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PubMed2005

Alcohol consumption among low-income pregnant Latinas.

BACKGROUND: Due to changing cultural norms, Latinas of childbearing age residing in the U.S. may be at increasing risk of drinking harmful levels of alcohol during pregnancy, and may also be unaware of the risks for Fetal Alcohol Spectrum Disorders associated with this behavior. We assessed the prevalence of alcohol consumption in a sample of low-income pregnant Latinas and examined risk factors for alcohol use in the periconceptional period. METHODS: As part of a larger intervention trial, a cross-sectional in-home interview study was conducted among a sample of 100 pregnant low-income Latinas receiving services from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) in San Diego County, California. RESULTS: Fifty-seven percent of respondents indicated they were either life-time abstainers or had not consumed any alcohol in the periconceptional period. Forty-three percent reported some alcohol use in the three months prior to recognition of the current pregnancy, and 20% reported at least one binge episode of four or more standard drinks during that time frame. Five percent reported drinking seven or more drinks per week, and 8% continued drinking alcohol after recognition of pregnancy. Significant predictors of any alcohol use in the periconceptional period included English language/higher level of acculturation, younger maternal age, lower parity, higher level of education, younger age at first drink, and having ever smoked. Women who were aware of alcohol warning messages and /or had more knowledge of the Fetal Alcohol Syndrome (FAS) were significantly more likely to have consumed alcohol in the periconceptional period. Frequency of periconceptional use of alcohol did not differ between women who planned or did not plan the pregnancy. CONCLUSION: The prevalence and pattern of early pregnancy alcohol consumption in this sample of Latinas is similar to patterns noted in other race/ethnic groups in the U.S. Level of knowledge about FAS and awareness of warning messages was not protective for early pregnancy alcohol consumption, suggesting that specific knowledge was insufficient to prevent exposure or that other factors reinforce maintenance of alcohol consumption in early pregnancy. Selective interventions in low-income Latinas are warranted, and should be focused on women of reproductive age who are binge or frequent drinkers and who are at risk of becoming pregnant.

Acculturation↗
PubMed2006

A staged screening strategy for prenatal alcohol exposure and maternal risk stratification.

AIMS: To present an incremental process for a staged screening strategy to identify women at increased risk of having a child with fetal alcohol spectrum disorder (FASD) and to enhance the management of women using alcohol during pregnancy. We include an illustrative example of the development of a screening component using an existing data set. METHODS: We describe a seven-step protocol to screen for alcohol use during pregnancy. The screening process begins with a one-question initial screen, followed by exposure assessment, maternal risk stratification to estimate risk for FASD, and concludes with recommendations for intervention and monitoring of exposure for women drinking during pregnancy. CONCLUSIONS: This screening process has very modest time commitments in the early stages. Time commitments increase for women drinking during pregnancy and the process focuses on the population at highest risk of having a child with FASD. The process has the benefit of risk specificity, since the process refines risk estimates for an adverse outcome specific for FASD. The process concludes with a programme to facilitate intervention and to monitor changes in prenatal alcohol exposure during pregnancy. Prevention of FASD is an important public health priority. In addition to the ongoing study of clinical strategies to improve detection rates of alcohol exposure at all stages of pregnancy, additional research on the tools and the process used in screening efforts is urgently needed. The efforts should also include research on both the screening tools and the outcome of the screening process in routine prenatal care settings.

Alcohol Drinking↗
PubMed2004

Implicit strategy affects learning in children with heavy prenatal alcohol exposure.

