Number of axons in the corpus callosum of the Mature macaca nemestrina: increases caused by prenatal exposure to ethanol.

The effects of prenatal exposure to ethanol on the number of callosal axons were examined. Pregnant Macaca nemestrina were treated with ethanol (1.8 g/kg b.wt.) 1 day per week during the first 6 weeks (Et6) or full 24 weeks (Et24) of gestation. Control macaques were intubated with an isocaloric amount of sucrose water (Ct). The mid-sagittal area of the corpus callosum in 4- to 5-year-old offspring was examined in magnetic resonance (MR) images and in fixed brains. The number of callosal axons was determined by using electron microscopy. In both MR images and fixed brains of macaques treated with ethanol, the corpus callosum was 26% larger than in the controls. The rostral portion was particularly affected by ethanol; it was 55% larger in Et6- and Et24-treated macaques. Axonal size and myelin thickness were unaffected by ethanol, but ethanol-treated macaques had more callosal axons (13.7 x 10(7)) than did controls (9.4 x 10(7) axons). The increase in the rostral corpus callosum suggests that parietal and frontal cortices are particularly susceptible to ethanol. The altered callosal connectivity may be a component of the structural abnormalities that underlie executive processing problems associated with fetal alcohol syndrome.

Analysis of facial shape in children gestationally exposed to marijuana, alcohol, and/or cocaine.

The association between fetal marijuana and/or alcohol exposure and facial features resembling fetal alcohol syndrome was investigated in a sample of 80 children. Standardized lateral and frontal facial photographs were taken of 40 children, 5 to 7 years of age, whose mothers reported frequent use of marijuana during the first trimester of pregnancy and 40 children whose mothers reported no use of marijuana during pregnancy. The marijuana-exposed and unexposed children were group-matched on alcohol exposure prior to and during pregnancy, sex, race, and age at the time of assessment. The photographs were assessed clinically by a study staff dysmorphologist and morphometrically by computerized landmark analysis. Fetal alcohol syndrome-like facial features were not associated with prenatal marijuana exposure in this study sample. No consistent patterns of facial features were identified among the marijuana-exposed group. Maternal consumption of two or more ounces of alcohol per day, on average, in early gestation was found to be associated with fetal alcohol syndrome-like facial features identified both clinically and morphometrically. Cocaine use reported by 13 of the 80 women was independently associated with mild facial dysmorphic features of hypertelorism and midfacial flattening. The results demonstrate the usefulness of this diagnostic technique for quantifying anomalies apparently unique to fetal alcohol syndrome and for targeting clusters of anomalies in new conditions for future evaluation.

Demystified...recombinant antibodies.

Recombinant antibodies are important tools for biomedical research and are increasingly being used as clinical diagnostic/therapeutic reagents. In this article, a background to humanized antibodies is given, together with details of the generation of antibody fragments--for example, single chain Fv fragments. Phage antibody fragments are fast becoming popular and can be generated by simple established methods of affinity enrichment from libraries derived from immune cells. Phage display methodology can also be used for the affinity enrichment of existing antibody fragments to provide a reagent with a higher affinity. Here, phage antibodies are demystified to provide a greater understanding of the potential of these reagents and to engage clinicians and biomedical scientists alike to think about potential applications in pathology and clinical settings.

Outcomes of suction curettage and mifepristone abortion in the United States. A prospective comparison study.

