohol or caffeine. The results imply that high levels of maternal caffeine intake in humans could increase the likelihood that a child exposed prenatally to alcohol would be born with significantly lowered birthweight, one of the cardinal diagnostic criteria for FAS.     

Increased Vulnerability to Alcohol-Related Birth Defects in the Offspring of Mothers Over 30

The risk of fetal alcohol syndrome (FAS) is known to increase with Increased maternal age and parity. This study investigated the hypothesis that the deficits in growth and intellectual function seen in non-FAS infants exposed to alcohol at moderate-to-heavy levels are also found disproportionately in the offspring of older mothers. Mothers of 480 African-American, inner-city infants were interviewed at each prenatal clinic visit regarding their use of alcohol during pregnancy. Infants were assessed for physical growth and cognitive development repeatedly through age 13 months. In analyses run separately for the infants of younger and older mothers, alcohol-related deficits were seen most strongly in the offspring of women over 30 years of age. This pattern was not caused by lower levels of drinking by the younger mothers. Age-related increases in maternal body fat-to-water ratio and a faster rate of alcohol metabolism in chronic drinking women may account for the greater vulnerability of the offspring of the older mothers. These data suggest that physiological changes associated with aging and/or chronic drinking may play an important role in the alcohol-related birth defects seen in infants exposed at moderate-to-heavy levels.     

Sibling birthweight as a predictor of macrosomia in women with type 1 diabetes

Aims/hypothesis The aim of this study was to establish the value of maternal HbA₁c levels and older sibling birthweight as predictors of birthweight and macrosomia in the offspring of women with type 1 diabetes.Subjects and methods A total of 214 pregnancies of 107 women with type 1 diabetes were studied. Regression analysis was performed to test the predictive value of the birthweight of the first-born infant, HbA₁c levels, maternal BMI, maternal age and time between subsequent births on the birthweight of the second-born infant. Birthweights were corrected for sex and gestational age. The percentages of first- and second-born infants with macrosomia (weight >90th centile) were calculated and compared.Results Only the birthweight of earlier born infants was significantly related to that of second-born infants (p<0.001) and 40–50% of the variation in the birthweight of second-born infants could be explained by the birthweight of the first-born infants. About 85% of the mothers who gave birth to a macrosomic infant had a macrosomic infant in a subsequent pregnancy.Conclusions/interpretation Although it is clear that glycaemic control contributes to birthweight in women with type 1 diabetes, the birthweight of an earlier born infant appears to be a much better predictor of the birthweight of a subsequent infant than HbA₁c levels during pregnancy. It may, therefore, be used to identify patients at risk of giving birth to a macrosomic infant. Daily home monitoring of glucose levels, rather than HbA₁c levels, should be used for assessment of maternal glycaemia during pregnancy.     

Thiocyanate and Drinking during Pregnancy

Alcohol appears to have a relatively direct effect in decreasing fetal growth; however, it also appears that other factors associated with alcohol consumption may also contribute to lowered birthweight. Three studies have suggested that beverage source of alcohol may be a determinant of decreased intrauterine growth and that beer may have a comparatively greater effect than wine and liquor. Since beer is reported to contain thiocyanate (SCN), a substance which has been implicated as a determinant of fetal growth retardation in relation to cigarette smoking, we studied maternal and fetal serum SCN levels in 82 pregnancies. After controlling for maternal characteristics, gestational age, and tobacco and marijuana use, the quantity of beer consumed was found to have a significant positive correlation with fetal serum SCN (p < 0.005). Consumption of other types of alcoholic beverages was not significantly associated with elevated fetal serum SCN, although the numbers of wine and liquor drinkers in this study were limited. Further research is warranted to explore the possibility that the correlation of beer consumption with increased SCN might provide at least one explanation for the reported linkage of diminished fetal growth and beer drinking .     

