Historical misrepresentation in science: The case of fetal alcohol syndrome

The history of the fetal alcohol syndrome (FAS) provides a microcosm in which to explore the larger ramifications of historical citations in biomedical publications. Though some historical references such as Biblical writings may hint at a rudimentary understanding of the relationship between maternal drinking and fetal development, no definitive case can be made for an understanding of FAS dating back hundreds of years. Authors who claim an impressive history for FAS misrepresent that history. The modern history of FAS raises a question concerning citations of original discoveries. The first paper describing ethanol-induced damage to the fetus appeared in 1968 yet most researchers cite one of two papers from 1973. Both ancient citations and modern references to original discoveries pose difficult questions for the scientist. Both dilemmas may be solved by a better reading of the literature and a more judicious wording when writing about history. This work was supported in part by Grant # AA10681 to SNP.     

Fetal Alcohol Spectrum Disorders: An Overview

When fetal alcohol syndrome (FAS) was initially described, diagnosis was based upon physical parameters including facial anomalies and growth retardation, with evidence of developmental delay or mental deficiency. Forty years of research has shown that FAS lies towards the extreme end of what are now termed fetal alcohol spectrum disorders (FASD). The most profound effects of prenatal alcohol exposure are on the developing brain and the cognitive and behavioral effects that ensue. Alcohol exposure affects brain development via numerous pathways at all stages from neurogenesis to myelination. For example, the same processes that give rise to the facial characteristics of FAS also cause abnormal brain development. Behaviors as diverse as executive functioning to motor control are affected. This special issue of Neuropsychology Review addresses these changes in brain and behavior highlighting the relationship between the two. A diagnostic goal is to recognize FAS as a disorder of brain rather than one of physical characteristics.     

Infant irritability: The impact of fetal alcohol exposure,maternal depressive symptoms,and low emotional support from the husband

Objectives: The aim of this study was to investigate the impact of fetal alcohol exposure, maternal depressive symptoms, and low emotional support from the husband on infant irritability in the first one and a half years of life. Four models describing the interplay of these factors were assessed: A direct effect model, an interaction or threshold model, a mediational model and a transactional model. Method: A sample of initially 458 women was assessed in a prospective 3‐wave study across the first 17 months after childbirth. Fetal alcohol exposure was questioned retrospectively six weeks after birth. Infant irritability was reported by the mothers and fathers. Results: Support for the direct effect model and the interaction model could be found: Fetal alcohol exposure and low emotional support from the husband were associated with increased infant irritability at 5 months. The impact of fetal alcohol exposure was moderated by postnatal depressive symptoms. More irritability was reported if both risk factors, prenatal alcohol exposure and maternal depressive symptoms, were present. Infant irritability and maternal depressive symptoms were associated cross‐sectionally. At the age of 17 months only a main effect of prenatal alcohol exposure on irritability could be found. Conclusion: Direct effects of fetal alcohol exposure, maternal depressive symptoms, and low emotional support from the husband on infant irritability as well as an interaction between fetal alcohol exposure and maternal depressive symptoms were revealed. The interaction can be understood in terms of a diathesis‐stress model. However, no longitudinal associations between maternal depressive symptoms and infant irritability could be found.     

Prenatal diagnosis and management of intrauterine growth restriction: A long‐term prospective study on outcome and maternal stress

This study examines long‐term effects of antenatal management of intrauterine growth restriction (IUGR) on developmental outcome and on maternal coping using a prospective cross‐sectional design. Sixty‐nine families were evaluated using psychological testing and risk questionnaires. The effects of timing of diagnosis (prenatal/perinatal) and of pregnancy management [induction of labor (IL)/conservative management (CM)/none, i.e., diagnosed‐at‐birth (DaB)] on maternal stress were tested at 6 years' postbirth. In general, prenatal management protocols of IUGR were efficient in preventing major disabilities; however, 49% of the variance in maternal stress at 6 years' postbirth could be attributed to the child's presenting behavior and to pregnancy management of IUGR condition. Mothers who received CM treatment reported being more stressed by their child's poor emotional adjustment (ps < .01–.002) and distractibility (p < .029), and to have more difficulty in accepting them (p < .01). Prenatal psychological consultation to better handle stress for parents whose fetus is diagnosed with IUGR is recommended, particularly when pregnancy is managed conservatively and familial–educational resources are low.     