A prospective, nonconcurrent cohort analysis of 178 mifepristone/misoprostol and 199 suction curettage abortion subjects, ages > or = 18 years, with intrauterine pregnancies < or = 63 days estimated gestational age, was conducted to compare the outcomes of suction curettage abortion to those of medical abortion. The medical abortion subjects received 600 mg of mifeprisone orally, followed by 400 micrograms of oral misoprostol 2 days later. Surgical abortion subjects underwent electronic vacuum aspiration. All subjects were followed for 2 weeks or until the absence of clinical bleeding. Outcome measures included a successful abortion (complete abortion without a surgical intervention), duration of bleeding, and morbidity. Overall, 18.3% medical and 4.7% surgical patients failed their primary procedure and received an unanticipated suction curettage (RR 3.93, 95% CI 1.87, 8.29). Four mifepristone subjects required curettage for acute bleeding, nine to manage ongoing pregnancy, and five for incomplete abortion. Fourteen mifepristone and eight surgical subjects required curettage for persistent bleeding. The median time delay for therapeutic curettage was significantly longer in the medical abortion group (35 versus 8 days; Mann-Whitney U = 17.0, p = 0.008). Medical subjects experienced significantly longer bleeding (mean difference = 9.6 days, 95% CI 6.8, 12.4). No significant change in hemoglobin occurred in either group. Mifepristone patients reported significantly greater pain (77.1% vs 10.5%; RR 7.4, 95% CI 4.7, 11.5), and nausea or vomiting (68.6% vs 0.6%; RR 117.9, 95% CI 16.7, 834.7). Women receiving mifepristone/misoprostol are more likely to require an unplanned surgical intervention than women who undergo suction curettage. They experience more discomfort with their procedure and in the follow-up interval, bleed for a longer period, and remain at risk for surgical completion curettage for several weeks.

PIP: A prospective, nonconcurrent cohort analysis was conducted to compare the outcomes of suction curettage abortion to those of medical abortion in the US. The study included 178 mifepristone/misoprostol and 199 curettage abortion subjects, ages 18 years or older, with intrauterine pregnancies of 63 or fewer days. Medical abortion subjects received 600 mg of mifepristone orally, followed by 400 mcg of oral misoprostol 2 days later. Surgical abortion subjects underwent electronic vacuum aspiration. Results showed that 18.3% of medical and 4.7% of surgical patients failed their primary procedure and received an unanticipated suction curettage. Medical subjects experienced significantly longer bleeding; however, no significant change in hemoglobin occurred in either group. While, mifepristone patients reported significantly greater pain, nausea or vomiting. Thus, women receiving mifepristone/misoprostol are more likely to require an unplanned surgical intervention than women who undergo curretage. Medical abortion patients have more discomfort, they bleed longer, and remain at risk for surgical completion curettage for several weeks.

Maternal marijuana use during lactation and infant development at one year.

Prenatal marijuana exposure is associated with adverse perinatal effects. Very little is known about the effect of postnatal marijuana exposure on infant development. Postnatal exposure can result from maternal use of marijuana during lactation. Delta-9-tetrahydrocannabinol (THC) transfers and concentrates in the mother's milk and is absorbed and metabolized by the nursing infant. The present study investigated the relationship between infant exposure to marijuana via the mother's milk and infant motor and mental development at one year of age. One hundred and thirty-six breast-fed infants were assessed at one year of age for motor and mental development. Sixty-eight infants were exposed to marijuana via the mother's milk. An additional 68 infants were matched to the marijuana-exposed infants on pre- and postpartum maternal alcohol and tobacco use. Marijuana exposure via the mother's milk during the first month postpartum appeared to be associated with a decrease in infant motor development at one year of age.

Magnetic resonance imaging and spectroscopy in fetal ethanol exposed Macaca nemestrina.

Magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS) offer noninvasive ways to observe structural and biochemical changes which might serve as valuable diagnostic markers for detecting brain damage from prenatal ethanol teratogenesis. Cranial MR imaging and spectroscopy were performed on 20 nonhuman primates (Macaca nemestrina) with known prenatal ethanol exposures and well-documented cognitive and behavioral levels of performance. The choline: creatine ratio detected by 1H-MRS in the brain increased significantly with increasing duration of in utero ethanol exposure. These signal alterations occurred in the absence of gross structural brain anomalies (detectable by MRI) and were significantly correlated with alcohol-related cognitive and behavioral dysfunction. These observations are consistent with reports of elevated choline: creatine ratios associated with various neurologic insults and disease states. The association observed between brain choline:creatine ratios and in utero ethanol exposure suggest a role for 1H-MRS in elucidating mechanisms of ethanol teratogenicity.

Characterization of anti-myosin monoclonal antibodies.

