Hospitalizations and mortality among patients with fetal alcohol spectrum disorders: a prospective study.

With nearly 10% of women consuming alcohol during pregnancy, fetal alcohol spectrum disorders (FASDs) are becoming an increasing concern for clinicians and policymakers interested in the field of healthcare. Known as the range of mental and/or physical disabilities that occur among individuals with prenatal alcohol exposure, FASDs can result in dysmorphic features, problems with physical growth, neurobehavioral and cognitive problems that not only increase risk of various diseases, but also premature mortality. We investigated whether the diagnosis of FASDs result in increased risk of hospitalizations and mortality, with respect to FASD domains and relative diseases, when age effects are controlled for. The data for this study was taken from the National Health Insurance Service - National Sample Cohort (NHIS-NSC) between 2003 and 2013. The population attributable risk (PAR) statistic was used to estimate the percentage of hospitalizations and mortality attributable to FASDs and other factors. A time-dependent Cox proportional hazards model with age of diagnosis as the time-scale was employed to calculate adjusted hazard ratios and 95% CIs for hospitalizations and mortality among FASD populations compared to their general population peers. Among the 3,103 FASD cases, 27.5% experienced hospitalizations and 12.5% died. Overall, FASDs accounted for 853 FASD-attributable hospitalizations (51.0% of all hospitalizations in the study population) and 387 mortality events (34.5% of all deaths in the study population). 20.52% of hospitalizations and 21.35% of mortalities were attributable to FASDs in this population. Compared to the control group, FASD patients had a 1.25-fold (HR: 1.25, 95% CI: 1.05-1.49, p = 0.0114) increased risk of hospitalizations and a 1.33-fold (HR: 1.33, 95% CI: 1.07-1.67, p = 0.0118) increased risk of all-cause mortality. The most common cause for hospitalization was diseases of the nervous system, which accounted for 450 FASD-attributable hospitalizations (96.2% of all nervous system hospitalizations in the study population). In fact, FASD patients were 52 times more likely to be hospitalized for nervous system diseases than their peers (HR: 51.78, 95% CI: 29.09-92.17, p < .0001). The most common cause for mortality was neoplasms, which accounted for 94 FASD-attributable deaths (28.7% of all neoplasm deaths in the study population). However, FASD patients did not have increased risk of neoplasm mortality than the general population (HR: 0.88, 95% CI: 0.59-1.32, p < .0001). Overall, this study found that individuals diagnosed with FASDs have increased risk of both hospitalizations and mortality, compared to their general population peers. This is particularly so for diseases of the nervous system, which showed a 52-fold increase in hospitalizations and four-fold increase in mortality for FASD patients in our study. Likewise, while the association between FASDs and neoplasm mortality was not significant in our investigation, more attention by neurologists and related healthcare providers regarding the link between these two factors is necessary.Trial Registration: Institutional Review Board of Yonsei University's Health System: Y-2019-0174.

Life Expectancy of People with Fetal Alcohol Syndrome.

OBJECTIVES: To estimate the life expectancy and specify the causes of death among people with fetal alcohol syndrome (FAS). METHODS: Included were all patients recorded in Alberta provincial databases of inpatients, outpatients, or practitioner claims from 2003 to 2012. People with FAS were identified by ICD-9 code 760.71 and ICD-10 codes Q86.0 and P04.3, and were linked to the Vital Statistics Death Registry to get information about mortality. Life expectancy was estimated by using the life table template developed in the United Kingdom, which is recommended for estimating life expectancy in small areas or populations. RESULTS: The life expectancy at birth of people with FAS was 34 years (95% confidence interval: 31 to 37 years), which was about 42% of that of the general population. The leading causes of death for people with FAS were "external causes" (44%), which include suicide (15%), accidents (14%), poisoning by illegal drugs or alcohol (7%), and other external causes (7%). Other common causes of death were diseases of the nervous and respiratory systems (8% each), diseases of the digestive system (7%), congenital malformations (7%), mental and behavioural disorders (4%), and diseases of the circulatory system (4%). CONCLUSION: The life expectancy of people with FAS is considerably lower than that of the general population. As the cause of FAS is known and preventable, more attention devoted to the prevention of FAS is urgently needed.