BACKGROUND: Learning and memory deficits are commonly reported in children with heavy prenatal alcohol exposure. Our recent work suggested that children with heavy prenatal alcohol exposure retained information as well as controls on a verbal learning test but not on a test of nonverbal learning and memory. To better understand the cause of this differential pattern of performance, the current study re-analyzed data from our previous study to determine if the presence of an implicit learning strategy may account, at least in part, for the finding of spared retention. METHODS: The current study examined verbal learning and memory abilities in 35 children with Fetal Alcohol Spectrum Disorders (FASD) and 34 nonexposed controls (CON) matched for age (9-16 years), sex, ethnicity, handedness, and socioeconomic status. Groups were compared on two measures of verbal learning, one with an implicit strategy (California Verbal Learning Test-Children's Version; CVLT-C) and one without (Verbal Learning subtest of the Wide Range Assessment of Memory and Learning; VL-WRAML). RESULTS: Children with FASD learned less information overall than children in the CON group. Both groups learned a greater percentage of information and reached a learning plateau earlier on the CVLT-C compared with the VL-WRAML. Groups also showed comparable rates of retention after a delay on the CVLT-C. In contrast, on the VL-WRAML, children with FASD showed poorer retention rates than children in the CON group. Interestingly, children with FASD did not differ from children in the CON group on CVLT-C semantic clustering scores for learning trials 1 through 3, and greater utilization of semantic clustering was correlated with better learning and memory performance in both groups. This overall pattern of results was not related to overall intellectual level. CONCLUSIONS: The finding of spared retention of verbal information on the CVLT-C in our earlier studies may be related to test characteristics of the CVLT-C rather than a finding of spared verbal retention per se, given that spared retention was not found on a separate test of verbal learning and memory without an implicit learning strategy. These results suggest that the use of an implicit strategy positively affected the ability of alcohol-exposed children to learn and retain new verbal information.

Adolescent↗
PubMed2026

Prenatal Alcohol Exposure Produces Selective Changes in Neuroimmune Gene Expression Across Brain Regions of Adult Mice.

BACKGROUND: An overwhelming body of evidence suggests neuroimmune dysfunction as a key underlying mechanism of fetal alcohol spectrum disorder (FASD)-associated adverse central nervous system (CNS) outcomes. While few studies have highlighted the lingering effects of prenatal alcohol exposure (PAE) on producing specific immune factors, others suggest a primed neuroimmune state in adulthood, in which a proinflammatory bias is unmasked following subsequent immune activation in later life. However, the PAE-induced neuroimmune landscape in adulthood remains poorly defined. We hypothesized that PAE induces long-term changes in gene expression linked to neuroimmune function that may be brain region-specific. METHODS: Using long-read next-generation RNA sequencing of brain tissues from a previously established model of a moderate PAE in mice, we compared across six regions: medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), hypothalamus, hippocampus, midbrain, and medulla. A comprehensive bioinformatics analysis investigated PAE-induced changes, dysregulated gene pathways, and transcriptional regulators with a focus on neuroimmune function. RESULTS: Our data identified at least 60 differentially expressed genes per brain region, many of which were associated with neuroimmune function. Upregulation of multiple pro-inflammatory factors and pathways was observed, suggesting ongoing baseline neuroimmune activation, potentially involving PXR, TNF, TLR4, the complement pathway, and various cytokine and chemokine signaling. A comparative analysis identified multiple upstream transcriptional regulators across multiple brain regions, including MECP2, TCF7L2, and IL-4. Importantly, this unbiased analysis revealed heterogeneity across brain regions in the activation of canonical immune pathways and highlighted previously unprecedented roles of pathways such as PXR, matrix metalloproteases, and cytokine signaling (e.g., IL-15, IL-27, IL-17) in PAE. CONCLUSIONS: PAE creates a unique inflammatory signature in the adult brain, even in the absence of secondary injury, with novel patterns of region-specific changes in genes implicated in glial-immune function. These data identify potential immune targets to elucidate the mechanisms underlying behavioral dysfunction and provide a framework for future therapeutic interventions.

Animals↗
PubMed2006

Epidemiology of FASD in a province in Italy: Prevalence and characteristics of children in a random sample of schools.