The characterization of monoclonal antibodies (MAbs) with regard to reactivity and specificity is important for the successful application as a molecular probe and/or diagnostic reagent. Furthermore, it is recognized that some monoclonal reagents perform well in some assay systems but not others. In this study, the reactivity profiles of two anti-myosin MAbs (H1 and DH2, raised against human cardiac myosin) were evaluated in enzyme-linked immunosorbent assay (ELISA), slot-blotting, and immunocytochemistry. Both antibodies performed well in slot-blotting against myosin heavy chain preparations from cardiac and skeletal muscle and from non-human sources. In general, MAb H1 demonstrated strong to moderate reactivity in all assay systems, whilst MAb DH2 faired poorly in ELISA. MAb H1 also showed reactivity to synthetic peptides of myosin, one of which possessed a motif (ERRDA, single amino acid code) that was found in other human and nonhuman myosin protein sequences that could explain its cross-reactive profile. Intriguingly, this motif was found on viral and other pathogenic agents associated with myocarditis. Hence, it is speculated that this region could give some credence to the mechanism of molecular mimicry associated with some cardiac diseases. Overall, MAb H1 may serve as a useful probe of myosin structure.

Pregnancy outcomes after weekly oral administration of ethanol during gestation in the pig-tailed macaque: comparing early gestational exposure to full gestational exposure.

An oral dose of 1.8 g/kg ethanol given once per week throughout gestation to gravid pig-tailed macaques (Macaca nemestrina) has been established previously as teratogenic. This study was designed to use this nonhuman primate model to mimic a common problematic human circumstance in which women intermittently abuse alcohol into early pregnancy, realize that they are in fact pregnant, and then want to know the chance that the conceptus is harmed. In order to evaluate this situation, gravid macaques were assigned to one of four dosing cohorts. Animals were given the 1.8 gm/kg dose of ethanol once per week for the first 3, 6, or 24 weeks (full gestation) of pregnancy. Control animals received an isocaloric, isovolemic sucrose solution once per week for 24 weeks. The pregnancies were carefully monitored and the infants were comprehensively evaluated for the first 24 months of life. This paper describes the pregnancies while subsequent papers will describe the infants. Peak plasma ethanol levels ranged from 175 to 250 mg/dl. Weekly maternal exposure to this intoxicating dose of ethanol, starting early in pregnancy, did not influence risk of pregnancy failure during the first 30 days of gestation but appeared to be associated with an increased risk of abortion occurring between gestational days 30 and 160. Of the pregnancies that were successfully carried to full term, the potentially teratogenic dose of ethanol did not alter pregnancy outcome in any clinically significant way.

A case definition and photographic screening tool for the facial phenotype of fetal alcohol syndrome.

OBJECTIVES: The purpose of this study was to demonstrate that a quantitative, multivariate case definition of the fetal alcohol syndrome (FAS) facial phenotype could be derived from photographs of individuals with FAS and to demonstrate how this case definition and photographic approach could be used to develop efficient, accurate, and precise screening tools, diagnostic aids, and possibly surveillance tools. STUDY DESIGN: Frontal facial photographs of 42 subjects (from birth to 27 years of age) with FAS were matched to 84 subjects without FAS. The study population was randomly divided in half. Group 1 was used to identify the facial features that best differentiated individuals with and without FAS. Group 2 was used for cross validation. RESULTS: In group 1, stepwise discriminant analysis identified three facial features (reduced palpebral fissure length/inner canthal distance ratio, smooth philtrum, and thin upper lip) as the cluster of features that differentiated individuals with and without FAS in groups 1 and 2 with 100% accuracy. Sensitivity and specificity were unaffected by race, gender, and age. CONCLUSIONS: The phenotypic case definition derived from photographs accurately distinguished between individuals with and without FAS, demonstrating the potential of this approach for developing screening, diagnostic, and surveillance tools. Further evaluation of the validity and generalizability of this method will be needed.

Measuring the facial phenotype of individuals with prenatal alcohol exposure: correlations with brain dysfunction.

