BACKGROUND: In this prospective cohort study, we investigated the association between fatty acid ethyl esters (FAEEs) in meconium as biomarkers of prenatal ethanol exposure and growth deficits, as birth outcomes, that constitute several of the key cardinal features of fetal alcohol syndrome. METHODS: A total of 157 meconium samples were collected from enrolled infants within 24 hours of birth, and nine FAEEs were quantified using liquid chromatography/tandem mass spectrometry. The relationships between cumulative concentrations of nine species of FAEEs in meconium and birth parameters of growth (age-sex-specific centiles of head circumference [HC], weight, and length) and respective and combined birth outcomes of growth deficits (HC ≤ 10th centile, weight ≤ 10th centile, and length ≤ 10th centile) were determined. RESULTS: Multivariate logistic regression analysis demonstrated that higher cumulative concentrations of meconium FAEEs correlated with elevated risks for HC and length, both, 10th percentile or less (adjusted odds ratio [aOR], 2.94; 95% confidence interval [CI], 1.12–7.74; P = 0.029) and HC and weight and length, all of them, 10th percentile or less (aOR, 3.27; 95% CI, 1.12–9.59; P = 0.031). CONCLUSION: The elevated cumulative FAEEs in meconium were associated with combined growth deficits at birth, specifically HC and length, both, 10th percentile or less, which might be correlated with detrimental alcohol effects on fetal brain and bone development, suggesting a plausible alcohol-specific pattern of intrauterine growth restriction.
Biomarkers ; Bone Development ; Brain ; Cohort Studies* ; Esters* ; Ethanol ; Fetal Alcohol Spectrum Disorders ; Head ; Humans ; Infant ; Infant, Newborn* ; Logistic Models ; Mass Spectrometry ; Meconium* ; Odds Ratio ; Parturition* ; Prospective Studies*

Cri du Chat syndrome (CdCS) is a chromosomal disease resulting from a deletion on the short arm of chromosome 5. Characteristic features include high pitched cat-like cry, distinguishing facial features, and mental retardation. Some cases have been reported in the Korean literature, but no case reports about the concrete aspects of developmental delay in CdCS patients have been published. Therefore, we report a CdCS patient with developmental delay who was misdiagnosed as fetal alcohol syndrome. The result of the Korean-Child Development Review and Sequenced Language Scale for Infants showed severe developmental retardation, especially in expressive language.
Arm ; Centers for Disease Control and Prevention (U.S.) ; Chenodeoxycholic Acid ; Chromosomes, Human, Pair 5 ; Cri-du-Chat Syndrome ; Fetal Alcohol Syndrome ; Humans ; Infant ; Intellectual Disability

Fetal alcohol syndrome (FAS) is a developmental neuropathology resulting from in utero exposure to ethanol; many of ethanol's effects are likely to be mediated by the neurotransmitter gamma-aminobutyric acid (GABA). We studied modulation of the neurotransmitter receptor GABABR and its capacity for intracellular signal transduction under conditions of ethanol treatment (ET) and RNA interference to investigate a potential role for GABA signaling in FAS. ET increased GABAB1R protein levels, but decreased protein kinase A-alpha (PKA-alpha), calcium/calmodulin-dependent protein kinase II (CaMKII) and phosphorylation of cAMP-response element binding protein (p-CREB), in cultured hippocampal neurons harvested at gestation day 17.5. To elucidate GABAB1R response to ethanol, we observed the effects of a GABABR agonist and antagonist in pharmacotherapy for ethanol abuse. Baclofen increased GABABR, CaMKII and p-CREB levels, whereas phaclofen decreased GABABR, CaMKII and p-CREB levels except PKA-alpha. Furthermore, when GABAB1R was knocked down by siRNA treatment, CaMKII and p-CREB levels were reduced upon ET. We speculate that stimulation of GABAB1R activity by ET can modulate CaMKII and p-CREB signaling to detrimental effect on fetal brain development.
Animals ; Baclofen ; Brain ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; Carrier Proteins ; Ethanol ; Fetal Alcohol Syndrome ; gamma-Aminobutyric Acid ; Hippocampus ; Neurons ; Neurotransmitter Agents ; Phosphorylation ; Pregnancy ; Protein Kinases ; Rats ; Receptors, Neurotransmitter ; RNA Interference ; RNA, Small Interfering ; Signal Transduction