BACKGROUND: Accurate estimates of the prevalence and characteristics of fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorders (FASD) in a Western European population are lacking and are of particular interest in settings where the usual pattern of alcohol consumption is thought to be daily drinking with meals. To address these issues, an epidemiology study of FAS and other FASD was undertaken in Italian schools. METHODS: Primary schools (n = 25) in 2 health districts of the Lazio region were randomly selected and recruited for the study. Five hundred forty-three children, 50% of those enrolled in first-grade classes, received parental permission to participate in a 2-tiered, active case ascertainment screening process. Detailed evaluation of children selected in a preliminary screening phase was carried out on those who were small for height, weight, and head circumference and/or referred by teachers for suspected learning and behavioral problems. Detailed evaluation was carried out on each child's: (1) physical growth and dysmorphology, (2) psychological development and behavior, and (3) prenatal exposure to alcohol and other risk factors for FASD via maternal interviews. A group of 67 randomly selected children without FASD from the same classes was utilized as a comparison group. RESULTS: Using 2 denominators for prevalence estimation, a conservative one and a strict sample-based estimate, the prevalence of FAS in this province of Italy was 3.7 to 7.4 per 1,000 children. When cases of partial FAS (PFAS) and a case of alcohol-related neurodevelopmental deficits (ARND) were added to FAS cases, the rate of FASD was 20.3 to 40.5 per 1,000 and estimated at 35 per 1,000 overall or between 2.3 and 4.1% of all children. This exceeds previously published estimates of both FAS and FASD for the western world. Detailed data are presented that demonstrate the utility of the guidelines of the revised Institute of Medicine diagnostic criteria for FASD. Children with FASD are significantly more impaired/affected (p < 0.05) than randomly selected comparison children on all measures of growth deficiency, key facial features of FASD, overall dysmorphology scores, language comprehension, nonverbal IQ, and behavior. Maternal reports of current drinking were significantly higher for mothers of FASD children than comparison mothers, but reported rates of overall drinking during pregnancy were not significantly different. In contrast to expectations, daily drinking among mothers of the comparison group was not common. However, dysmorphology scores of the children were significantly correlated with drinking in the second and third trimesters, drinks per current drinking day, and current drinks per month. Finally, children with the physical features of FASD had lower IQs; nonverbal IQ was significantly correlated with head circumference and negatively correlated with overall dysmorphology score, smooth philtrum, and several other facial and physical anomalies characteristic of FAS. CONCLUSIONS: Using careful measures of ascertainment in a primary school setting, these results provide relatively high estimates of the prevalence of FASD and raise the question of whether FASD is more common in the western world than previously estimated.

Abnormalities, Drug-Induced↗
PubMed1984

Prenatal effects of alcohol.

Suspicion of alcohol's teratogenic potential stretches back many centuries, but it is only recently that solid support for this possibility has been produced. There is now little doubt that alcohol can produce developmental defects, but there are many questions that still remain to be answered concerning the impact of alcohol on the conceptus. One major question that remains to be resolved is why only a small percentage of alcoholic women give birth to children with Fetal Alcohol Syndrome (FAS), whereas other alcoholic women who drink the same amount do not. Another important issue concerns the way in which alcohol produces its effects. Although one of the most likely ways in which alcohol's teratogenic actions are mediated appears to be via hypoxia, other mechanisms such as direct toxicity of alcohol or acetaldehyde may be involved. FAS refers to a pattern of defects in children born to alcoholic women. For a diagnosis of FAS to be made, the patient must have three main characteristics: (1) pre- and postnatal growth retardation (greater than or equal to 2 S.D. for length and weight), (2) facial anomalies, and (3) central nervous system dysfunction Pre- and postnatal growth retardation are the most reliable consequences of fetal alcohol exposure. In many cases, patients with the syndrome weigh less than 2500 g at birth and most do not exhibit postnatal 'catch-up growth' Among the distinctive facial anomalies seen in conjunction with the syndrome are absent-to-indistinct philtrum, epicanthic folds, thin upper lip and short upturned nose. Joint, limb and cardiac anomalies are also often present. Central nervous system dysfunction includes mental retardation, the most serious consequence of in utero alcohol exposure, hyperactivity, sleep disorders and miscellaneous behavioral difficulties. If only one or two of these broad characteristics are present and the mother is suspected of drinking during pregnancy, then a diagnosis of 'possible fetal alcohol syndrome,' or 'partial fetal alcohol syndrome,' or 'fetal alcohol effects,' or 'alcohol-related birth defects' may be made. However, without evidence of maternal drinking during pregnancy, this diagnosis is very tentative, since many of these effects are also observed in conjunction with many other congenital disorders.(ABSTRACT TRUNCATED AT 400 WORDS)

Abortion, Spontaneous↗
PubMed1997

Arthrogryposis multiplex congenita and bilateral mid-brain infarction following maternal overdose of co-proxamol.

We report a case of arthrogryposis multiplex congenita secondary to fetal hypokinesia in a 41-week gestation infant following antenatal central nervous system injury. The mother's pregnancy was complicated by an episode of attempted self harm, with an overdose of co-proxamol at 22 weeks of gestational age, and by the use of cocaine in combination with excess alcohol intake. Magnetic resonance imaging showed bilateral mid-brain cysts and marked atrophy of the basal ganglia and thalami.

Acetaminophen↗
PubMed2004

Prenatal ethanol exposure alters the postnatal development of the spontaneous electrical activity of dopamine neurons in the ventral tegmental area.

