ArticleLiterature Review

The Plausibility of Maternal Nutritional Status Being a Contributing Factor to the Risk for Fetal Alcohol Spectrum Disorders: The Potential Influence of Zinc Status as an Example

March 2010
BioFactors 36(2):125-35

DOI:10.1002/biof.89

Source
PubMed

Authors:

Carl L Keen

University of California, Davis

Jan Uriu-Adams

University of California, Davis

Anatoly Skalny

Peoples' Friendship University of Russia

Andrei Grabeklis

I.M. Sechenov First Moscow State Medical University

Show all 9 authorsHide

There is increasing evidence that human pregnancy outcome can be significantly compromised by suboptimal maternal nutritional status. Poor diet results in a maternal-fetal environment in which the teratogenicity of other insults such as alcohol might be amplified. As an example, there is evidence that zinc (Zn) can interact with maternal alcohol exposure to influence the risk for fetal alcohol spectrum disorders (FASD). Studies with experimental animals have shown that the teratogenicity of alcohol is increased under conditions of Zn deficiency, whereas its teratogenicity is lessened when animals are given Zn-supplemented diets or Zn injections before the alcohol exposure. Alcohol can precipitate an acute-phase response, resulting in a subsequent increase in maternal liver metallothionein, which can sequester Zn and lead to decreased Zn transfer to the fetus. Importantly, the teratogenicity of acute alcohol exposure is reduced in metallothionein knockout mice, which can have improved Zn transfer to the conceptus relative to wild-type mice. Consistent with the above, Zn status has been reported to be low in alcoholic women at delivery. Preliminary data from two basic science and clinical nutritional studies that are ongoing as part of the international Collaborative Initiative on Fetal Alcohol Spectrum Disorders support the potential role of Zn, among other nutritional factors, relative to risk for FASD. Importantly, the nutrient levels being examined in these studies are relevant to general clinical populations and represent suboptimal levels rather than severe deficiencies. These data suggest that moderate deficiencies in single nutrients can act as permissive factors for FASD, and that adequate nutritional status or intervention through supplementation may provide protection from some of the adverse effects of prenatal alcohol exposure.

Significance of Selected Environmental and Biological Factors on the Risk of FASD in Women Who Drink Alcohol during Pregnancy

Article

Full-text available

Sep 2023

Prenatal alcohol exposure (PAE), which refers to alcohol consumption by pregnant women, is associated with the risk of numerous severe complications during fetal development. The State Agency for Alcohol Problem Solving reports that the incidence of fetal alcohol spectrum disorder (FASD) in Poland’s general population is over 1.7%, and the incidence of fetal alcohol syndrome (FAS) is estimated at more than 0.5%. This study aimed to evaluate the significance of alcohol exposure and focused on the pattern of alcohol intoxication exhibited by the mother during pregnancy and other environmental factors of the maternal environment contributing to the development of FASD. The study covered 554 subjects, including 251 mothers and 303 children (213 girls and 90 boys). The mother’s drinking problem was determined based on the information obtained from the case history. All children qualified for the study fulfilled the h-PAE (high alcohol exposure) criteria during their fetal life. The clinical diagnosis of FAS and pFAS (occurrence of morphological symptoms of fetal alcohol syndrome) was made using a four-digit diagnostic questionnaire validated in the Polish version of the Washington Questionnaire for the assessment of the spectrum of alcohol-related neurodevelopmental disorders or alcohol-related cognitive impairment (ARND/C). Statistical analysis of the obtained research results was developed using statistical software–STATISTICA PL, version 13.1 (StatSoft, Inc., Szczecin, Poland 2016, STATISTICA–data analysis software system, version 13.1). The most destructive drinking behaviors are compulsive intoxication (BD, binge drinking) during the first 6 weeks of pregnancy and chronic addiction throughout its duration (CHD, chronic drinking). Chronic alcohol intoxication (CHD) leads to a poorer nutritional status in mothers, which is reflected in a lower body mass index (BMI) (<18 kg/m2).

