Effects of gestational alcohol exposure on the fatty acid composition of umbilical cord serum in humans.

This study examined the effects of maternal periconceptional alcohol intake on polyunsaturated fatty acid (PUFA) concentrations in human neonates. The area percentage of each fatty acid in cord blood serum from 12 infants born to control women (who consumed <2 mL absolute ethanol/d) was compared with that of 9 infants born to women whose periconceptional alcohol intake averaged > or = 30mL absolute ethanol/d. Periconceptional alcohol use was associated with a 30% increase in the proportion of docosahexaenoic acid (22:6n-3) in cord blood (3.0% of total lipid in control infants compared with 3.9% in alcohol-exposed infants; P < 0.01). The rise in the proportion of 22:6n-3 was responsible for increases in the ratio of n-3 to n-6 fatty acids and the ratio of long-chain n-3 to n-6 fatty acids (P < 0.055). Examination of the lipid-class fatty acid profile indicated that serum lipid alterations were localized to the cholesterol esters; 22:6n-3 in the cholesterol esters of alcohol-exposed infants increased 54% (P < 0.011) and arachidonic acid increased 55% (P < 0. 005). The relative fatty acyl composition of maternal serum showed a significant increase in 18:0 fatty acids in the alcohol-exposed group (25%, P < 0.005) but there were no changes in the other fatty acids. The increase in the proportion of 22:6n-3 was unexpected but is consistent with the hypothesis that this essential lipid may be conserved selectively. These results imply that the lifelong neurobehavioral and sensory dysfunction in fetal alcohol syndrome and other alcohol-related neurodevelopmental disorders may be due in part to PUFA dysregulation.

Cord blood carbohydrate-deficient transferrin levels are markedly higher than maternal.

Regular, heavy alcohol intake results in transferrin that is deficient in carbohydrate moieties. Carbohydrate-deficient transferrin (CDT) has been used as a biologic marker of heavy alcohol exposure in nonpregnant humans. There have been no reports of CDT levels in pregnancy. Our objective was to determine maternal and cord blood levels of CDT. Parturients were recruited at delivery based on graded representative alcohol consumption, from abstainers to heavy drinkers, as determined by screeners skilled at eliciting drug and alcohol histories. Maternal and cord blood serum samples were obtained at delivery. A double antibody radioimmunoassay was used to determine CDT in each sample. There were 83 paired specimens analyzed by paired t tests and stepwise regression analysis. Cord blood CDT units/liter (44.0 +/- 29.5) were significantly (P < 0.0001) higher than maternal (18.4 +/- 7.0). Maternal and cord CDT did not correlate with race, perinatal risk score, gestational age at delivery, birth weight, Apgar scores, or reported alcohol intake. Maternal CDT levels had a significant negative correlation with cigarette smoking. Cord blood CDT levels are significantly higher than maternal. While regular, heavy alcohol consumption by adults results in serum transferrin deficient in carbohydrate moieties, the reason for elevated fetal CDT is unknown.

Alcohol dehydrogenase-2*3 allele protects against alcohol-related birth defects among African Americans.

Considerable variation in offspring outcome is observed after intrauterine alcohol exposure. The underlying mechanism may include genetic diversity in the enzymes responsible for alcohol metabolism. Of the known genetic polymorphisms, differences at the alcohol dehydrogenase-2 locus (ADH2) are likely most critical because the resulting enzymes are >30-fold different in their kinetic constants. To test whether differences in maternal or offspring ADH2 genotype are determinants of risk for alcohol-related birth defects, maternal-infant pairs (n = 243) were enrolled on the basis of maternal alcohol intake during pregnancy and maternal ADH2 genotype. Infant outcome was measured using the Bayley Scales of Infant Development Mental Index (MDI) at 12 months of age. Drinking during pregnancy was associated with lower MDI scores but only in the offspring of mothers without an ADH2*3 allele (P < .01, analysis of variance, post hoc). The offspring of drinking women with at least one ADH2*3 allele had MDI scores similar to those of nondrinking women of either ADH2 genotype. Lower MDI scores were associated with the three-way interaction among increasing alcohol intake and maternal and offspring absence of the ADH2*3 allele (P < .01, multiple linear regression). We suggest that the protection afforded by this allele is secondary to its encoding of the high-Km/high-Vmax ADH beta3 isoenzyme, which would provide more efficient alcohol metabolism at high blood alcohol concentrations. These observations are supportive of alcohol, rather than acetaldehyde, being the more important proximate teratogen and are the first observations of a specific genetic explanation for susceptibility differences to alcohol-related birth defects.