Prenatal ethanol exposure causes a persistent reduction in the spontaneous electrical activity of dopamine (DA) neurons in the ventral tegmental area (VTA) in adult animals. Because DA neuron activity matures into adult pattern during postnatal development, it is possible that reduced activity in VTA DA neurons after prenatal ethanol exposure is caused by impaired postnatal development. This possibility was investigated in the present study using the in vivo extracellular single-unit recording and brain stimulation techniques. The results show an age-dependent decrease in the number of spontaneously active VTA DA neurons from 2 to 4 weeks of age in both the control and prenatal ethanol-exposed animals. In ethanol-exposed animals, the age-dependent decrease was more prominent after 3 weeks of age, resulting in lower numbers of spontaneously active VTA DA neurons in 4-week-old and adult animals. In both the control and ethanol-exposed animals, there were age-dependent increases in the firing rates and burst firing activity of VTA DA neurons after 2 weeks of age. Ethanol exposure led to slightly lower firing rates in 4-week-old and adult animals and did not impact the burst firing pattern in any age groups. There were no changes in axon conduction velocity and antidromic spike characteristics of VTA DA neurons. These results indicate that reduced activity of VTA DA neurons during adulthood after prenatal ethanol exposure does not begin prenatally. Instead, it is a result of impaired postnatal development manifested only when animals reach 4 weeks of age. These results suggest that early intervention may be an effective treatment strategy for attention deficit/hyperactivity disorder, a behavioral dysfunction related to the abnormalities of DA systems and often observed in children with fetal alcohol spectrum disorder.

Action Potentials↗
PubMed2026

Cloning of human DING: Developmental expression and downregulation by EtOH in-utero.

INTRODUCTION: An estimated 15-20% of women consume alcohol (EtOH) during pregnancy. Women with alcohol use in early pregnancy are likely to have a child with fetal alcohol spectrum disorders (FASD). Recently, we reported neuroprotective effects of human DING (a member of the DING family of phosphatases) against EtOH-mediated toxicity in rats and in human fetal cortical neurons in vitro. Now, we report the sequencing and developmental expression patterns of endogenous DING in human fetal brain. METHODS: DING cDNA was cloned from human U87MG astrocytoma cells with primers specific to the plant DING gene and known prokaryotic DING genes. This cDNA was used to prepare antibodies. The full-length human DING gene p38hu (1095 nucleotide bases) is flanked by the first initiating codon, ATG, and the last, stop codon, TAA. Post-mortem fetal tissues and maternal blood were collected during pregnancy between 8 and 37 weeks' gestation. The developmental, spatial, and temporal expression of DING protein in fetal brain tissue was analyzed by immunohistochemistry. Developmental expression of DING in fetal brain and placenta was quantified by qWestern blots. DING promoter expression was assayed by ddPCR. Statistical analysis included ANOVA. RESULTS: Sequencing revealed different-sized genomic DNA clones. The anti-DING antibody detected proteins ranging in size from 35 to 40 kDa, and high molecular weight precursor protein in fetal brain and placenta. DING protein was present in fetal brain at early stages and its level was increased at later gestational ages. The DING promoter was expressed in fetal brain, neurospheres, and fetal brain-derived exosomes. DING levels were reduced in samples exposed to maternally consumed alcohol. CONCLUSIONS: Because DING is neuroprotective, its reduced expression in fetuses exposed to alcohol may suggest a mechanism that contributes to the pathogenesis of FASD, which could lead to the development of therapeutic tools aimed at preventing, ameliorating or reversing this prevalent group of syndromes that are implicated in as many as 5% of births world-wide.

DING gene cloning↗
PubMed2006

Binge drinking during pregnancy as a predictor of psychiatric disorders on the Structured Clinical Interview for DSM-IV in young adult offspring.