Intergenerational effects of cocaine on maternal aggressive behavior and brain oxytocin in rat dams

Gestational cocaine treatment results in significantly increased maternal aggression towards an intruder by postpartum day six, while acute postpartum treatment dose dependently decreases maternal aggressive (MA) behavior. Both increased and decreased aggression in the cocaine-treated dams are correlated with either decreased or increased levels of oxytocin in the amygdala, respectively. The current study was an effort to determine whether the effect of gestational cocaine on maternal aggression is transient or would continue into the postpartum period; whether an intermittent cocaine treatment regimen, which incorporates gestational and postpartum intermittent cocaine treatment, would differ from chronic daily gestational treatment; and finally, whether next generation female offspring of cocaine-treated or control dams would have altered MA behavior and oxytocin system changes attributable to either prenatal drug exposure, rearing condition or both. We now report no increase in maternal aggression following chronic gestational treatment and significantly lower levels of aggression in intermittently treated dams on postpartum day eight, with no significant effects in either group on postpartum day 12. Young adult female offspring of the cocaine-treated and control dams, who reared their own natural litters and were tested on postpartum day eight for maternal aggression, had higher levels of maternal aggression towards an intruder attributable to both prenatal cocaine exposure and rearing condition. Higher aggression in cocaine-reared next generation dams was associated with lower levels of oxytocin in the amygdala. Intergenerational effects of cocaine were apparent with respect to aggression and oxytocin system changes.     

Executive functioning deficits in preschool children with Fetal Alcohol Spectrum Disorders

Executive function (EF) deficit is a hallmark of Fetal Alcohol Spectrum Disorders (FASD), but the vast majority of available evidence comes from school-age children and adolescents. Very little is known about EF during the critical developmental period prior to 6 years of age in FASD. We evaluated EF in 39 children with FASD (3.0–5.5 years) and a comparison group of 50 age-matched, nonexposed controls. Measures included the EF Scale for Early Childhood and a Delay of Gratification task. Compared to age-matched controls, preschool children with FASD had impairments on the EF Scale and showed more impulsivity on the Delay of Gratification task. To confirm the EF Scale finding, FASD group performance was compared to a separate normative dataset (N = 1,400). Those with FASD performed below normal (M = –0.57, SD = 0.92). Within the FASD group, IQ was correlated with the EF Scale (partial r = .60, p = .001) and Delay of Gratification (partial r = .58, p = .005). EF Scale performance did not differ significantly across levels of FASD severity (fetal alcohol syndrome [FAS], partial FAS, or alcohol-related neurobehavioral disorder [ARND]). However, compared to normative data, those with FAS had the largest deficits (M = –0.91 SD from the mean, SE = 0.23), followed by partial FAS (M = –0.66 SD from the mean, SE = 0.26), then ARND (M = –0.36 SD from the mean, SE = 0.20). These novel data show that EF deficits manifest well before the age of 6 years in children with FASD, that they occur across the spectrum, and that EF may be most impaired in children with more severe forms of FASD and/or lower IQs.     

Cross-cultural perspectives on coping with the risks of maternal phenylketonuria

Abstract

Maternal phenylketonuria (PKU) refers to the deleterious effects on a fetus due to high maternal phenylalanine levels. Prevention of these effects requires that women with PKU reduce their blood phenylalanine levels prior to and throughout pregnancy which means that they plan their regnancies and adhere to a phenylalanine restricted diet. According to a psycho-social model of maternal PKU, a first necessary step in preventing the effects of maternal PKU is prevention of unplanned pregnancies i.e.: using effective family planning practices. In the present study, findings are presented on seventy-five phenylketonuric women (60 from the United States and 15 from Israel) who participate in a prospective longitudinal study, to reveal the reasons why the proportion of pregnancies treated prior to conception has consistently been higher in Israel than in the United States. The two groups were interviewed and administered a battery of tests and questionnaires measuring a wide range of variables associated with family planning. Subjects in the United States were found to have more knowledge about fertility, contraception and maternal PKU. Israeli subjects held more negative attitudes towards and were less engaged in premarital sexual relationships, more frequently used oral contraceptives, had stronger motivation to have their own children, and perceived their disease to have a more negative effect on their lives. These findings suggest that the issues in maternal PKU are cultural as well as medical and psychosocial.     