The purpose of this report is to demonstrate how to measure the magnitude of expression of the fetal alcohol syndrome (FAS) facial phenotype using the new 4-Digit Diagnostic Code and the previously developed D-score and to demonstrate how these two measures of the FAS facial phenotype correlate with brain function and structure; correlations that fail to be identified by the older gestalt method of facial measurement. The D-score and the facial component of the 4-Digit Diagnostic Code quantitatively measure the magnitude of expression of the FAS facial phenotype using three facial features (palpebral fissure length, philtrum smoothness, and upper lip thinness). These facial measurement systems were developed by the Washington State FAS Diagnostic and Prevention Network (FAS DPN) of clinics and are used to screen and diagnose the facial component of FAS for all patients evaluated in the network of clinics (1500 to date). The 4-Digit Diagnostic Code is a comprehensive diagnostic system developed by the FAS DPN in 1997 to diagnose the full spectrum of outcomes among patients with prenatal alcohol exposure. The four digits reflect the magnitude of expression of the four key diagnostic features of FAS in the following order: (1) growth deficiency; (2) the FAS facial phenotype; (3) brain dysfunction; (4) gestational alcohol exposure. The 4-Digit Diagnostic Code was developed to overcome the subjective, highly variable gestalt method of diagnosis that has been used as the standard to date, worldwide. Prior to the development of the 4-Digit Diagnostic Code, the first 445 patients evaluated in the FAS DPN were diagnosed using the gestalt method. For research purposes, their gestalt diagnoses were transformed into 4-Digit Diagnostic Codes, presenting a unique opportunity to directly compare the two diagnostic methods. When the facial phenotype was measured using the 4-Digit Diagnostic Code or D-score, the magnitude of expression of the FAS facial phenotype was significantly correlated with structural, neurologic, and functional measures of brain damage, and the phenotype of those receiving a 4-Digit Diagnosis of FAS showed little variability. When the gestalt method of diagnosis was used, the magnitude of expression of the FAS facial phenotype did not correlate with structural, neurologic and functional measures of brain damage, and the facial phenotype of those receiving a gestalt diagnosis of FAS was highly variable. The 4-Digit Diagnostic Code and D-score thus provide more precise and accurate measures of the FAS facial phenotype and reveal important correlations with brain structure and function, suggesting that intermediate expressions of the FAS facial phenotype may serve as important risk factors for brain damage caused by prenatal alcohol exposure.

Diagnosing the full spectrum of fetal alcohol-exposed individuals: introducing the 4-digit diagnostic code.

The medical/research records of 1014 patients diagnosed at the Washington State Fetal Alcohol Syndrome (FAS) Diagnostic and Prevention Network (DPN) of clinics were used to develop a new, comprehensive, reproducible method for diagnosing the full spectrum of outcomes among patients with prenatal alcohol exposure. This new diagnostic method, called the 4-Digit Diagnostic Code, was compared to the standard gestalt method of diagnosis on the first 454 patients who had received a gestalt diagnosis of FAS, atypical FAS (AFAS) or possible fetal alcohol effect (PFAE) prior to the development of the 4-Digit Diagnostic Code. The outcomes of the patients were more accurately and comprehensively documented by the 4-Digit Diagnostic Code, because of its use of quantitative, objective measurement scales and specific case definitions. The four digits in the code reflect the magnitude of expression of the four key diagnostic features of FAS in the following order: (1) growth deficiency; (2) the FAS facial phenotype; (3) central nervous system damage/dysfunction; (4) gestational alcohol exposure. The magnitude of expression of each feature is ranked independently on a four-point Likert scale with 1 reflecting complete absence of the FAS feature and 4 reflecting a strong 'classic' presence of the FAS feature. The 4-Digit Diagnostic Code is being used effectively for diagnosis, screening, and surveillance efforts in all Washington State FAS DPN clinics.

A fetal alcohol syndrome screening tool.