OBJECTIVE: This study explored the extent to which the high frequency of psychiatric problems reported in clinical groups with fetal alcohol spectrum disorders might also be observed in a nonclinical group of young adults and the psychiatric conditions that are related to prenatal alcohol exposure in this group. METHOD: From a longitudinal prospective study beginning with interviews of 1,529 pregnant women, a birth cohort of about 500 newborns was chosen to include all of the most heavily alcohol exposed plus a sampling of the continuum of alcohol exposures from total abstinence through heavy drinking. At an average age of 25.7 years, 400 members of this birth cohort were administered valid Structured Clinical Interviews for DSM-IV (SCID), including both the SCID for axis I disorders and the SCID for axis II personality disorders. RESULTS: The odds of the appearance of six psychiatric disorders and traits were more than double in adults exposed to one or more binge alcohol episodes in utero. Three of these six odds ratios were uniformly stable against confounding: axis I substance dependence or abuse disorders and axis II passive-aggressive and antisocial personality disorders or traits. CONCLUSIONS: Prenatal exposure to alcohol may be a risk factor for specific psychiatric disorders and traits in early adulthood, even in a nonclinical group.

Adolescent↗
PubMed2006

Binge alcohol exposure during all three trimesters alters bone strength and growth in fetal sheep.

Women who drink while pregnant are at a high risk of giving birth to children with neurodevelopmental disorders. Heavy consumption of alcohol during pregnancy is also known to be deleterious to fetal bone growth in both humans and laboratory animals. However, nothing is known regarding the effect of maternal moderate and heavy alcohol binging on fetal and maternal bone strength. The purpose of this study was to determine the effects of moderate and heavy alcohol binging throughout gestation on fetal and maternal bone growth and strength. The study was conducted using an ovine model system. The large body mass of the ovine fetus, the longer gestation that is more similar to that of humans, and the fact that all three trimester equivalents occur in utero, make the sheep an excellent model for studying Fetal Alcohol Spectrum Disorder. Suffolk ewes were mated and, beginning on gestational day 4, received intravenous infusions over 1 h on 3 consecutive days per week followed by 4 days without treatment concluding on day 132 of pregnancy. Pregnant ewes were divided into four groups: two alcohol treatment groups (0.75 and 1.75 g/kg of body weight), one pair-fed saline control group, and an untreated normal control group. The fetuses were harvested on gestational day 133. Maternal and fetal femoral and tibial dimensions were measured and the maximum strength (MPa) carried by the bone tissue was determined using a three-point bending procedure. Maternal bones were not different among groups. The higher alcohol dose resulted in reduced fetal femoral bone strength, whereas the tibial bone strength was lower when compared with the normal control subjects. In contrast, the lower alcohol dose increased fetal femoral strength compared to the normal control subjects. The alcohol-exposed fetal bones also tended to exhibit reduced lengths. We conclude that binge alcohol exposure throughout gestation resulted in dose-dependent differences in the maximum stress absorbed by the fetal bones.

Alcohol Drinking↗
PubMed2006

Drugs of abuse testing in meconium.

Prenatal substance abuse is an ongoing concern with significant impact on neonatal health and development across socioeconomic lines. Meconium, passed by neonates during their first post-natal bowel movements, is a matrix unique to the developing fetus and contains a long history of prenatal metabolism. Over the last two decades, the use of meconium as a matrix for assessing prenatal exposure to drugs of abuse has yielded methods exhibiting higher sensitivity, easier collection, and a larger window of detection than traditional matrices. Recently, a method has been developed for the analysis of fatty acid ethyl esters in meconium as a biomarker of fetal alcohol exposure, potentially facilitating the future diagnosis of Fetal Alcohol Spectrum Disorder in situations where gestational alcohol consumption history is unknown. Screening for prenatal exposure to illicit and abused licit drugs in meconium is possible by use of a variety of immunoassay methods with conformational analysis usually occurring by GCMS or LCMS. In spite of increased sample preparation time relative to blood and urine, the long metabolic history, coupled with the ease and wide window of collection of meconium make it the ideal matrix for determining fetal drug exposure.

Female↗
PubMed1996

Fetal gammaglutamyl transferase activity: clinical implication in fetal medicine.

In a retrospective study of 3,129 fetal blood samples, we first determined normal values for gammaglutamyl transferase (GGT) activity and found 33 cases with a mean GGT level of 961.8 U/l (prevalence 1.05%) corresponding to more than 10-fold normal values. In such extreme cases, elevations of GGT activity in fetal blood have been poorly studied. The goal of this work was to correlate this highly abnormal biological finding with pathological fetal conditions and try to better understand the pathophysiological mechanisms. The most frequent underlying disorders were infections (n = 11), renal or bowel malformations (n = 12) and genetic abnormalities (n = 5). Two cases of cystic fibrosis and one case of fetal alcohol syndrome were also encountered. In another 2 cases, no explanation was found.

Chromosome Aberrations↗