A prospective cohort study of the prevalence of growth, facial, and central nervous system abnormalities in children with heavy prenatal alcohol exposure.

BACKGROUND: Most children who are exposed to large quantities of alcohol in utero do not develop fetal alcohol syndrome (FAS). Population-based prospective data on the risk of developing components of fetal alcohol spectrum disorders (FASD), however, are limited. METHODS: This was a prospective cohort study of 9,628 women screened during their first prenatal appointment in Chile, which identified 101 who consumed at least 4 drinks/d (exposed) matched with 101 women with no reported alcohol consumption during pregnancy (unexposed). Detailed alcohol consumption data were collected during the pregnancy. Children were evaluated up to 8.5 years of age by clinicians masked to exposure status. RESULTS: One or more functional central nervous system abnormalities were present in 44.0% (22/50) of the exposed children compared to 13.6% (6/44) of the unexposed (p = 0.002). Growth restriction was present in 27.2% (25/92) of the exposed and 12.5% (12/96) of the unexposed (p = 0.02). Abnormal facial features were present in 17.3% (14/81) of the exposed children compared to 1.1% (1/89) of the unexposed children (p = 0.0002) by direct examination. Of the 59 exposed children with data available to detect at least 1 abnormality, 12 (20.3%) had no abnormalities. Binge drinking from conception to recognition of pregnancy (OR = 1.48 per day, 95% CI: 1.15 to 1.91, p = 0.002) and after recognition of pregnancy (OR= 1.41 per day, 95% CI: 1.01 to 1.95, p = 0.04) and total number of drinks consumed per week from conception to recognition of pregnancy (OR = 1.02 per drink, 95% CI: 1.01 to 1.04, p = 0.0009) were significantly associated with abnormal child outcome. CONCLUSIONS: After exposure to heavy alcohol consumption during pregnancy, 80% of children had 1 or more abnormalities associated with alcohol exposure. Patterns of alcohol use that posed the greatest risk of adverse outcomes were binge drinking and high total weekly intake. Functional neurologic impairment occurred most frequently and may be the only sign to alert physicians to prenatal alcohol exposure.

Heavy prenatal alcohol exposure and risk of stillbirth and preterm delivery.

We prospectively identified 96 women consuming at least 4 drinks/day during pregnancy by screening 9628 pregnant women. In these women with heavy prenatal alcohol use, there were three stillbirths and one preterm delivery; 98 matched nondrinking women had no stillbirths and two preterm births. Preterm rates did not differ significantly. The stillbirth rate was higher in the exposed group (p = 0.06). Additional investigation showed the stillbirth rate in the exposed population (3.1%) was significantly higher (p = 0.019) than the reported Chilean population rate (0.45%). Our data suggest that heavy alcohol consumption may increase the risk for stillbirth but not preterm delivery.

Effects of prenatal ethanol exposure on postnatal growth and the insulin-like growth factor axis.

AIMS: To study the effect of in-utero alcohol exposure on the insulin-like growth factor axis (IGF) and leptin during infancy and childhood, considering that exposed children may exhibit pre- and postnatal growth retardation. METHODS: We prospectively identified heavily drinking pregnant women who consumed on average 4 or more drinks of ethanol per day (≥ 48 g/day) and assessed growth in 69 of their offspring and an unexposed control group of 83 children, measuring serum IGF-I (radioimmunoassay), IGF-II (immunoradiometric assay, IRMA), insulin-like growth factor-binding protein 3 (IGFBP-3) (IRMA) and leptin (IRMA) at 1 month and 1, 2, 3, 4, and 5 years of age. RESULTS: IGF-II levels increased with age in both groups, but the rate of increase was significantly higher in exposed children, and levels were significantly higher in ethanol-exposed children at 3, 4, and 5 years of age. In exposed children, IGF-I levels were higher at 3 and 4 years and leptin levels were significantly lower at 1 and 2 years. Exposed subjects showed a much lower correlation between IGF-I and growth parameters than unexposed subjects. CONCLUSION: Exposure to ethanol during pregnancy increases IGF-I and IGF-II and decreases leptin during early childhood. The increase in serum IGF-II concentrations in ethanol-exposed children suggests that this hormone should be explored as a potential marker for prenatal alcohol exposure.