The purpose of this study was to derive a multivariate, quantitative case definition of the fetal alcohol syndrome (FAS) facial phenotype from a dysmorphologist-derived gold standard and use it to develop an effective screening tool for identification of children at risk for FAS. The facial and physical features of a racially mixed group of children (0.2-10.0 years of age), evaluated by a single dysmorphologist in the University of Washington FAS Clinic, were used to determine which feature or set of features best differentiated between children with and without a diagnosis of FAS. The study population was divided into two groups balanced on gender, age at examination, race, diagnosis, and date of examination. Group 1 was used to identify the most differentiating feature(s), and group 2 was used to validate the differentiating capability of the feature(s). Group 1 included 97 children (20 with FAS and 77 without FAS). Group 2 included 97 children (19 with FAS and 78 without FAS). Discriminant analysis identified smooth philtrum, thin upper lip, and short palpebral fissures as the cluster of features that best differentiated children with and without FAS based on the discriminant function [D = 1.7953086 + 0.8116083 (thin upper lip) + 2.6411562 (smooth philtrum)-3.4073780 (% predicted right palpebral fissure length)]. Patients with a D-score > or = 1.5 were classified as at-risk for FAS (screen positive). Using this cut-off value for the D-score, children in group 1 were classified with 100% sensitivity (20 of 20 true positives) and 90.0% specificity (70 of 77 true negatives). The children in group 2 were classified with 100% sensitivity (19 of 19 true positives) and 87.3% specificity (68 of 78 true negatives). Across all 194 patients, sensitivity was 100% [95% confidence interval (97-100)] and specificity was 89% [95% confidence interval (85 to 93)]. Seventy-one percent (n = 12) of the 17 false-positives had a true classification of possible fetal alcohol effects. Sensitivity and specificity were unaffected by race, gender, and age through 10 years. The screening tool is effective at differentiating children with and without FAS as diagnosed by a single dysmorphologist (S.K.C) at the University of Washington FAS Clinic. Assessment of diagnostic interrater agreement between trained dysmorphologists and testing in other clinic populations will be needed to assess the tool's external validity.

Pregnancy outcomes after weekly oral administration of ethanol during gestation in the pig-tailed macaque (Macaca nemestrina).

Ethanol was orally administered once per week to gravid pig-tailed macaques (Macaca nemestrina) in doses of 0.3, 0.6, 1.2, 1.8, 2.5, 3.3, or 4.1 g/kg. A control group received a sucrose solution, isocaloric and isovolemic to the highest ethanol dose. Pregnancy was followed after 116 possible conceptions in 54 females. Peak plasma ethanol concentrations (PPECs) ranged from 24 +/- 6 mg/dl at the 0.3 g/kg dose to 549 +/- 71 mg/dl at the 4.1 g/kg dose. An increased rate of spontaneous abortion was related to ethanol exposure at and above 1.8 g/kg (mean PPEC = 205 mg/dl). Pregnancy failure in the first 30 days of gestation increased at doses above 2.5 g/kg. The effect on pregnancy outcome of weekly exposure to ethanol in this nonhuman primate is comparable to available data on humans. The methodology of this study represents an effective model for studying ethanol teratogenesis in a nonhuman primate.

Physical anomalies and developmental delays in nonhuman primate infants exposed to weekly doses of ethanol during gestation.

Ethanol was orally administered once per week to 54 gravid pigtailed macaques (Macaca nemestrina) in doses of 0.0, 0.3, 0.6, 1.2, 1.8, 2.5 or 4.1 gm/kg from the 1st week in gestation or in doses of 2.5, 3.3, or 4.1 gm/kg from the 5th week. Mean maternal mean peak plasma ethanol concentrations (MPPEC) ranged from 24 +/- 6 mg/dl at the 0.3 gm/kg dose to 549 +/- 71 mg/dl at the 4.1 gm/kg dose. Thirty-three viable infants were followed from birth to 6 months of age and assessed for growth, health, congenital anomalies and developmental rate. Facial anomalies, growth deficiency, or central nervous system dysfunction were found in 57% of the alcohol-exposed animals. No animal showed all the features of the human fetal alcohol syndrome. Ten of the twelve animals (83%) with mean MPPEC above 140 mg/dl had evidence of a teratogenic impact. The animals with full gestational exposure to ethanol and mean MPPEC between 140 and 249 mg/dl had much more severe and consistent cognitive abnormalities than the animals with delayed gestational exposures, even though the latter were exposed to mean MPPEC between 260 and 540 mg/dl. Conclusions from this study included: 1) ethanol-related behavioral teratogenesis occurred without accompanying physical anomalies, 2) measurable teratogenic effects from weekly exposures occurred only at intoxicating doses of ethanol, and 3) early gestational exposure to ethanol appeared to be more damaging to cognitive function than later and considerably greater alcohol exposure.