Maternal assessment of infant development: associations with alcohol and drug use in pregnancy.

Surveillance by parental concern has been advocated to assess whether formal child developmental testing is needed. To determine whether alcohol intake or illicit drug use in pregnancy is associated with differences in maternal perception of infant development, mothers with acknowledge alcohol and drug habits during pregnancy (N = 120) were interviewed at 11 months' postpartum, within 1 month before infant testing by use of the Bayley Scales of Infant Development. Women with heavy alcohol intake during pregnancy (> 3.5 oz absolute alcohol per week) were 15-fold more likely to overestimate their infant's mental development (P < 0.05), whereas mothers using illicit drugs were 4-fold more likely to overestimate their infant's physical development (P = 0.02). Given the frequent denial of substance abuse, we suggest that health care providers be cautious in accepting a lack of parental concern about a child's development and rely more heavily on formal testing, particularly in high-risk populations.

New evidence for neurobehavioral effects of in utero cocaine exposure.

Most studies of prenatal cocaine exposure have found gestational age or intrauterine growth deficits but few, if any, cognitive effects. In a large, well-controlled study we detected cognitive deficits in relation to heavy cocaine exposure. These findings demonstrate that prenatal exposure to cocaine at sufficiently high doses early in pregnancy has the potential to produce cognitive changes in infants and that more focused, narrow-band tests may be necessary to detect these subtle neurobehavioral effects. A total of 464 inner-city, black infants whose mothers were recruited prenatally on the basis of pregnancy alcohol and cocaine use were tested at 6.5, 12, and 13 months of age. Standard analyses, based on presence or absence of cocaine use during pregnancy, confirmed effects on gestational age but failed to detect cognitive effects. A new approach to identifying heavy users found that heavy exposure early in pregnancy was related to faster responsiveness on an infant visual expectancy test but to poorer recognition memory and information processing, deficits consistent with prior human and animal findings. These persistent neurobehavioral effects of heavy prenatal cocaine exposure appear to be direct effects of exposure and independent of effects on gestational age.

Detecting risk drinking during pregnancy: a comparison of four screening questionnaires.

OBJECTIVES: This study investigated the efficacy of screening for risk drinking during pregnancy with two brief questionnaires, TWEAK and T-ACE. Both include an assessment of tolerance based on the number of drinks women report they can hold. METHODS: Subjects were disadvantaged African-American obstetric patients in Detroit, Mich. Traditional alcoholism screens (Michigan Alcohol Screening Test [MAST], CAGE) and the tolerance question were administered (n = 2717); TWEAK and T-ACE were constructed from tolerance and embedded MAST and CAGE items. In a separate sample (n = 1420), only the T-ACE was administered. Periconceptional risk drinking was the gold standard. Screen evaluations were based on receiver-operating characteristic analyses. RESULTS: At the cutpoint of 2, sensitivity/specificity for embedded screens were 91/77 for TWEAK and 88/79 for T-ACE; comparable values for T-ACE alone were 67/86. TWEAK and T-ACE screened more effectively than CAGE or MAST. CONCLUSIONS: Embedded versions of TWEAK and T-ACE were both highly sensitive to periconceptional risk drinking in this population. Administering T-ACE alone reduced its sensitivity; this suggests that MAST and CAGE administration improves its performance.

Has awareness of the alcohol warning label reached its upper limit?