Trastornos del espectro alcohólico fetal: biomarcadores del consumo de etanol durante la gestación / Fetal alcohol spectrum disorders: biomarkers of ethanol consumption during pregnancy / Perturbações do espectro do alcoolismo fetal: biomarcadores de consumo de etanol durante a gravidez

El consumo de alcohol durante la gestación está asociado con un amplio espectro de efectos adversos conocidos como trastornos del espectro alcohólico fetal (TEAF). Así es como a través del dosaje de los esteres etílicos de ácidos grasos (FAEEs) en meconio, como biomarcadores de exposición prenatal al consumo de etanol, nos brinda una herramienta importantísima en el screening de los recién nacidos, facilitando la confi rmación del diagnóstico y la intervención clínica adecuada en los individuos afectados por esta problemática con una mejora en las expectativas y calidad de vida. El síndrome alcohólico fetal (SAF) representa el clásico síndrome y la manifestación más grave inducido por el alcohol de forma repetida durante el embarazo. Dado el carácter heterogéneo de las alteraciones clínicas presentes en los recién nacidos expuestos a etanol, la mayoría de los cuales no son específi cos, conlleva a un diagnóstico del TEAF extremadamente difícil.

Alcohol consumption during pregnancy is associated with a wide range of adverse effects known as fetal alcohol spectrum disorders (FASDs). Through the measurement of Fatty Acid Ethyl Esters (FAEEs) in meconium, as biomarkers of prenatal alcohol exposure, we have a very important tool in the screening of newborns, facilitating the confi rmation of diagnosis and adequate clinical intervention in individuals affected by this problem with improvements in life quality and expectancy. Fetal Alcohol Syndrome (FAS) represents the classic syndrome and the most serious condition is caused by repetitive alcohol consumption during pregnancy. Due to the heterogeneous characteristics of clinical alterations of newborns exposed to ethanol, most of which are not specifi c, diagnosis of FASDs is extremely diffi cult.

O consumo de álcool durante a gravidez é associado a um amplo espectro de efeitos adversos conhecidos, tais como transtornos do espectro do alcoolismo fetal (TEAF). É assim como através da dosagem dos ésteres etílicos de ácidos graxos (FAEEs) em mecô- nio, como biomarcadores de exposição pré-natal ao consumo de etanol, fornece uma ferramenta importantíssima na triagem de recém-nascidos, aprimorando a confi rmação do diagnóstico e a intervenção clínica adequada em indivíduos afectados por este problema com uma melhoria das expectativas e qualidade de vida. Síndrome alcoólica fetal (FAS) representa a síndrome clássica e a mais grave manifestação induzida frequentemente pelo álcool durante a gravidez. Dada a heterogeneidade das alterações clínicas em recémnascidos expostos ao etanol, a maioria das quais são não-específi cas, esta situação gera um diagnóstico de TEAF extremamente difícil.

The cost of lost productivity due to fetal alcohol spectrum disorder-related premature mortality.

BACKGROUND: Individuals with Fetal Alcohol Spectrum Disorder (FASD) have increased mortality as compared to the general population. OBJECTIVES: To estimate the productivity losses due to premature mortality of individuals with FASD in Canada in 2011. METHODS: A demographic approach with a counterfactual scenario in which nobody in Canada is born with FASD was used. Population estimates were calculated using data on the labour force, unemployment rate, and average weekly wage obtained from Statistics Canada. The number of FASD-related deaths, coded in the International Classification of Diseases, version 10, was estimated based on data from Statistics Canada and pooled prevalence estimates of the major disease conditions associated with FASD were obtained from a meta-analysis. The estimates of FASD-related mortality rates served as a basis for the length of working life span estimation. Once the number of working years lost to premature deaths was derived, productivity losses were computed. RESULTS: It was estimated that in total 327 individuals with FASD aged 20 to 69 (almost twice as many men as women) died in Canada in 2011. As a result, there were 2,877 years of potential employment lost, which translated to a loss ranging from $88 million to $126 million. This amount represents the increase in national income, had there been no premature mortality from FASD and the workers with FASD had been typical members of the labour force (without compromised productivity due to FASD). CONCLUSIONS: The estimates of productivity losses further reinforce the value of FASD prevention as a primary strategy.

Health care burden and cost associated with fetal alcohol syndrome: based on official Canadian data.