Dialysis-associated seizures in children and adolescents.

A retrospective medical chart review was conducted to document seizure occurrence in 180 children and adolescents (newborn to 22 years of age) receiving hemodialysis (HD) and/or peritoneal dialysis (PD) from January 1974 through June 1988 at Children's Hospital and Medical Center in Seattle, Washington. The purpose of the review was to identify risk factors associated with seizure activity during or up to 24 h following dialysis treatment. Seventy-eight patients received only HD, 79 received only PD and 23 received both HD and PD. Dialysis-associated seizures (DAS) were seen in 7.2% (13/180) of all dialyzed patients; 12 occurred during HD and 1 occurred during PD. Patients receiving only HD were more likely to experience DAS (7/78, 9%), than patients receiving only PD (0/79, 0%) (chi-squared = 5.5, 1 df, P = 0.02). Among the 101 patients who received HD, the risk of HD-associated seizures among those with a prior history of seizure (6/21, 29%) was significantly higher than among those with no history of seizure (6/80, 8%) (chi-squared = 5.2, 1 df, P = 0.02). Prior history of seizure did not influence the risk of seizures among patients receiving PD. These data suggest that patients receiving HD, and especially those with a prior history of seizure, should be monitored closely during dialysis and measures taken to reduce the risk of seizures.

Holoprosencephaly in a fetal macaque (Macaca nemestrina) following weekly exposure to ethanol.

Previous studies in rodents have indicated that the facial changes of fetal alcohol syndrome (FAS) closely resemble those of a mild form of holoprosencephaly. In order to examine this relationship in non-human primates, we evaluated a 133-day gestation macaque (Macaca nemestrina) with holoprosencephaly, median cleft lip and palate, and encephalocele. The mother had been given ethanol once per week (1.8 g/kg body weight) from weeks 2 to 19 postconception. Diagnosis of holoprosencephaly was made following ultrasound evaluation for polyhydramnios and delivery of the female fetus by caesarean section. Another fetus of identical age was delivered by caesarean section for use as a control. Both fetuses were studied by anthropometric, gross, radiographic, and histologic techniques. In the fetus exposed to alcohol, no extracranial anomalies were identified and the karyotype was normal. The brain was micrencephalic, with absent olfactory bulbs, tracts, optic nerves and chiasma, fused frontal lobes, and a single, dilated lateral ventricle; a parietooccipital encephalocele consisted of thin, dysplastic cortex bordering the ventricle; the cerebellum was dysplastic and superiorly displaced. Within the craniofacial complex, anophthalmia was bilateral; premaxillary components were absent, palatal shelves separate, the maxillae closeset, and the ethmoid bone small and deformed. Most of these defects are similar to those encountered in humans with holoprosencephaly and support the hypothesis of shared etiologic and pathogenetic relations between the facial anomalies of fetal alcohol syndrome and holoprosencephaly.

Morphometric analysis of Macaca nemestrina exposed to ethanol during gestation.

This study was part of a multidisciplinary investigation of the effects of gestational ethanol exposure in nonhuman primates. Thirty-one pregnant Macaca nemestrina were exposed to weekly ethanol doses of 0.0, 0.3, 0.6, 1.2, 1.8, 2.5, 3.3, or 4.1 g/kg maternal weight. Dose cohorts 0.0 through 1.8 were exposed to the initial ethanol dose within 10 days postconception. Dose cohorts 2.5 through 4.1 received their initial dose after the fifth week of gestation. Morphometric analyses performed on cranial radiographs showed that animals exposed to high doses of gestational ethanol had, on average, slightly smaller, distorted crania than control animals. A dysmorphic, flat face characteristic of fetal alcohol syndrome was recognized in one animal of the 1.8 g/kg cohort. The animal that received the highest doses of gestational ethanol was microcephalic. Similar malformations were not seen with low ethanol exposures or in controls. These data suggest a pattern of cranial distortion that may be recognizable and characteristic of ethanol teratogenesis.