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 > or =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 F2alpha, and of the vasoactive prostaglandin metabolites, 2,3-dinor-6-keto-prostaglandin F1alpha (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 F2alpha 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 F1alpha (1.03 vs. 1.17 ng/mg creatinine, respectively, 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.

Eye malformations in children with heavy alcohol exposure in utero.

OBJECTIVE: To determine whether children who do not develop fetal alcohol syndrome (FAS) despite heavy alcohol exposure are at risk for eye abnormalities. STUDY DESIGN: We screened 9628 pregnant women and identified 101 women who were drinking >/= 2 oz of absolute alcohol per day and 101 nondrinking control women. We followed 43 exposed and 55 control offspring between age 4 and 9 years, performing masked standardized ophthalomologic examinations. RESULTS: The groups did not differ in their rates of impaired visual acuity, refractory errors, ptosis, epicanthal folds, or short palpebral fissures. Biomicroscopy examination was normal in all exposed subjects; cataracts were detected in 2 control subjects (4%) but in no exposed subjects. Arterial tortuosity was seen in 7 exposed subjects (16%) and in 8 control subjects (15%). Optic nerve hypoplasia was not detected in any subject. CONCLUSIONS: Previous research has found that children with FAS have a high incidence of serious ophthalmologic defects; our data indicate that the risk is limited to children with FAS and does not extend to children exposed to high levels of alcohol prenatally who do not develop FAS. Eye examinations are unlikely to clarify the diagnosis in children suspected of having alcohol-related damage.

Prospective identification of pregnant women drinking four or more standard drinks (> or = 48 g) of alcohol per day.

We aimed to identify drinking rates in a prospectively identified cohort of pregnant women, and subsequently, to identify the drinkers of 48 g or more alcohol/day among them, by using complementary methods for verifying self-reported drinking habits. A research team of social workers and health professionals at the Maipú Clinic, located in a lower middle class neighborhood of Santiago, Chile, conducted interviews of women attending a prenatal clinic between August 1995 and July 2000. Women whose interview responses met predefined criteria (identified in the text) were further evaluated by home visits. We interviewed 9,628 of 10,917 (88%) women receiving prenatal care. By initial interview, 42.6% of women reported no drinking, 57.4% some alcohol consumption, and 3.7% consuming at least one standard drink (15 mL of absolute alcohol) per day. Of the 887 women who had home visits, 101 were identified as consuming on average at least 4 drinks/day (48 g). To determine the best home visit questionnaire items for identifying those drinking at least 4 drinks per day, 48 women who openly admitted drinking this amount were compared with 786 women who were not considered drinkers after the home visit. The 48 self-reported 48 g/day drinkers were significantly more likely to get tipsy when drinking before (p = 0.01) or during (p < 0.0001) pregnancy, to have started drinking at a younger age (p = 0.007), or to exhibit signs of low self-esteem (p < 0.0001), sleep or appetite problems (p < 0.0001), bad interpersonal relationships (p < 0.0001) or having family members with fetal alcohol syndrome features (p < 0.009). In conclusion, using complementary methods of alcohol misuse ascertainment during pregnancy, we found that at least 1% of pregnant women in a Santiago, Chile, clinic population were drinking at levels that are clearly dangerous to the fetus (48 g/day or more). We identified specific interview questions that may help screen for alcohol use of 48 g/day or more in pregnant women.

Peripheral nerve conduction abnormalities in children exposed to alcohol in utero.

OBJECTIVE: We performed a longitudinal study of nerve conduction velocity to determine the effect of prenatal alcohol exposure on the peripheral nervous system. Study design We studied 17 children exposed to >2 oz of absolute alcohol/day prenatally and 13 unexposed children, identified prospectively from a cohort of pregnant women screened during prenatal care. Nerve conduction assessment was done on the median, ulnar, peroneal and tibial nerves during the newborn period and between 12 and 14 months of age. RESULTS: At both assessments the alcohol-exposed subjects had significantly slower ulnar motor nerve velocity (P=.007), smaller proximal (P=.018) and distal amplitude (P=.051). They also showed reduced tibial nerve velocity (P=.06) and a decrease in distal amplitude. CONCLUSIONS: This study demonstrates that prenatal alcohol exposure is associated with abnormalities in nerve electrical properties, and that the pattern is different from that seen in adults. Electrophysiologic abnormalities in peripheral nerves should be added to the problems found in children of alcohol abusing mothers.