BACKGROUND: Fetal Alcohol Spectrum Disorder (FASD) is a group of disorders caused by prenatal alcohol exposure. From this group, Fetal Alcohol Syndrome (FAS) is the only disorder coded in the International Classification of Diseases, version 10 (ICD-10). This coding was used to gain an understanding on the health care utilization and the mortality rate for individuals diagnosed with FAS, as well as to estimate the associated health care costs in Canada for the most recent available fiscal year (2008-2009). METHODS: Health care utilization data associated with a diagnosis of FAS were directly obtained from the Canadian Institute for Health Information (CIHI). Mortality data associated with a diagnosis of FAS were obtained from Statistics Canada. RESULTS: The total direct health care cost of acute care, psychiatric care, day surgery, and emergency department services associated with FAS in Canada in 2008-2009, based on the official CIHI data, was about $6.7 million. The vast majority of the most responsible diagnoses, which account for the majority of a patient's length of stay in hospital, fall within the ICD-10 category Mental and Behavioural Disorders (F00-F99). It was evident that the burden and cost of acute care hospitalizations due to FAS is increasing -1.6 times greater in 2008-2009, compared to 2002-2003. The mortality data due to FAS, obtained from Statistics Canada (2000-2008), may be underreported, and are likely invalid. DISCUSSION: The official data on the utilization of health care services by individuals diagnosed with FAS are likely to be underreported and therefore, the reported cost figures are most likely underestimated. The quantification of the health care costs associated with FAS is crucial for policy developers and decision makers alike, of the impact of prenatal alcohol exposure, with the ultimate goal of initiating preventive interventions to address FASD.

Síndrome alcohólico fetal / Fetal Alcohol Syndrome

Recientemente se ha comentado mucho en la opinión pública el nivel del alcohol permitido legalmente, e incluso ha sido motivo de modificaciones en nuestra ley de tránsito, y es que el alcohol se ha convertido en la droga m s usada en el mundo, la cual genera problemas de tipo social, psicológico y de salud pública. El consumo de alcohol durante el embarazo puede causar defectos en varios órganos y sistemas del organismo, sobre todo si la madre lo ingiere en grandes cantidades, pero no está  demostrado que beber pocas cantidades del mismo sea inocuo. Los efectos que el consumo del mismo le produce a los embriones ha sido demostrado en la literatura desde 1973, sin embargo su uso y abuso siguen tan altos, como alta es la cantidad de ni¤os que nacen con síndrome alcohólico fetal cada día...

Alcohol drinking pattern during pregnancy and risk of infant mortality.

BACKGROUND: The safety of small amounts of alcohol drinking and occasional binge-level drinking during pregnancy remains unsettled. We examined the association of maternal average alcohol intake and binge drinking (>or=5 drinks per sitting) with infant mortality, both in the neonatal and postneonatal period. METHODS: Participants were 79,216 mothers who were enrolled in the Danish National Birth Cohort in 1996-2002, gave birth to a live-born singleton, and provided information while they were pregnant on alcohol consumption during pregnancy. Information on infant mortality and causes of death was obtained from national registries and medical records. RESULTS: During the first year of life, 279 children (0.35%) died, 204 during the neonatal period. Infant mortality was not associated with alcohol drinking, even at a consumption level of either 4+ drinks per week or 3+ occasions of binge drinking. Postneonatal mortality was associated with an intake of 4+ drinks per week (hazard ratio = 3.56 [95% confidence interval = 1.15-8.43]) and with 3+ binge episodes (2.69 [1.27-5.69]). When restricting analyses to term births, both infant mortality and postneonatal mortality were associated with a weekly average intake of 4+ drinks or 3+ binge episodes. CONCLUSIONS: Among term infants, intake of at least 4 drinks of alcohol per week or binging on 3 or more occasions during pregnancy are associated with an increased risk of infant mortality, especially during the postneonatal period.

Mortality rates in subjects with fetal alcohol spectrum disorders and their siblings.