Developing the Functional Assertiveness Scale: Measuring Dimensions of Objective Effectiveness and Pragmatic Politeness

The purpose of the present study was to develop a measure for functional assertiveness, the Functional Assertiveness Scale (FAS). Functional assertiveness is a new concept of assertiveness that represents a method of appropriate self‐expression. Functional assertiveness is defined as interpersonal communication that occurs when a speaker encounters interpersonal problems that should be resolved or has objectives that should be achieved, and the speaker's message is perceived as appropriate by the listener (Mitamura & Tanaka‐Matsumi, 2010, 2010c). Five studies were conducted in order to develop the FAS. In Study 1, we generated an item pool for FAS, and in Study 2 we developed the FAS prototype using this item pool. Study 3 examined the factorial validity, concurrent validity, and internal consistency of the FAS. Study 4 examined test–retest reliability of the FAS. Study 5 examined responsiveness on the FAS. The validity and reliability of the FAS and potential utility and clinical implication of the FAS are discussed.     

Parental Psychopathology and Paternal Child Neglect in Late Childhood

We aimed at determining the association of both severity of paternal and maternal substance use disorder (SUD) and psychiatric disorders with paternal child neglect severity during late childhood. The sample comprised 146 intact SUD (n=71) and non SUD (n=75) families with a 10–12 year old female or male biological offspring. The average age of fathers, mothers, and children was 44 (SD=5.9), 42 (SD=4.78), and 11 (SD=.79) years, respectively. The ethnic composition was 85% Caucasian and 15% African American. The results showed that paternal and maternal SUD and psychiatric disorders severity was correlated with paternal child neglect severity. However, paternal psychopathology failed to achieve significance in the regression analyses. Severity of maternal, especially severity of antisocial personality disorder symptoms was associated with paternal child neglect. These results are discussed within the framework of evolutionary psychology research examining paternal investment in the offspring. Implications for the necessity of identifying parental psychopathology and an integrated treatment approach are discussed.     

Neurocognitive Impairment in Early Adolescence Following Prenatal Alcohol Exposure of Varying Duration

The aims of the study were, first, to perform a comprehensive assessment of neurocognitive status in early adolescence of children exposed to alcohol prenatally; and, second, to examine whether duration of exposure continues to be predictive of outcome at this age. Twenty-seven exposed 12-14-year-olds and 39 nonexposed 13-14-year-olds underwent neuropsychological assessments (WISC-III, NEPSY subtests) of attention and executive functions, language, visuomotor functions, and memory. The group of non-exposed children was used to develop preliminary test norms for the 13-14-year-old exposed children whereas published test norms could be used for the 12-year-olds. The results demonstrated neurocognitive impairment across all types of tasks. Impairment varied in degree according to the duration of alcohol exposure. Children exposed throughout pregnancy, most of who had diagnoses of Fetal Alcohol Syndrome (FAS) or Fetal Alcohol Effects (FAE), performed well below the average range. It was concluded that the neurocognitive effects of alcohol exposure tend to be widespread and generalized. Attention and executive functions do not seem to be selectively affected. Further, the relationship between duration of prenatal alcohol exposure and neurocognitive development continues to be significant in early adolescence.     

Fetal alcohol syndrome and the developing socio-emotional brain

Fetal alcohol syndrome (FAS) is currently recognized as the most common known cause of mental retardation, affecting from 1 to 7 per 1000 live-born infants. Individuals with FAS suffer from changes in brain structure, cognitive impairments, and behavior problems. Researchers investigating neuropsychological functioning have identified deficits in learning, memory, executive functioning, hyperactivity, impulsivity, and poor communication and social skills in individuals with FAS and fetal alcohol effects (FAE). Investigators using autopsy and brain imaging methods have identified microcephaly and structural abnormalities in various regions of the brain (including the basal ganglia, corpus callosum, cerebellum, and hippocampus) that may account for the neuropsychological deficits. Results of studies using newer brain imaging and analytic techniques have indicated specific alterations (i.e., displacements in the corpus callosum, increased gray matter density in the perisylvian regions, altered gray matter asymmetry, and disproportionate reductions in the frontal lobes) in the brains of individuals prenatally exposed to alcohol, and their relations with brain function. Future research, including using animal models, could help inform our knowledge of brain-behavior relations in the context of prenatal alcohol exposure, and assist with early identification and intervention.     