Impact of alcohol exposure after pregnancy recognition on ultrasonographic fetal growth measures

BACKGROUND: More than 3 decades after Jones and Smith (1973) reported on the devastation caused by alcohol exposure on fetal development, the rates of heavy drinking during pregnancy remain relatively unchanged. Early identification of fetal alcohol exposure and maternal abstinence led to better infant outcomes. This study examined the utility of biometry for detecting alcohol-related fetal growth impairment. METHODS: We obtained fetal ultrasound measures from routine ultrasound examinations for 167 pregnant hazardous drinkers who were enrolled in a brief alcohol intervention study. The fetal measures for women who quit after learning of their pregnancies were compared with measures for women who continued some drinking throughout the course of their pregnancies. Because intensity of alcohol consumption is associated with poorer fetal outcomes, separate analyses were conducted for the heavy (average of >or=5 drinks per drinking day) alcohol consumers. Fetal measures from the heavy-exposed fetuses were also compared with measures from a nondrinking group that was representative of normal, uncomplicated pregnancies from our clinics. Analyses of covariance were used to determine whether there were differences between groups after controlling for influences of gestational age and drug abuse. RESULTS: Nearly half of the pregnant drinkers abstained after learning of their pregnancies. When women reportedly quit drinking early in their pregnancies, fetal growth measures were not significantly different from a non-alcohol-exposed group, regardless of prior drinking patterns. Any alcohol consumption postpregnancy recognition among the heavy drinkers resulted in reduced cerebellar growth as well as decreased cranial to body growth in comparison with women who either quit drinking or who were nondrinkers. Amphetamine abuse was predictive of larger cranial to body growth ratios. CONCLUSIONS: Alterations in fetal biometric measurements were observed among the heavy drinkers only when they continued drinking after becoming aware of their pregnancies. Although the reliance on self-reported drinking is a limitation in this study, these findings support the benefits of early abstinence and the potential for ultrasound examinations in the detection of fetal alcohol effects.     

Fetal and maternal thyroid hormone responses to ethanol exposure during the third trimester equivalent of gestation in sheep

BACKGROUND: Abnormal thyroid hormone system function in the mother or fetus during pregnancy can result in brain defects, some of which resemble those found in children with fetal alcohol syndrome. It has been hypothesized that ethanol may act to mediate alcohol-related birth defects in part by altering thyroid hormone system function. We investigated whether a binge pattern of maternal ethanol consumption over the last trimester equivalent of gestation in sheep results in an alteration in fetal or maternal thyroid function. METHODS: Pregnant ewes received saline or ethanol beginning on day 109 of gestation (term, 145 days) for three consecutive days per week followed by 4 days without exposure. The fetuses were surgically instrumented on day 113, and experiments were performed on days 118 or 132. Fetal and maternal blood samples were collected, and plasma tri-iodothyronine (T3), thyroxine (T4), and free T4 concentrations were measured. RESULTS: Fetal T3 and T4 on day 118, fetal T3 on day 132, and maternal T3 on day 132 were lower in response to ethanol. Fetal and maternal free T4 and maternal T4 did not change in response to ethanol. Fetal thymus and adrenal weights were reduced in response to ethanol. CONCLUSIONS: We conclude that, in sheep, maternal ethanol exposure during the third trimester equivalent resulting in blood ethanol concentrations that are commonly achieved by ethanol abusers decreases circulating thyroid hormone concentrations in the mother and fetus and fetal thyroid and thymus mass.     

Maternal risk factors for fetal alcohol syndrome and partial fetal alcohol syndrome in South Africa: a third study

Objectives: This is a third exploration of risk factors for the two most severe forms of fetal alcohol spectrum disorders (FASD), fetal alcohol syndrome (FAS) and Partial FAS (PFAS), in a South African community with the highest reported prevalence of FAS in the world. Methods: In a case control design, interview and collateral data concerning mothers of 72 first grade children with FAS or PFAS are compared with 134 randomly selected maternal controls of children from the same schools. Results: Significant differences were found between the mothers of FASD children and controls in socio‐economic status, educational attainment, and a higher prevalence of FASD among rural residents. The birth order of the index children, gravidity, and still birth were significantly higher among mothers of FASD children. Mothers of children with a FASD are less likely to be married and more likely to have a male partner who drank during the index pregnancy. Current and gestational alcohol use by mothers of FASD children is bingeing on weekends, with no reduction in drinking reported in any trimester in 75 to 90% of the pregnancies that resulted in an FAS child or during 50 to 87% of PFAS‐producing pregnancies. There was significantly less drinking among the controls in the second and third trimesters (11 to 14%). Estimated peak blood alcohol concentrations (BAC)s of the mothers of PFAS children range from 0.155 in the first trimester to 0.102 in the third, and for mothers of FAS children the range is from 0.197 to 0.200 to 0.191 in the first, second, and third. Smoking percentage during pregnancy was significantly higher for mothers of FASD children (82 to 84%) than controls (35%); but average quantity smoked is low in the 3 groups at 30 to 41 cigarettes per week. A relatively young average age of the mother at the time of FAS and PFAS births (28.8 and 24.8 years respectively) is not explained by early onset of regular drinking (mean = 20.3 to 20.5 years of age). But the mean years of alcohol consumption is different between groups, 16.3, 10.7, and 12.1 years respectively for mothers of FAS, FASD, and drinking controls. Mothers of FAS and PFAS children were significantly smaller in height and weight than controls at time of interview. The child’s total dysmorphology score correlates significantly with mother’s weight (?0.46) and BMI (?0.39). Bivariate correlations are significant between the child’s dysmorphology and known independent demographic and behavioral maternal risk factors for FASD: higher gravidity and parity; lower education and income; rural residence; drinks consumed daily, weekly, and bingeing during pregnancy; drinking in all trimesters; partner's alcohol consumption during pregnancy; and use of tobacco during pregnancy. Similar significant correlations were also found for most of the above independent maternal risk variables and the child’s verbal IQ, non‐verbal IQ and behavioral problems. Conclusions: Maternal data in this population are generally consistent with a spectrum of effects exhibited in the children. Variation within the spectrum links greater alcohol doses with a greater severity of effects among children of older and smaller mothers of lower socio economic status in their later pregnancies. Prevention is needed to address known maternal risk factors for FASD in this population.     