Has awareness of the alcoholic beverage warning label reached its maximum? This study tracks changes in the level of awareness among a sample of 7334 inner-city African-American gravidas seeking prenatal care between May 1989 and June 1993. Previously, we found that a significant increase in awareness of the warning label occurred in March 1990. In the current analysis over a 50-month period, the level of awareness continued to increase through December 1992 and then leveled off, suggesting a negatively accelerated growth function. The logistic function fitted to the awareness curve predicts that the upper limit of awareness in this population has been reached (the predicted upper limit being 81.5%). In addition a logit regression analysis showed that women who did not know about the warning label were more likely to be over 29 years of age. Heavier drinkers were 1.25 times more likely to be aware of the label. Among those drinkers who were not aware of the label, 30% drank at both conception and antenally, thus putting their fetus at high risk for alcohol-related birth defects.

Heeding the alcoholic beverage warning label during pregnancy: multiparae versus nulliparae.

OBJECTIVE: We compared the impact of the Federal Alcoholic Beverage Warning Label on multiparae (women with at least one previous live birth) and nulliparae (women with no previous live births). The label, implemented on November 18, 1989, urges women not to drink during pregnancy because of the risk of birth defects. If multiparae drank during prior pregnancies, delivering apparently normal babies, we hypothesized that the warning might be less salient for them. METHOD: We studied 17,456 inner city black gravidas seen between September 1986 and September 1993 at one antenatal clinic. Time series analysis (ARIMA) examined trends in monthly means of antenatal drinking scores (alcohol consumption adjusted for weeks' gestation, age, parity and periconceptional drinking). RESULTS: For nulliparae (n = 7,349), reported drinking began to show a significant decline in June 1990, 7 months after the implementation of the warning label (t = 2.00, p < .04). In contrast, multiparae (n = 10,107) showed no change in reported drinking (t = 1.23) postlabel. CONCLUSIONS: Given previous results that multiparae drink more and that heavier drinkers are ignoring the warning label, these data are very distressing and suggests the importance of targeting multiparae for intensive prevention efforts.

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)

Screening for pregnancy risk-drinking.

The efficacy of alcohol screening questionnaires, the TWEAK, T-ACE, NET, MAST, and CAGE, in detecting periconceptional risk-drinking, > or = 1 oz absolute alcohol/day, was investigated in 4743 African-American women attending an inner-city prenatal clinic who had reported ever drinking. Sensitivity, specificity, positive predictive value, efficiency, follow-up rates, and receiver operating characteristics of the questionnaires were examined to compare the overall effectiveness of the questionnaires and their performance at cut-points defining positive scores ranging from 1 to 3. Relatively little difference between TWEAK, T-ACE, and MAST was seen in the receiver operating characteristic accuracy indices; NET and CAGE lagged behind. Sensitivity/specificity scores for the two questionnaires most sensitive at cut-point 1 were TWEAK (87/72) and T-ACE (83/75). At cut-point 2, sensitivity was optimized with respect to specificity; TWEAK (79/83) was significantly more sensitive than T-ACE (70/85; p = 0.002). At cut-point 3, the two most sensitive tests were MAST (61/92) and TWEAK (59/94). In general, measures of merit were not greatly affected by the time between conception and the administration of the screens. Screening was most sensitive for women interviewed during the first 15 weeks of pregnancy; risk-drinkers tended to delay entry into prenatal care, increasing positive predictive values associated with screening later in pregnancy. This study confirms the utility, when screening for risk-drinking during pregnancy, of brief questionnaires that assess alcohol intake indirectly by asking women about their tolerance to alcohol's effects, psychological consequences of drinking, and significant others' concern about their drinking. It validates T-ACE and provides preliminary data indicating that TWEAK may outperform T-ACE.

Effects of alcohol use, smoking, and illicit drug use on fetal growth in black infants.