Neurocognitive impairment in early adolescence following prenatal alcohol exposure of varying duration.

The aims of the study were, first, to perform a comprehensive assessment of neurocognitive status in early adolescence of children exposed to alcohol prenatally; and, second, to examine whether duration of exposure continues to be predictive of outcome at this age. Twenty-seven exposed 12-14-year-olds and 39 non-exposed 13-14-year-olds underwent neuropsychological assessments (WISC-III, NEPSY subtests) of attention and executive functions, language, visuomotor functions, and memory. The group of non-exposed children was used to develop preliminary test norms for the 13-14-year-old exposed children whereas published test norms could be used for the 12-year-olds. The results demonstrated neurocognitive impairment across all types of tasks. Impairment varied in degree according to the duration of alcohol exposure. Children exposed throughout pregnancy, most of who had diagnoses of Fetal Alcohol Syndrome (FAS) or Fetal Alcohol Effects (FAE), performed well below the average range. It was concluded that the neurocognitive effects of alcohol exposure tend to be widespread and generalized. Attention and executive functions do not seem to be selectively affected. Further, the relationship between duration of prenatal alcohol exposure and neurocognitive development continues to be significant in early adolescence.     

Neuropsychological Effects at Early School Age of Fetal Alcohol Exposure of Varying Duration

A comprehensive neuropsychological assessment was performed with forty-six 5- to 9-year-old children exposed to alcohol in utero for varying durations. The children were subdivided according to duration of maternal alcohol abuse, as follows: during trimester I (n = 16), during trimesters I and II (n = 16), and throughout pregnancy (n = 14). A control group (n = 26) consisted of unexposed children. Fetal alcohol exposure throughout pregnancy had significant, diffuse effects on the development of the children, whereas exposure only during early pregnancy did not. Observed cognitive deficits included problems in naming, receptive language, attention, and visual-motor functions. Verbal and visual memory and manual motor precision did not significantly differ between the groups.     

Maternal Trauma and Children’s Functioning: The Role of Kinship Social Support

Although research has documented the detrimental effects of maternal trauma on child behavior (Lambert, Holzer, & Hasbun, 2014), the role of extended family support in potentially mitigating the effects of intergenerational transmission of trauma is not clearly understood. With a diverse community sample of 52 trauma-exposed mothers and their children between the ages of 7 and 12, we investigated relationships between kinship social support, maternal trauma exposure severity, maternal posttraumatic stress disorder (PTSD) symptom severity, and child behavioral problems. Results showed that kinship social support was negatively related to maternal trauma exposure severity, maternal PTSD symptom severity, child internalizing behaviors, and child externalizing behaviors. Additionally, kinship social support moderated the relationship between maternal trauma exposure severity and child internalizing behaviors. These results have implications in the implementation of interventions aimed at supporting diverse families facing trauma that incorporate extended family networks.     

Comparison of Maternal Perceptions of Preterm and Fullterm Infants

We compared maternal attitudes and feelings in two groups of mother–infant dyads: 25 mothers with preterm newborns (M=30.9 weeks of gestational age) and 25 mothers with fullterm newborns (M=39.7 weeks of gestational age). Both groups were matched for infant sex, age (corrected in preterms) and birth order as well as for maternal age and education. Semi-structured interviews were used to collect data on maternal attitudes and feelings about pregnancy and the first contacts with the newborn. Mothers completed rating scales to indicate the specific behavioural problems they perceived in their infants at 6 weeks and 3 months of (corrected) age. Observations of infant responses to visual and/or auditory stimuli were made at 6 weeks and 3 months in a laboratory setting. At 3 months, each infant was administered the Bayley Scale of Mental Development. There were no differences in maternal attitudes and feelings between the two groups of mothers prior to the birth. However, significant differences appeared after birth and indicated increased anxiety in mothers of preterm infants. Significantly more 6-week-old preterm infants were perceived by their mothers as irritable and to cry more than fullterm infants. At the age of 3 months, both groups of infants differed only in terms of irritability. Differences between the two groups of mother–infant dyads, age-related changes in these differences and relationships between maternal evaluations and the laboratory-based assessments are discussed in the context of contrasts in the stability of behavioural regulation in preterm and fullterm infants.     