Effect of Alcohol on Platelet-Activating Factor Acetylhydrolase Activity in Pregnant and Nonpregnant Mice

Platelet-activating factor (PAF) induces platelet aggregation and hypotension. It has been implicated in embryonic implantation, fetal lung maturation, and parturition. Alcohol abuse is associated with platelet dysfunction, chronic hypertension, and alcohol-related birth defects. We hypothesized that alcohol may cause, in part, these effects by increasing the activity of PAF-acetylhydrolase (PAF-AH), thereby decreasing PAF concentration. Pregnant mice were given 3.5 g/kg of alcohol orally twice daily from gestation days 7–17. PAF-AH was measured on gestation days 5, 14, and 19 in pregnant females. Nonpregnant females were treated and sampled at parallel time intervals. Pair-fed and untreated control groups were also used. The maternal plasma PAF-AH decreased with gestational age in the untreated controls. Alcohol significantly increased PAF-AH levels in both the pregnant and nonpregnant animals. PAF deficiency might contribute to the tocolytic action of alcohol, as well as some alcohol-related pregnancy complications.     

Relation of fetal growth to maternal responses to oral glucose tolerance test throughout gestation

Fetal growth is dependent on transplacental supply of fuels. We aimed to assess the effect of serial changes in maternal glucose tolerance and insulin secretion with advancing pregnancy on maternal-fetal outcomes. Sixty-nine healthy pregnant women were studied over the course of gestation for glucose tolerance, by oral glucose tolerance test (OGTT), and hemoglobin A_1c (HbA_1c), fetal intrauterine growth (by ultrasound) and pregnancy outcome. Seven women had an abnormal OGTT in the third trimester developing gestational diabetes mellitus (GDM), but none of the 12 mothers of large babies (> 3.9 kg) had GDM: the former had the highest post-load glycemic increment, despite an apparently ‘normal’ insulin secretory response, the latter showed the lowest post-load glucose increase in the face of the lowest insulinemic response. Neonatal body weight correlated with maternal gestational weight gain, placental weight, third trimester ratio of incremental plasma insulin and glucose integrated areas under the curve and first and second trimester HbA_1c levels. Fetal growth indices (femur length, biparietal diameter and abdominal circumference) were correlated with both HbA_1c and 2h OGTT. Fetal growth rate is confirmed as being associated with maternal glycemic equilibrium, but one of the main determinants of high infant birthweight seems to be an enhanced maternal insulin sensitivity, accompanied by remarkable gestational weight gain. Received: 11 March 1999 / Accepted in revised form: 1 February 1999     