The prenatal ethanol exposure induced the alterations of dendritic spine and synapse in visual cortex and their long-term effect would be investigated in mice from P0 to P30. Pregnant mice were intubated ethanol daily from E5 through the pup's birth to establish mode of prenatal alcohol abuse. The dendritic spines of pyramidal cells in visual cortex of pups were labeled with DiI diolistic assay, and the synaptic ultrastructure was observed under transmission electron microscope. Prenatal alcohol exposure was associated with a significant decrease in the number of dendritic spines of pyramidal neurons in the visual cortex and an increase in their mean length; ultrastructural changes were also observed, with decreased numbers of synaptic vesicles, narrowing of the synaptic cleft and thickening of the postsynaptic density compared to controls. Prenatal alcohol exposure is associated with long-term changes in dendritic spines and synaptic ultrastructure. The changes were dose-dependent with long term effect even at postnatal 30.
Animals ; Dendritic Spines ; ultrastructure ; Ethanol ; toxicity ; Female ; Fetal Alcohol Spectrum Disorders ; etiology ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Microscopy, Confocal ; Microscopy, Electron, Transmission ; Pregnancy ; Prenatal Exposure Delayed Effects ; pathology ; Pyramidal Cells ; ultrastructure ; Synapses ; ultrastructure ; Visual Cortex ; ultrastructure

OBJECTIVE: The number of Korean women of childbearing age who drink alcohol and binge drink has increased remarkably in recent years. In the present study, we examined self-reported rates of alcohol use before and during pregnancy and identified maternal characteristics associated with drinking in pregnancy. METHODS: One thousand pregnant Korean women who visited the Department of Obstetrics and Gynecology (OB/GYN) completed a self-administered questionnaire that sought information on their demographic characteristics and incorporated features of the Alcohol Use Disorder Identification Test (AUDIT)-C to investigate their use of alcohol, including binge drinking, during three time periods ("in the year before this pregnancy," "during this pregnancy," and "in the previous 30 days"). RESULTS: Of these participants, 16.4% reported using alcohol during their pregnancy, 12.2% had used alcohol in the previous 30 days, and 1.7% reported binge drinking during their pregnancy. In the year before pregnancy, 77.1% had used alcohol, and 22.3% had binge drunk. The group using any amount of any alcohol during pregnancy showed a lower educational level, a lower rate of planned pregnancy, a lower level of knowledge relating to the risks of drinking alcohol during pregnancy, and a higher frequency of alcohol drinking in the year before pregnancy when compared with the abstinent group. Low educational level and unplanned pregnancy were revealed to be significant risk factors for alcohol consumption in pregnant women. CONCLUSION: This is the first study to examine any alcohol and binge alcohol drinking during pregnancy in Korea. Clinical attention and monitoring system on alcohol use during pregnancy are necessary in Korea.
Alcohol Drinking ; Binge Drinking ; Drinking ; Family Planning Services ; Female ; Fetal Alcohol Syndrome ; Gynecology ; Humans ; Korea ; Obstetrics ; Pregnancy ; Pregnancy, Unplanned ; Pregnant Women ; Surveys and Questionnaires ; Risk Factors

Alcohol is a well-known cytotoxic agent which causes various kinds of neuronal damage. In spite of thousands of published studies, the true mechanism of alcohol-induced neuronal damage remains unclear. Neurogenesis is the generation of neurons from neural stem cells (NSCs) and occurs in predominantly two regions of the brain, the subventricular zone and the dentate gyrus of the hippocampus. NSCs are the self-renewing, multipotent precursor cells of neurons, astrocytes, and oligodendrocytes in the central nervous system. Recent studies have begun to illuminate the role of neurogenesis in the biological and cellular basis of psychiatric disorders and several clinical symptoms seen in alcoholism such as depression, cognitive impairment, underlying stress and brain atrophy have been linked to impaired neurogenesis. Heavy alcohol consumption decreases neurogenesis in animals, while in vitro studies have shown decreased generation of new neurons after alcohol exposure. These findings suggest that decreased neurogenesis is important in the pathophysiology of alcoholism. Neurogenesis can be divided into four stages; proliferation, migration, differentiation and survival. Our in vitro studies on NSCs showed that alcohol decreased neuronal differentiation at doses lower than those that affected cell survival and suggested that neuron-restrictive silencer factor, or repressor element-1 silencing transcription factor (NRSF/REST) could be involved in alcohol-induced inhibition of neuronal differentiation. In an animal model of fetal alcohol effects behavioral symptoms improved after NSC transplantation. Neurogenesis could be the target for new strategies to treat alcohol related disorders.
Alcohol Drinking ; Alcohol-Related Disorders ; Alcoholism ; Animals ; Astrocytes ; Atrophy ; Behavioral Symptoms ; Brain ; Cell Survival ; Central Nervous System ; Dentate Gyrus ; Depression ; Fetal Alcohol Spectrum Disorders ; Hippocampus ; Models, Animal ; Neural Stem Cells ; Neurogenesis ; Neurons* ; Oligodendroglia ; Transcription Factors