Insights into retinoic acid deficiency and the induction of craniofacial malformations and microcephaly in Fetal Alcohol Spectrum Disorder

Article

Jan 2019

Fetal Alcohol Spectrum Disorder (FASD) is a set of neurodevelopmental malformations caused by maternal consumption of alcohol during pregnancy. FASD sentinel facial features are unique to the disorder and microcephaly is common in severe forms of FASD. Retinoic acid deficiency has been shown to cause craniofacial malformations and microcephaly in animal models reminiscent of those caused by prenatal alcohol exposure. Alcohol exposure affects the migration and survival of cranial neural crest cells, which are required for proper frontonasal prominence and pharyngeal arch development. Defects in craniofacial development are further amplified by the many downstream pathways that are transcriptionally controlled retinoic acid target genes, including Shh signaling. Recent evidence shows that alcohol exposure itself is sufficient to induce retinoic acid deficiency in the embryo. These data suggest that retinoic acid deficiency is an important underlying etiology of FASD. In disorders like Vitamin A Deficiency, FASD, DiGeorge, CHARGE, Smith‐Magenis, Matthew‐Wood and Congenital Zika Syndromes, evidence is accumulating to link reduced retinoic acid signaling with developmental defects like craniofacial malformations and microcephaly. Research focus on characterizing the effects of retinoic acid deficiency during early development and on understanding the downstream signaling pathways involved in aberrant head and craniofacial development will reveal underlying etiologies of these disorders. This article is protected by copyright. All rights reserved.

Postnatal nutritional treatment of neurocognitive deficits in Foetal Alcohol Spectrum Disorder (FASD)

Article

Full-text available

Nov 2017

Ethanol is the most important teratogen agent in humans. Prenatal alcohol exposure can lead to a wide range of adverse effects, which are broadly termed as Foetal Alcohol Spectrum Disorder (FASD). Socioeconomic status, ethnicity, differences in genetic susceptibility related to ethanol metabolism, alcohol consumption patterns, obstetric problems, maternal nutrition, stress, and other co-administered drugs are all factors that may influence FASD manifestations. Recently, much attention has been paid to the role of nutrition as a protective factor against alcohol teratogenicity. There are a great number of papers related to nutritional treatment of nutritional deficits due to several factors associated with maternal consumption of alcohol and with eating and social disorders in FASD children. Although research showed the clinical benefits of nutritional interventions, a minimum number of studies refer to postnatal nutrition treatment of neurodevelopmental deficits. Nutritional supplementation in children with FASD has a dual objective: to overcome nutritional deficiencies and to reverse or improve the cognitive deleterious effects of prenatal alcohol exposure. Further research is necessary to confirm positive results, to determine optimal amounts of nutrients needed in supplementation, and to investigate the collective effects of simultaneous multiple-nutrient supplementation.

Maternal Dietary Intake Among Alcohol-Exposed Pregnancies Is Linked to Early Infant Physical Outcomes in South Africa

Article

Sep 2023

Maternal dietary intake is likely a contributing factor to fetal alcohol spectrum disorders (FASD). Two, 24-hour dietary recalls were completed by pregnant women (n=196) in South African communities with high rates of FASD. More than 50% of all women in this study were below the Estimated Average Requirement for pregnancy for vitamins A, C, D, E, riboflavin, vitamin B6, folate, calcium, magnesium, iron, and zinc. More than 90% of mothers were below the Recommended Dietary Allowance (RDA) or Adequate Intake (AI) for pregnancy on vitamin A, K, D, E, choline, calcium, magnesium, zinc, and potassium. More than 80% were below RDA/AI for pantothenic acid, vitamin B6, and folate. Women who consumed alcohol reported significantly lower intake of calcium and three saturated fatty acids and significantly higher intake of two monounsaturated fatty acids. On average, infants were <40th centile on length, weight, and head circumference at 6 weeks old, regardless of alcohol exposure. Twenty nutrients correlated with at least one measure of 1st trimester drinking (drinks per drinking day, number of drinking days per week, and total drinks per week). Nutrients included four saturated fatty acids, eight amino acids, calcium, B-complex vitamins, choline, and betaine. Calcium correlated with all three drinking measures. Further analyses revealed six nutrients were associated with infant length, weight, and/or head circumference among unexposed infants, and 12 nutrients were associated among infants with prenatal alcohol exposure. Inadequate maternal dietary intake, with alcohol exposure, may increase risk for poor infant growth and likelihood of FASD in this population.