An Update on Fetal Alcohol Syndrome—Pathogenesis,Risks, and Treatment

Alcohol is a well‐established teratogen that can cause variable physical and behavioral effects on the fetus. The most severe condition in this spectrum of diseases is known as fetal alcohol syndrome (FAS). The differences in maternal and fetal enzymes, in terms of abundance and efficiency, in addition to reduced elimination, allow for alcohol to have a prolonged effect on the fetus. This can act as a teratogen through numerous methods including reactive oxygen species (generated as by products of CYP2E1), decreased endogenous antioxidant levels, mitochondrial damage, lipid peroxidation, disrupted neuronal cell–cell adhesion, placental vasoconstriction, and inhibition of cofactors required for fetal growth and development. More recently, alcohol has also been shown to have epigenetic effects. Increased fetal exposure to alcohol and sustained alcohol intake during any trimester of pregnancy is associated with an increased risk of FAS. Other risk factors include genetic influences, maternal characteristics, for example, lower socioeconomic statuses and smoking, and paternal chronic alcohol use. The treatment options for FAS have recently started to be explored although none are currently approved clinically. These include prenatal antioxidant administration food supplements, folic acid, choline, neuroactive peptides, and neurotrophic growth factors. Tackling the wider impacts of FAS, such as comorbidities, and the family system have been shown to improve the quality of life of FAS patients. This review aimed to focus on the pathogenesis, especially mechanisms of alcohol teratogenicity, and risks of developing FAS. Recent developments in potential management strategies, including prenatal interventions, are discussed.     

Fetal Cerebral Circulation as Target of Maternal Alcohol Consumption

Alcohol (ethanol [EtOH]) is one of the most widely used psychoactive substances worldwide. Alcohol consumption during pregnancy may result in a wide range of morphological and neurodevelopmental abnormalities termed fetal alcohol spectrum disorders (FASD), with the most severe cases diagnosed as fetal alcohol syndrome (FAS). FAS and FASD are not readily curable and currently represent the leading preventable causes of birth defect and neurodevelopmental delay in the United States. The etiology of FAS/FASD remains poorly understood. This review focuses on the effects of prenatal alcohol exposure (PAE) on fetal cerebrovascular function. A brief introduction to the epidemiology of alcohol consumption and the developmental characteristics of fetal cerebral circulation is followed by several sections that discuss current evidence documenting alcohol‐driven alterations of fetal cerebral blood flow, artery function, and microvessel networks. The material offers mechanistic insights at the vascular level itself into the pathophysiology of PAE.     

Epidemiology of FASD in a province in Italy: Prevalence and characteristics of children in a random sample of schools

BACKGROUND: Accurate estimates of the prevalence and characteristics of fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorders (FASD) in a Western European population are lacking and are of particular interest in settings where the usual pattern of alcohol consumption is thought to be daily drinking with meals. To address these issues, an epidemiology study of FAS and other FASD was undertaken in Italian schools. METHODS: Primary schools (n = 25) in 2 health districts of the Lazio region were randomly selected and recruited for the study. Five hundred forty-three children, 50% of those enrolled in first-grade classes, received parental permission to participate in a 2-tiered, active case ascertainment screening process. Detailed evaluation of children selected in a preliminary screening phase was carried out on those who were small for height, weight, and head circumference and/or referred by teachers for suspected learning and behavioral problems. Detailed evaluation was carried out on each child's: (1) physical growth and dysmorphology, (2) psychological development and behavior, and (3) prenatal exposure to alcohol and other risk factors for FASD via maternal interviews. A group of 67 randomly selected children without FASD from the same classes was utilized as a comparison group. RESULTS: Using 2 denominators for prevalence estimation, a conservative one and a strict sample-based estimate, the prevalence of FAS in this province of Italy was 3.7 to 7.4 per 1,000 children. When cases of partial FAS (PFAS) and a case of alcohol-related neurodevelopmental deficits (ARND) were added to FAS cases, the rate of FASD was 20.3 to 40.5 per 1,000 and estimated at 35 per 1,000 overall or between 2.3 and 4.1% of all children. This exceeds previously published estimates of both FAS and FASD for the western world. Detailed data are presented that demonstrate the utility of the guidelines of the revised Institute of Medicine diagnostic criteria for FASD. Children with FASD are significantly more impaired/affected (p < 0.05) than randomly selected comparison children on all measures of growth deficiency, key facial features of FASD, overall dysmorphology scores, language comprehension, nonverbal IQ, and behavior. Maternal reports of current drinking were significantly higher for mothers of FASD children than comparison mothers, but reported rates of overall drinking during pregnancy were not significantly different. In contrast to expectations, daily drinking among mothers of the comparison group was not common. However, dysmorphology scores of the children were significantly correlated with drinking in the second and third trimesters, drinks per current drinking day, and current drinks per month. Finally, children with the physical features of FASD had lower IQs; nonverbal IQ was significantly correlated with head circumference and negatively correlated with overall dysmorphology score, smooth philtrum, and several other facial and physical anomalies characteristic of FAS. CONCLUSIONS: Using careful measures of ascertainment in a primary school setting, these results provide relatively high estimates of the prevalence of FASD and raise the question of whether FASD is more common in the western world than previously estimated.     