STUDY OBJECTIVES: To compare the effects of prenatal exposure to alcohol, smoking, and illicit drugs on birth size. DESIGN: Prospective, longitudinal correlational study, with statistical control for confounding. PARTICIPANTS: Four hundred seventeen black infants. Mothers recruited at first prenatal clinic visit on the basis of moderate-to-heavy use of alcohol or cocaine or both, plus a 5% random sample of lower-level drinkers and abstainers. MAIN RESULTS: Alcohol, smoking, opiates, and cocaine were each correlated with smaller birth weight, length, and head circumference (median r = -0.21; p < 0.001). However, when all four substances, gestational age, and six covariates were controlled statistically, birth weight related only to alcohol and smoking (p < 0.05), length only to alcohol (p < 0.05), and head circumference only to opiates (p < 0.01). Although smoking affected birth weight at all levels of exposure, a larger deficit was seen in relation to heavy drinking (509 gm) than to heavy smoking (269 gm). Alcohol and smoking did not affect birth size synergistically, and their effects were seen primarily in infants of women more than 30 years of age. CONCLUSIONS: The association of reduced birth weight and length with illicit drug use may be a consequence of simultaneous exposure of the fetus to alcohol and smoking. Opiate exposure is specifically related to reduced head circumference, and the effect of cocaine on birth size is primarily an indirect consequence of shorter gestation and poorer maternal nutrition.

Prenatal alcohol exposure and infant information processing ability.

403 black, inner-city infants born to women recruited prenatally on the basis of their alcohol consumption during pregnancy were assessed on a battery focusing on information processing and complexity of play. Prenatal alcohol exposure was not related to visual recognition memory or cross-modal transfer of information but was associated with longer fixation duration, a measure indicative of slower, less efficient information processing; lower scores on elicited play; and longer periods of toy exploration, possibly also due to slower cognitive processing. The effects on processing speed and elicited play were dose-dependent and not attributable to maternal depression, parental intellectual stimulation, other prenatal drug exposure, or postpartum maternal drinking. The processing speed deficit is consistent with deficits in older children prenatally exposed to alcohol; the present study is the first to identify slower cognitive processing in infancy and in tasks not dependent on motoric proficiency.

A time series analysis of the impact of the alcohol warning label on antenatal drinking.

In a sample of over 12,000 African-American gravidas, we tested the hypothesis that the Federal Beverage Labeling Act of 1988 has decreased antenatal drinking. Results of time series analysis indicated a 7-month lag in the impact of the alcohol warning label. Controlling for population changes, antenatal drinking began to fall as of June 1990. However, this decrease was small in size and did not impact on the heaviest drinkers. Seasonal trends in drinking were also detected, with peaks around the end of the year and the summer.

The alcohol beverage warning label: when did knowledge increase?

This article presents data on the awareness of the alcohol beverage warning label among a sample of 5,169 inner city African-American gravidas seeking prenatal care. While the label law was implemented in November 1989, a significant increase in knowledge of the label did not occur until March 1990. Women who predominantly consumed wine coolers and beer, and those under age 30 were more likely to know about the label than their counterparts.

Teratogenic effects of alcohol on infant development.

Results of previous studies of effects of drinking during pregnancy on standardized tests of infant development have varied, depending on level of exposure. This study of 382 Black, inner city infants confirmed effects of moderate-to-heavy prenatal alcohol exposure on Bayley Scale performance originally observed in a White, middle class cohort. Effects of second and third trimester drinking were as strong or stronger than those of drinking at the time of conception. New methods for reducing the Bayley Scale data suggested specific deficits relating to emergence of the ability to imitate modeled behavior and the development of standing and walking. The incidence of very poor performance (bottom 10th percentile) on the Bayley Mental Development Index more than doubled in children whose mothers averaged at least 0.5 oz absolute alcohol per day during pregnancy, indicating that this exposure has a clinically meaningful impact at markedly lower levels than those associated with full fetal alcohol syndrome. Clinically meaningful effects on the Psychomotor Development Index, by contrast, were seen only in the infants of heavy drinking mothers with overt symptomatology of alcohol abuse. Adverse effects on Bayley Scale performance were more prevalent in the infants of women more than 30 years of age.

Factors influencing fine-needle aspiration cytology in the management of recurrent gynecologic malignancies.