Essential trace elements in neurodevelopment: An updated narrative

Chapter

Jan 2023

Nutritional Status Differs by Prescription Opioid Use among Women of Reproductive Age: NHANES 1999–2018

Article

Full-text available

Apr 2023

Prescription opioid use among pregnant women has increased in recent years. Prenatal exposure to opioids and poor nutrition can both negatively impact maternal–fetal outcomes. The objective of this study was to characterize the nutrition and health status of reproductive-age women taking prescription opioids, compared to women not taking opioids. Using NHANES 1999–2018 data, non-pregnant women aged 20–44 years were classified as taking a prescription opioid in the last 30 days (n = 404) or unexposed controls (n = 7234). Differences in anthropometric, cardiovascular, hematologic, and micronutrient status indicators between opioid-exposed and unexposed women were examined. Opioid-exposed women were older, had lower income and education, and were more likely to be non-Hispanic White, to smoke, and to have chronic health conditions compared to unexposed women. In unadjusted analyses, several nutrition and health markers were significantly different between opioid exposure groups. After controlling for covariates, women taking opioids had higher odds of Class II (OR = 1.6, 95% CI = 1.1–2.3) or III obesity (OR = 1.6, 95% CI = 1.1–2.5), and lower levels of serum folate, iron, and transferrin saturation. Reproductive-age women taking prescription opioids may be at risk for poorer nutritional and cardiometabolic health. Future research is needed to explore whether nutritional status impacts maternal–fetal outcomes for women exposed to opioids during pregnancy.

Fetal alcohol spectrum disorders

Article

Feb 2023

Alcohol readily crosses the placenta and may disrupt fetal development. Harm from prenatal alcohol exposure (PAE) is determined by the dose, pattern, timing and duration of exposure, fetal and maternal genetics, maternal nutrition, concurrent substance use, and epigenetic responses. A safe dose of alcohol use during pregnancy has not been established. PAE can cause fetal alcohol spectrum disorders (FASD), which are characterized by neurodevelopmental impairment with or without facial dysmorphology, congenital anomalies and poor growth. FASD are a leading preventable cause of birth defects and developmental disability. The prevalence of FASD in 76 countries is >1% and is high in individuals living in out-of-home care or engaged in justice and mental health systems. The social and economic effects of FASD are profound, but the diagnosis is often missed or delayed and receives little public recognition. Future research should be informed by people living with FASD and be guided by cultural context, seek consensus on diagnostic criteria and evidence-based treatments, and describe the pathophysiology and lifelong effects of FASD. Imperatives include reducing stigma, equitable access to services, improved quality of life for people with FASD and FASD prevention in future generations. Fetal alcohol spectrum disorders (FASD) are characterized by neurodevelopmental impairment with or without facial dysmorphology, congenital anomalies and poor growth. This Primer discusses the epidemiology, pathophysiology, diagnosis and treatment of FASD.

Genetic Influences on Fetal Alcohol Spectrum Disorder

Article

Full-text available

Jan 2023

Fetal alcohol spectrum disorder (FASD) encompasses the range of deleterious outcomes of prenatal alcohol exposure (PAE) in the affected offspring, including developmental delay, intellectual disability, attention deficits, and conduct disorders. Several factors contribute to the risk for and severity of FASD, including the timing, dose, and duration of PAE and maternal factors such as age and nutrition. Although poorly understood, genetic factors also contribute to the expression of FASD, with studies in both humans and animal models revealing genetic influences on susceptibility. In this article, we review the literature related to the genetics of FASD in humans, including twin studies, candidate gene studies in different populations, and genetic testing identifying copy number variants. Overall, these studies suggest different genetic factors, both in the mother and in the offspring, influence the phenotypic outcomes of PAE. While further work is needed, understanding how genetic factors influence FASD will provide insight into the mechanisms contributing to alcohol teratogenicity and FASD risk and ultimately may lead to means for early detection and intervention.