Cisapride Use During Human Pregnancy (A Prospective, Controlled Multicenter Study)

The objective of this prospective multicenterstudy was to determine whether cisapride is associatedwith increased risk of malformations, spontaneousabortions, or decreased birthweight when used during pregnancy. Cases were paired for age, smoking,and alcohol consumption with controls exposed tononteratogens, as well as with disease-paired controls.One hundred and twenty-nine pregnant women were exposed to cisapride during pregnancy, including 88during the period of fetal organogenesis. There were nodifferences in maternal history, birthweight,gestational age at delivery, and rates of livebirths,spontaneous or therapeutic abortions, fetal distress, andmajor or minor malformations among groups. It isconcluded that exposure to cisapride during pregnancy isnot associated with a major increased risk ofmalformations or spontaneous abortions or with decreasedbirthweight.     

Maternal, infant, and delivery factors associated with neonatal thyroid hormone status.

BACKGROUND: Thyroid function is dynamic during the perinatal period with many factors potentially influencing maternal, fetal and neonatal TSH and thyroid hormone levels. We sought to identify the impact of numerous maternal, fetal and delivery attributes on thyroid parameters in newborns. METHODS: This was a cross sectional study of 300 newborns. Detailed information was obtained from medical records and multiple characteristics from the record were tested as predictors of cord blood serum total T4, free T4 and TSH and infant T4 levels from the Maryland newborn screening program. MAIN OUTCOME: Outcomes are levels of thyroid stimulating hormone (TSH), thyroxine (T(4)), and free T(4) in newborn cord serum and total T(4) in postnatal heelstick bloodspot samples. RESULTS: Multivariate models identified a number of variables that are independently associated with thyroid hormone levels: higher birth order (lower cord TSH); older maternal age (lower cord total T(4)); pregnancy-induced hypertension and/or preeclampsia (lower cord total T(4) and free T(4)); gestational diabetes (higher cord free T(4)); sexually transmitted disease during pregnancy (lower cord TSH); alcohol use during pregnancy (lower cord TSH); thyroid condition/medications (higher bloodspot total T(4), both neonatal and subsequent); Asian ancestry (higher cord TSH); male sex (higher TSH and lower neonatal bloodspot total T(4)); and C-section (lower cord TSH). Gestational age was independently associated with lower cord TSH, higher cord total T(4), and higher neonatal and subsequent bloodspot total T(4). CONCLUSIONS: Fetal and newborn thyroid hormone levels during the perinatal period are dynamic and influenced by several biological and delivery related factors. Efforts to identify fetal thyroid disruptors in late gestation must carefully consider these factors.     

Markers of oxidative stress and systemic vasoconstriction in pregnant women drinking > or =48 g of alcohol per day

Background: The precise pathway by which alcohol causes the characteristic features of fetal alcohol spectrum disorders is unknown. Proposed mechanisms for fetal injury from maternal alcohol use include cellular damage from oxidative stress and impaired fetal oxygenation related to maternal systemic vasoconstriction. Our objective was to compare the levels of urinary markers of oxidative stress and systemic vasoconstriction between women consuming large amounts of alcohol during pregnancy and women who did not drink alcohol during pregnancy. Methods: Pregnant women consuming ≥48 g alcohol per day (n = 29) on average and pregnant women who abstained from alcohol use (n = 39) were identified using detailed interviews and home visits. Random maternal urine specimens were collected. Urinary levels of the oxidative stress marker, 8‐isoprostane F2α, and of the vasoactive prostaglandin metabolites, 2,3‐dinor‐6‐keto‐prostaglandin F1α (a vasodilator) and 11‐dehydro‐thromboxane B2 (a vasoconstrictor), were measured using mass spectrometric methods. All analyte levels were corrected for urinary creatinine. Results: In crude analyses, there was no significant difference in 8‐isoprostane F2α between pregnant drinkers and nondrinkers (2.16 vs. 2.08 ng/mg creatinine, respectively, p = 0.87). There were no significant differences between the drinking and nondrinking groups in levels of 2,3‐dinor‐6‐keto‐prostaglandin F1α (1.03 vs. 1.17 ng/mg creatinine, repectively, p = 0.50), 11‐dehydro‐thromboxane B2 (0.72 vs. 0.59 ng/mg creatinine, respectively, p = 0.21), or the ratio of vasodilatory metabolite to vasoconstrictive metabolite (1.73 vs. 2.72, respectively, p = 0.14). Adjusting for maternal age, marital status, smoking, and gestational age at sampling did not substantially alter the results. Conclusion: Our results show no difference in levels of urinary eicosanoid markers of oxidative stress and systemic vasoconstriction between pregnant women who drink heavily and pregnant women who abstain. These findings speak against a role for maternal oxidative stress or systemic vasoconstriction in the pathogenesis of alcohol damage to the fetus.     