Over a period of 6.5 years (January 1983 through August 1989) 124 fine-needle aspirations (FNAs) were performed on 95 patients with prior documented primary malignancies of the cervix, ovary, endometrium, and vulva. The significance of clinicopathologic factors which influenced the FNA results was analyzed by statistical methods. The factors studied included the initial patient clinical stage, the time interval between staging and disease recurrence, the treatment modalities, the neoplasm type, the aspiration site, the target lesion size, and the type of radiologic guidance. Primary aspiration sites were pelvic wall and organs (40%), lymph nodes (36%), and liver (21%); 64% were positive, 5% suspicious, 15% negative, and 16% unsatisfactory. The specificity was 100%; sensitivity, 96.3%; predictive value of a positive test, 100%; and predictive value of a negative test, 84.2%. Statistically significant clinicopathologic factors which influenced the FNA results included the target lesion size (P = 0.026) and the aspiration site (P = 0.033). The primary neoplasm type, the time interval between staging and disease recurrence, the initial patient clinical stage, the treatment modalities, and the type of radiologic guidance were not statistically significant. FNA is a reliable procedure in the management of gynecologic malignancy and its results are influenced by clinicopathologic factors.

Maternal recall of alcohol, cocaine, and marijuana use during pregnancy.

Alcohol, cocaine, and marijuana use during pregnancy was reported antenatally and at 13 months postpartum by 361 black inner city mothers. The two reports were moderately related for all three substances, but levels reported retrospectively were substantially higher. MAST scores did not differ for the two interviews. Most of the correlations of the antenatal and retrospective reports with maternal and infant characteristics were similar in magnitude; those that differed were somewhat stronger for the antenatal measures. Although the retrospective reports may provide a better indication of mean levels of fetal exposure, they may be less precise in rank ordering among individuals for purposes of correlational analysis. Women with higher MAST scores were particularly prone to report higher levels of both alcohol and cocaine when interviewed retrospectively, and more severely depressed mothers were more likely to report higher levels retrospectively for all three substances. These data suggest that women reporting more than 1.3 drinks/week antenatally (AA/day greater than 0.1) may actually be drinking at levels at risk for alcohol-related birth defects.

The clinical utility of maternal body mass index in pregnancy.

To describe maternal body mass index and to compare the use of maternal weight and body mass index for risk assessment at the initial prenatal visit, 6270 gravid women who were consecutively delivered of infants were studied. Body mass index increased with advancing maternal age, parity, and advancing gestational age and was significantly greater in black women than in nonblack women. Risks for the development of adverse outcome associated with maternal obesity, including development of gestational diabetes, preeclampsia, fetal macrosomia, and shoulder dystocia, were comparably predicted by either maternal weight or body mass index greater than 90th percentile. Maternal weight was as predictive of preeclampsia, macrosomia, and shoulder dystocia as was body mass index when these factors were analyzed as continuous variables, whereas increasing body mass index was more predictive of gestational diabetes. The prediction of factors associated with low maternal weights, small-for-gestational-age birth, prematurity, low birth weight, and perinatal death was equivalent for maternal weight and body mass index that was less than 10th percentile. This study indicates that in the initial risk assessment of outcomes related to maternal weight, the calculation of maternal body mass index offers no advantage over simply weighing the patient. This finding contrasts with results in nonpregnant women.

Morphometry of the neonatal fetal alcohol syndrome face from 'snapshots'.

Recognition of alcohol-related birth defects is less successful in the neonate than in older children. Clarren et al. (1987) were able to describe the geometry of the FAS face at age 7. To define neonatal facial features of FAS, 3 reference points were used to map 7 frontal and 7 profile landmarks coded as standardized cartesian coordinates. These landmarks were digitized from snapshots of 21 neonates, prospectively diagnosed as FAS blinded for prenatal alcohol exposure, and 76 non-FAS controls. In the controls, race was found to be a significant determinant of landmarks, as expected. Using discriminant analysis and controlling for race, the FAS face was characterized by landmark measurements which correspond to short palpebral fissure, scooping out of the nasal bridge and thin vermilion [F(4,71)-7.8, r sq-30%, p < .01]. Jackknifed sensitivity was 75%, specificity, 79%. These findings suggest that FAS-defining features can be quantified in the neonate via computer-based screening of infants from at-risk pregnancies.