Quantitative comparison of conventional spin echo and fast spin echo during brain myelination.

PURPOSE: Fast SE (FSE) sequences have largely replaced conventional SE (CSE) T2-weighted sequences in the brain and have been generally accepted as qualitatively comparable. The purpose of the present study was to subject these sequences to a quantitative comparative analysis in the brain. METHOD: A quantitative analysis of relative signal intensities of white and gray matter was performed comparing CSE and FSE T2-weighted sequences in brains of 20 children at varying stages of myelination. RESULTS AND CONCLUSION: At all ages in individual patients, white matter had less signal intensity (SI) relative to gray matter on FSE than CSE, though the relative difference in SI was small. This resulted in white matter appearing slightly more myelinated on FSE than CSE. This difference is attributed to differences in magnetization transfer. In myelinated brain (white matter hypointense to gray matter), contrast-to-noise was greater with FSE, while in unmyelinated brain, contrast-to-noise was greater with CSE.

Cognitive and behavioral deficits in nonhuman primates associated with very early embryonic binge exposures to ethanol.

This study was undertaken to evaluate teratogenesis associated with early weekly ethanol exposure followed by later gestational abstinence. Ethanol, 1.8 gm/kg, was orally administered weekly to gravid nonhuman primates (Macaca nemestrina) for the first 3, 6, or the entire 24 weeks of pregnancy. Control animals received weekly sucrose solution as did the 3- and 6-week cohort animals in subsequent weeks. Thirty-five viable infants were assessed for growth, malformations, and behavioral and cognitive dysfunction. Animals in the 6-week and 24-week cohorts were uniformly abnormal in behavior and inconsistently abnormal in physical development relative to the control animals. Animals in the 3-week cohort were equivocally normal. These results demonstrate ethanol's capacity to produce behavioral teratogenesis (brain dysfunction) in isolation from physical anomalies in the rest of the body. The results strongly suggest that binge drinking in the first 6 to 8 weeks of pregnancy (a period when women may not know that they are pregnant), followed by later gestational abstinence, is as dangerous to the fetus as exposure throughout gestation.

Fetal alcohol syndrome (FAS) primary prevention through FAS diagnosis: I. Identification of high-risk birth mothers through the diagnosis of their children.

A 5-year, fetal alcohol syndrome (FAS) primary prevention study was conducted in Washington State to: (1) assess the feasibility of using a FAS diagnostic and prevention clinic as a centre for identifying and targeting primary prevention intervention to high-risk women (namely women who had given birth to a child with FAS); (2) generate a comprehensive, lifetime profile of these women; (3) identify factors that have enhanced and/or hindered their ability to achieve abstinence. The results of this study are presented in two parts: work on objective 1 is summarized in the present paper; whereas that on objectives 2 and 3 is summarized in the accompanying paper. This project demonstrated that a multidisciplinary FAS Diagnostic and Prevention Network (FAS DPN) clinic could successfully attract and meet the diagnostic and treatment planning needs of patients presenting with prenatal alcohol exposure. One out of every three patients evaluated in the FAS DPN clinics was diagnosed with FAS or static encephalopathy/alcohol exposed. The birth mothers of one out of every three of these children diagnosed with FAS or static encephalopathy/alcohol exposed could be located and directly contacted. Half of the birth mothers directly contacted were still at risk for producing more children damaged by prenatal alcohol exposure. Thus, one out of every 18 children evaluated in the FAS DPN clinics had a birth mother who could be found and was at risk of producing more children damaged by prenatal alcohol exposure. Primary prevention programmes targeted to this high-risk population could lead to measurable, cost-effective reductions in the incidence of FAS. Using this approach, the cost of raising a child with FAS would be roughly 30 times the cost of preventing FAS in the child. The benefit to the children, their mothers, and society would be immeasurable.