BACKGROUND: Our objective was to estimate the mortality rate in subjects with fetal alcohol spectrum disorders (FASD) and their siblings whose FASD status was unknown. METHODS: We used the state FASD Registry to link subjects with FASD to a North Dakota birth certificate. We were able to link 304 of 486 cases (63%). We used the birth certificates to identify the mother and children born to the mother (siblings). We then searched for death certificates for both the FASD cases and their siblings. We then calculated the annual and age-adjusted mortality rates for the siblings of the Registry cases and compared them with mortality rates from North Dakota. RESULTS: The FASD case mortality rate was 2.4%, with a 4.5% mortality rate for their sibings, accounting for 14% of all deaths when compared to the North Dakota residents matched by age and year of death. The sibling deaths accounted for 21.5% of all cause mortality matched by age and year of death. The age-standardized mortality ratios were 4.9 for the FASD cases and 2.6 for their siblings whose FASD status was unknown. CONCLUSIONS: Mortality rates for FASD cases and their siblings were increased and represent a substantial proportion of all cause mortality in North Dakota. Prevention of FASD may be a useful strategy to decrease mortality.

Challenges of diagnosis in fetal alcohol syndrome and fetal alcohol spectrum disorder in the adult.

Adults with fetal alcohol syndrome (FAS) and the subsets of individuals with attenuated phenotype subsumed under the umbrella term of fetal alcohol spectrum disorder (FASD) provide clinicians with a challenge. Compounding this, FASD is different from most genetic syndromes since a specific diagnostic biological test is not available. The diagnosis first needs to be suspected and confirmation requires a diagnostic assessment that is best carried out in the context of a multi-disciplinary team approach. There is surprisingly little research published on the prevalence, natural history, medical, and social complications relevant to adults with FASD. The evidence that is emerging suggests that this disorder is common, and that services to diagnose and treat these individuals are limited. Adults with FASD have a higher incidence of impairments in social adaptive and executive function, and a higher degree of psychopathology when compared to the general population. The impact of FASD has significant and serious effects on those affected with FASD, their families, and our communities. There is a need for improved access to diagnosis, and more research and evaluation of interventions currently in use. In this paper, we describe the current diagnostic criteria, the differential diagnosis, the prevalence, natural history, the behavioral and mental health consequences, medical and social management issues, and interventions for adults affected with this disorder.

Increased sibling mortality in children with fetal alcohol syndrome.

We compared the rate of all-cause mortality in siblings of children diagnosed with fetal alcohol syndrome (FAS) with the siblings of matched controls. The siblings of children with FAS had increased mortality (11.4%) compared with matched controls (2.0%), a 530% increase in mortality. The age of death in case siblings deaths occurred later (between 1 day and 7 years) compared with the controls (1 day to 4 years) [odds ratio (OR)=2.4 (0.4-15.6)]. Siblings of children with FAS had increased risk of death due to infectious illness [OR=13.7 (1.2-361)] and sudden infant death syndrome compared with controls [OR=10.2 (1.2-75.1)]. A diagnosis of FAS is an important risk marker for mortality in the siblings of the proband even if they do not have FAS. Maternal alcoholism appears to be a useful risk marker for increased mortality risk in diagnosed cases and their siblings. This has important implications in the management of family members of children with FAS.

Fetal, infant, and child mortality in a context of alcohol use.

Alcohol is an important element in the causal chain of risk for fetal, infant, and childhood mortality. Mortality risk is influenced by interactions of alcohol with other environmental and genetic factors and temporal periods of susceptibility. In this paper we discuss four time periods (preconceptual, gestational, infancy, and childhood) where alcohol use may create a context of risk. Alcohol use in one period increases the risk of alcohol use in subsequent periods. Gestational alcohol use can influence risk of mortality from abuse of mother/fetus, can cause other adverse outcomes, and can result in fetal alcohol spectrum disorders (FASDs). In infancy alcohol use can increase risk from impairment of arousal in adults who use alcohol. Infants with gestational exposure can be behaviorally difficult with sleep disturbance, irritability, and colic. This can increase the risk of harm or death, especially during periods of caretakers' alcohol use. Caretakers' alcohol use and smoking are strongly correlated. The all-cause mortality rate in people diagnosed with fetal alcohol syndrome (FAS) is over 5%. All-cause mortality in siblings of diagnosed cases of FAS is increased 530% compared to siblings of matched controls. We recommend that a context of alcohol use be considered as a marker for multifactorial risk in all fetal, infant, and child deaths. A schema to collect data on alcohol use is provided to increase awareness of alcohol use as an environmental risk marker for mortality.

[The public health political status of alcohol drinking in West Germany]. / Zum gesundheitspolitischen Stellenwert des Alkoholkonsums in der Bundesrepublik Deutschland.