Untargeted Metabolome Analysis of Alcohol-Exposed Pregnancies Reveals Metabolite Differences That Are Associated with Infant Birth Outcomes

Article

Full-text available

Dec 2022

Prenatal alcohol exposure can produce offspring growth deficits and is a leading cause of neurodevelopmental disability. We used untargeted metabolomics to generate mechanistic insight into how alcohol impairs fetal development. In the Western Cape Province of South Africa, 52 women between gestational weeks 5–36 (mean 18.5 ± 6.5) were recruited, and they provided a finger-prick fasting bloodspot that underwent mass spectrometry. Metabolomic data were analyzed using partial least squares-discriminant analyses (PLS-DA) to identify metabolites that correlated with alcohol exposure and infant birth outcomes. Women who consumed alcohol in the past seven days were distinguished by a metabolite profile that included reduced sphingomyelins, cholesterol, and pregnenolones, and elevated fatty acids, acyl and amino acyl carnitines, and androsterones. Using PLS-DA, 25 of the top 30 metabolites differentiating maternal groups were reduced by alcohol with medium-chain free fatty acids and oxidized sugar derivatives having the greatest influence. A separate ortho-PLS-DA analysis identified a common set of 13 metabolites that were associated with infant length, weight, and head circumference. These included monoacylglycerols, glycerol-3-phosphate, and unidentified metabolites, and most of their associations were negative, implying they represent processes having adverse consequences for fetal development.

Fetal Alcohol Spectrum Disorder and Iron Homeostasis

Article

Full-text available

Oct 2022

Prenatal alcohol exposure results in a spectrum of behavioral, cognitive, and morphological abnormalities collectively referred to as fetal alcohol spectrum disorder (FASD). FASD presents with significant phenotypic variability and may be modified by gestational variables such as maternal nutritional status. Iron serves a critical function in the development of and processes within central nervous system (CNS) structures. Gestational iron deficiency alters CNS development and may contribute to neurodevelopmental impairment in FASD. This review explores the relationship between iron deficiency and fetal alcohol spectrum disorder as described in small animal and human studies. Consideration is given to the pathophysiologic mechanisms linking iron homeostasis and prenatal alcohol exposure. Existing data suggest that iron deficiency contributes to the severity of FASD and provide a mechanistic explanation linking these two conditions.

Dietary Intake Patterns and Lifestyle Behaviors of Pregnant Women Living in a Manitoba First Nations Community: Implications for Fetal Alcohol Spectrum Disorder

Article

Full-text available

Aug 2022

The information on the nutrition status of women at-risk of carrying a child with fetal alcohol spectrum disorder (FASD) is scarce, particularly in the First Nations population living on reserve. This study examined and compared nutrition status, dietary intake, and lifestyle patterns of pregnant at-risk, defined as those who consume alcoholic drink during the current pregnancy, and non-at-risk women living in northern Manitoban community. Thirty-seven pregnant, First Nations women (at-risk n = 15; non-at-risk, n = 22) were recruited to participate in the study. A questionnaire, presented in paper and iPad formats, collected information on participants' demographics, dietary intake, lifestyle, pregnancy outcomes, and maternal health. A food frequency questionnaire and 24-h recall were used to determine nutrient intake. Nutrient values were assessed using Dietary Reference Intakes (DRI). At-risk and non-at-risk women were below the Canada Food Guide serving size recommended for Vegetable and Fruit, Grain, and Milk Products with 93%, 92%, and 93% of participants not meeting the recommendations, respectively. Women met the recommendations for vitamins A, B1, B12, C, niacin, choline, as well as calcium, and zinc. Sixty eight percentage (%) of participants did not meet the recommendations for folate and iron, and 97% for docosahexaenoic acid (DHA). Significant differences were observed between non-at-risk and at-risk women for mean % DRI intakes of vitamin C (313 ± 224 vs. 172 ± 81 mg/day), niacin (281 ± 123 vs. 198 ± 80 mg/day), folate (70 ± 38 vs. 10 ± 22 mcg/day), and iron (101 ± 74 vs. 74 ± 30 mg/day). The findings of this study lay a fundamental premise for the development of community nutrition programs, nutrition education, and nutrition intervention, such as community specific prenatal supplementation. These will assist in ensuring adequate maternal nutrient intake and benefit families and communities in Northern Manitoba with and without alcohol insult.