Fetal Alcohol Spectrum Disorders: Neuropsychological and Behavioral Features

Heavy prenatal alcohol exposure can cause alterations to the developing brain. The resulting neurobehavioral deficits seen following this exposure are wide-ranging and potentially devastating and, therefore, are of significant concern to individuals, families, communities, and society. These effects occur on a continuum, and qualitatively similar neuropsychological and behavioral features are seen across the spectrum of effect. The term fetal alcohol spectrum disorders (FASD) has been used to emphasize the continuous nature of the outcomes of prenatal alcohol exposure, with fetal alcohol syndrome (FAS) representing one point on the spectrum. This paper will provide a comprehensive review of the neuropsychological and behavioral effects of heavy prenatal alcohol exposure, including a discussion of the emerging neurobehavioral profile. Supporting studies of lower levels of exposure, brain-behavior associations, and animal model systems will be included when appropriate.     

Maternal Depression and Youth Internalizing and Externalizing Symptomatology: Severity and Chronicity of Past Maternal Depression and Current Maternal Depressive Symptoms

Maternal depression is a well-documented risk factor for youth depression, and taking into account its severity and chronicity may provide important insight into the degree of risk conferred. This study explored the degree to which the severity/chronicity of maternal depression history explained variance in youth internalizing and externalizing symptoms above and beyond current maternal depressive symptoms among 171 youth (58 % male) ages 8 to 12 over a span of 3 years. Severity and chronicity of past maternal depression and current maternal depressive symptoms were examined as predictors of parent-reported youth internalizing and externalizing symptomatology, as well as youth self-reported depressive symptoms. Severity and chronicity of past maternal depression did not account for additional variance in youth internalizing and externalizing symptoms at Time 1 beyond what was accounted for by maternal depressive symptoms at Time 1. Longitudinal growth curve modeling indicated that prior severity/chronicity of maternal depression predicted levels of youth internalizing and externalizing symptoms at each time point when controlling for current maternal depressive symptoms at each time point. Chronicity of maternal depression, apart from severity, also predicted rate of change in youth externalizing symptoms over time. These findings highlight the importance of screening and assessing for current maternal depressive symptoms, as well as the nature of past depressive episodes. Possible mechanisms underlying the association between severity/chronicity of maternal depression and youth outcomes, such as residual effects from depressive history on mother–child interactions, are discussed.     

Imaging the Impact of Prenatal Alcohol Exposure on the Structure of the Developing Human Brain

Prenatal alcohol exposure has numerous effects on the developing brain, including damage to selective brain structure. We review structural magnetic resonance imaging (MRI) studies of brain abnormalities in subjects prenatally exposed to alcohol. The most common findings include reduced brain volume and malformations of the corpus callosum. Advanced methods have been able to detect shape, thickness and displacement changes throughout multiple brain regions. The teratogenic effects of alcohol appear to be widespread, affecting almost the entire brain. The only region that appears to be relatively spared is the occipital lobe. More recent studies have linked cognition to the underlying brain structure in alcohol-exposed subjects, and several report patterns in the severity of brain damage as it relates to facial dysmorphology or to extent of alcohol exposure. Future studies exploring relationships between brain structure, cognitive measures, dysmorphology, age, and other variables will be valuable for further comprehending the vast effects of prenatal alcohol exposure and for evaluating possible interventions.     

Offspring Effects of Prenatal Alcohol Exposure from Birth to 25 Years: The Seattle Prospective Longitudinal Study

Before alcohol was generally known to cause birth defects, NIAAA in 1974 began funding a population-based Seattle study on alcohol use and pregnancy outcome. Women receiving prenatal care by mid-pregnancy were recruited (N = 1,529) and interviewed at home. Approximately 500 offspring exposed to a range of alcohol levels were examined on 11 occasions between day 1 and 25 years. Neuropsychological and neurobehavioral performance measures are correlated with prenatal alcohol dose, without substantial confounding by socio-demographic or rearing conditions, smoking, nutrition, or other drugs. Deficits in attention, arithmetic skill, spatial-visual memory, and IQ, as well as increased alcohol problems and psychiatric disorders are among offspring outcomes correlated at several ages with maternal drinking during and before pregnancy recognition. Findings are not confined to women who believed they had alcohol problems. Not all exposed offspring appear affected.