During the last years the per-capita-consumption of pure alcohol in the Federal Republic of Germany is slightly decreasing. In 1986 every person consumed an average of 11.5 litres of pure alcohol (146.4 litres of beer, 23.3 litres of wine and 6.1 litres of spirits). The amount of the alcohol addicts must be estimated at about 1.5 to 1.8 million people. Among the alcohol-abusers and alcohol-addicts the rate of mortality, caused by accidents, physical diseases and suicides is many times higher than among the non-drinking or rarely drinking population. Alcoholism liver-cirrhosis and pancreatitis are responsible for about 20.000 deaths per annum and for the loss of 400.000 years of life.

Blood alcohol concentration and microencephaly: a dose-response study in the neonatal rat.

The relationships among microencephaly, peak blood alcohol concentration (BAC), and dose of alcohol were examined in a rat model of third-trimester fetal alcohol effects. Ethyl alcohol was administered to neonatal rats from postnatal day 4 to day 10 during the brain growth spurt via an artificial rearing technique. Groups of rats received one of nine doses of alcohol (0.0, 2.5, 3.3, 4.0, 4.5, 5.3, 6.6, 7.5, or 8.5 g/kg body weight) administered in 8 hours each day. BACs were determined on postnatal days 6 and 7 at times corresponding to peak and trough BACs, respectively. On postnatal day 10, brains were removed, and total brain weights, cerebellar weights and brainstem weights were measured. Pups receiving 4.0 g/kg/day or less had mean peak BACs below 150 mg/dl and did not exhibit significant microencephaly when compared with controls. Higher dosages further increased the peak BAC and produced significant microencephaly. While a dose of 4.5 g/kg/day was sufficient to decrease significantly both total brain weight and cerebellar weight, a minimum dose of 6.6 g/kg/day was required for significant restriction of brainstem weight. The dose of 7.5 g/kg/day yielded a mean peak BAC of 420 mg/dl and reduced total brain weight, cerebellar weight, and brainstem weight by 33%, 52%, and 22%, respectively, relative to controls. Exposure to 8.5 g/kg/day was uniformly lethal. Peak BAC and total brain weight were highly correlated (r = -.916). As peak BAC increased, total brain weight decreased linearly. Comparisons with previous studies indicate that condensing the daily dose of alcohol effectively reduced the threshold doses for microencephaly and lethality.

Effects of prenatal ethanol exposure on physical growth, sensory reflex maturation and brain development in the rat.

In the offspring of ethanol-treated rats during gestation (25% ethanol in drinking water) decreased litter size, increased postnatal mortality rate, reduced body weight and body size, delayed ear opening, eyelid opening and teeth eruption, retarded air righting reflex acquisition, impaired brain growth, reduced cortical thickness and delayed maturation of layer Vth's pyramidal neurons: reduced basilar dendritic arborization and decreased number of spines in the apical dendrite, were observed when compared with age-matched controls fed with a standard diet. Minimal effects were found in the offspring of fibre-treated rats during gestation (standard diet mixed with cellulose) in which the body weight was similar to that of controls, although both the calorific intake from food and the mother's weight gain during pregnancy were similar to those of the ethanol-treated group. All these abnormal parameters became normal at the end of the first month of postnatal life, indicating recovery of these developmental defects produced by prenatal ethanol consumption.

A rat model of the fetal alcohol syndrome--preliminary histological findings.

A semipurified liquid diet was used to develop a chronic rat model of fetal alcohol syndrome. Adult female rats were fed a control or 40% ethanol (percent of total caloric intake) liquid diet. Additional controls were pair fed to the 40% experimental group. Results of the effects of these diets on the offspring included both qualitative and quantitative changes observed in Golgi study of hippocampal pyramidal neurons.

A rat model (using a semipurified diet) of the fetal alcohol syndrome.

A semipurified liquid diet was used to develop a chronic rat model of the fetal alcohol syndrome. Control female rats gained weight normally, reproduced normally, and gave birth to normal litters on this diet. Increased neonatal mortality, decreased neonatal weights, and altered sex ratios were observed in offspring of experimental alcoholic animals. Preliminary histological results include a mild delay in cell lamination patterns in the cerebral cortex at 4 days postnatal in alcoholic offspring as well as decreased formation of dendritic spines at 7 days postnatal.