Safety of first trimester exposure to histamine H2 blockers

The objective of this study was to examine whether H₂ blockers represent a major teratogenic risk. This prospective cohort study was done at the Motherisk Program, a Teratology Information Service, Toronto, Canada. The subjects included 178 women who contacted Motherisk about gestational H₂-blocker use, and 178 controls matched for maternal age, smoking, and heavy alcohol consumption. The main outcome measures were primary—major malformations, and secondary—pregnancy outcome, method of delivery, gestational age, prematurity, birthweight, small for gestational age infants, neonatal health problems, and developmental milestones. No increase in major malformations was found following first trimester exposure to H₂ blockers [2.1% vs 3.5% (controls), mean difference (95% CI) –1.4% (–5.2, +2.4)]. No other aspects of pregnancy outcome or neonatal health differed between groups. This study suggests that H₂-blocker exposure during the first trimester does not represent a major teratogenic risk.     

Effect of Maternal Asthma and Gestational Asthma Therapy on Fetal Growth

Asthma is a common chronic condition that might seriously complicate pregnancy and fetal development. This article provides a comprehensive review of the existing literature regarding the effect on fetal growth of maternal asthma and common asthma medications used during pregnancy, including short-and long-acting β ₂-agonists, inhaled and oral corticosteroids, chromones, leukotriene receptor agonists, and theophylline. Evaluated outcomes of fetal growth include low birth weight, mean birth weight, small for gestational age, birth length and head circumference, and measures of asymmetrical growth retardation. Methodological and practical considerations related to safety of asthma medications in pregnancy and management of gestational asthma are discussed.     

A Single Dose of Ethanol Suppresses Rat Embryo Development in Vivo

In humans and animal models, maternal ethanol consumption during pregnancy results in a variety of fetal defects collectively termed the fetal alcohol syndrome (FAS). Limited follow-up studies suggest that FAS children fail to achieve normal physical or mental development despite significant postnatal intervention. Although the complete FAS appears to result only when chronic, excessive alcohol consumption occurs throughout pregnancy, several investigators have suggested that ethanol consumption at intermediate levels may induce components of FAS. The defect most consistently observed in neonates exposed to ethanol is growth retardation. Even those children whose mothers consume limited amounts of ethanol during pregnancy have a significant incidence of fetal growth deficiency. We now report that a single dose of ethanol administered to female Holtzman rats within 8 hr after mating results in a dose-dependent retardation of cell division in the fertilized ova. The growth retardation is sustained up to 42 hr after the dose and the embryos of young mothers are especially sensitive to ethanol. Animals with high blood alcohol levels (<150 mg/100 ml) show a significant increase in abnormal embryo morphology. These data suggest that maternal consumption of a single dose of ethanol near the time of conception retards embryonic growth and may be detrimental to the developing organism. Further, young female rats receiving a high dose of ethanol had significantly lower uterine weights and a lower number of corpora lutea per ovary, suggesting that a single dose of ethanol has a detrimental effect on maternal reproductive ability.     

Adrenalectomy But Not Adrenal Demedullation During Pregnancy Prevents the Growth-Retarding Effects of Fetal Alcohol Exposure

Growth retardation, both in the prenatal and the early neonatal period, is a consistent feature of fetal alcohol exposure, but the mechanism by which alcohol affects growth has not been eludicated. Because other stressors–such as maternal restraint and neonatal glucocorticoid treatment–can also affect growth, we examined the effect of ethanol on pup birthweight under two experimental conditions that altered maternal adrenal function. In the first study when dams were adrenalectomized and given low replacement doses of dexamethasone, the ethanol-exposed offspring of the adrenalectomized dams had birthweights similar to those of dams maintained on regular lab chow diets. In a second study, we found that maternal adrenal demedullation did not alter the reduction in birthweight produced by fetal ethanol exposure. The results suggest that the effects of ethanol on fetal growth may be mediated in part through ethanol-induced changes in the function of the maternal adrenal cortex.