Alcohol ingestion during pregnancy can be damaging to embryonic and fetal development. A specific pattern of malformation, identified as Fetal alcohol syndrome, has been documented in 1~2 of every 1,000 live infant births Fetal alcohol syndrome is characterized by growth deficiency, facial abnormalities, cardiac defects, minor joint and limb abnormalities, as well as central nervous system dysfunction, including microcephaly, mental retardation and abnormal neurobehavioral development. However, there are few reports of fetal alcohol syndrome associated with hormonal abnormality or amenorrhea. Recently, a case of secondary amenorrhea, which developed in a 19-year-old woman with fetal alcohol syndrome, was experienced at our institute, but the exact cause of the amenorrhea was difficulty to find. Herein, this case is reported, with a review of the literature.
Amenorrhea* ; Central Nervous System ; Eating ; Embryonic and Fetal Development ; Extremities ; Female ; Fetal Alcohol Spectrum Disorders* ; Humans ; Infant ; Intellectual Disability ; Joints ; Microcephaly ; Parturition ; Pregnancy ; Young Adult

PURPOSE: Here, we report a case of an infant with fetal alcohol syndrome with esotropia who was born to a mother who consumed a large quantity of alcohol during her pregnancy. METHODS: A 1-year-old female infant visited our hospital for the main symptom of the esodeviation of the eye. The medical history of the mother and the delivery history were reviewed, and a physical examination and ophthalmic examination of the infant were performed. RESULTS: At the first examination, the patient was 15 months old, her mass was 5, 600 grams, her height was 70 cm, her head circumference was 39.5 cm, and her chest circumference was 41 cm; all the measurements were below the 3rd percentile. From the gestation age of 24 weeks, the mother consumed 1-2 bottles of sojoo every day, and the infant patient was delivered at the gestation age of 42 weeks by Cesarean section. The infant's birth weight was 1, 510 grams. Upon physical examination, her philtrum was found to be shallow, and microcephaly was detected. Upon ophthalmic examination, a refractive error +1.25 Dsph. was detected. With regard to the horizontal length of the palpebral fissure, the right and the left were 1.7 cm and 1.6 cm, respectively, which is considered short; telecanthus and esotropia were also present. CONCLUSIONS: To the best of our knowledge, this is the first reported case of fetal alcohol syndrome with accompanying esotropia.
Birth Weight ; Cesarean Section ; Esotropia* ; Female ; Fetal Alcohol Spectrum Disorders* ; Head ; Humans ; Infant ; Lip ; Microcephaly ; Mothers ; Physical Examination ; Pregnancy ; Refractive Errors ; Strabismus ; Thorax

Fetal alcohol syndrome can be suspected in infants born to mothers with a prenatal history of alcohol abuse if the child exhibits characteristic facial features, together with intrauterine growth retardation, multiple neurological abnormalities, and multiorgan defects. If only a few of the above criteria are satisfied, the term fetal alcohol effects is used. We experienced a neonate who presented with hydrocephalus, low birth weight, seizure, right renal agenesis, characteristic facial features and a maternal history of alcohol abuse, and diagnosed him as fetal alcohol syndrome(FAS), with accompanying meconium aspiration syndrome, and persistent pulmonary hypertension of the newborn. There is no definite cure for FAS, but it can be prevented by maternal abstinence from drinking; thus maternal education, understanding and early diagnosis of those affected are of importance.
Alcoholism ; Child ; Drinking ; Early Diagnosis ; Education ; Fetal Alcohol Spectrum Disorders* ; Fetal Growth Retardation ; Humans ; Hydrocephalus ; Hypertension, Pulmonary* ; Infant ; Infant, Low Birth Weight ; Infant, Newborn* ; Meconium Aspiration Syndrome ; Mothers ; Seizures

The teratogenic effects of alcohol have been recognized in fetal alcohol syndrome (FAS). FAS is a collection of signs and symptoms seen in some children exposed to alcohol in the prenatal period. An 8 month-old-male with an alcoholic mother was diagnosed as a case of FAS according to the following : 1) early-onset intrauterine growth retardation and persistent postnatal growth failure 2) psychomotor retardation 3) craniofacial dysmorphism. Early diagnosis and continued education are advantageous at all levels, benefiting both the individual and all of society. We present this case with a brief review of related literatures.
Alcoholics ; Child ; Early Diagnosis ; Education ; Fetal Alcohol Spectrum Disorders* ; Fetal Growth Retardation ; Humans ; Mothers