Epigenetics of pregnancy: looking beyond the DNA code

Article

Full-text available

Apr 2022
J ASSIST REPROD GEN

Epigenetics is the branch of genetics that studies the different mechanisms that influence gene expression without direct modification of the DNA sequence. An ever-increasing amount of evidence suggests that such regulatory processes may play a pivotal role both in the initiation of pregnancy and in the later processes of embryonic and fetal development, thus determining long-term effects even in adult life. In this narrative review, we summarize the current knowledge on the role of epigenetics in pregnancy, from its most studied and well-known mechanisms to the new frontiers of epigenetic regulation, such as the role of ncRNAs and the effects of the gestational environment on fetal brain development. Epigenetic mechanisms in pregnancy are a dynamic phenomenon that responds both to maternal–fetal and environmental factors, which can influence and modify the embryo-fetal development during the various gestational phases. Therefore, we also recapitulate the effects of the most notable environmental factors that can affect pregnancy and prenatal development, such as maternal nutrition, stress hormones, microbiome, and teratogens, focusing on their ability to cause epigenetic modifications in the gestational environment and ultimately in the fetus. Despite the promising advancements in the knowledge of epigenetics in pregnancy, more experience and data on this topic are still needed. A better understanding of epigenetic regulation in pregnancy could in fact prove valuable towards a better management of both physiological pregnancies and assisted reproduction treatments, other than allowing to better comprehend the origin of multifactorial pathological conditions such as neurodevelopmental disorders.

Alcohol use during pregnancy in rural Lesotho: “There is nothing else except alcohol”

Article

Dec 2021

Objective Reducing alcohol use during pregnancy is a pressing public health priority in Sub-Saharan Africa, but insight into the factors that influence prenatal drinking practices is lacking. This study investigated perceptions of, and motivations for, alcohol consumption during pregnancy and associated practices in a rural district of Lesotho. Methods A combination of purposive and snowball sampling methods were used to identify pregnant women and mothers with young children from the general community, as well as from alcohol-serving venues. Between September 2016 and March 2017, a trained data collector conducted in-depth interviews with 40 women on reasons why pregnant women drink, what they know about the risk of drinking alcohol during pregnancy, and perceptions of women who drink during pregnancy. Results Sixty-five percent of women (n = 26) reported that they consumed alcohol during pregnancy. Findings were clustered into four themes: 1) alcohol use in daily and cultural life; 2) alcohol as relief from stress and hunger; 3) alcohol's effect on the baby; and 4) access to information about alcohol consumption. Our data suggest that alcohol use was a prominent feature of daily life and a key part of traditional events and ceremonies. Other than potentially harming the baby through falling on their stomachs while inebriated, women did not mention other risks associated with prenatal alcohol use. Rather, there were prominent beliefs that drinking alcohol – home-brewed alcohol in particular – had cleansing or protective benefits for the baby. Experiences of food insecurity were prominent, and women reported that alcohol helped curb their hunger and allowed them to save food to give to their children. Conclusions Within this context of chronic poverty and food insecurity, alcohol use during pregnancy will continue to represent a valid, though tragic choice if the structural conditions and current social arrangements that facilitate prenatal alcohol use remain unchanged.

Alcohol’s Impact on the Fetus

Article

Full-text available

Sep 2021

Background: Alcohol is a teratogen and prenatal exposure may adversely impact the developing fetus, increasing risk for negative outcomes, including Fetal Alcohol Spectrum Disorder (FASD). Global trends of increasing alcohol use among women of childbearing age due to economic development, changing gender roles, increased availability of alcohol, peer pressure and social acceptability of women's alcohol use may put an increasing number of pregnancies at risk for prenatal alcohol exposure (PAE). This risk has been exacerbated by the ongoing COVID-19 pandemic in some countries. Method: This literature review presents an overview on the epidemiology of alcohol use among childbearing age and pregnant women and FASD by World Health Organization regions; impact of PAE on fetal health, including FASD; associated comorbidities; and social outcomes. Results/conclusion: The impact of alcohol on fetal health and social outcomes later in life is enormous, placing a huge economic burden on countries. Prevention of prenatal alcohol exposure and early identification of affected individuals should be a global public health priority.

Gestational zinc deficiency impairs brain astrogliogenesis in rats through multistep alterations of the JAK/STAT3 signaling pathway

Article

Full-text available

May 2021

We previously showed that zinc (Zn) deficiency affects the STAT3 signaling pathway in part through redox-regulated mechanisms. Given that STAT3 is central to the process of astrogliogenesis, this study investigated the consequences of maternal marginal Zn deficiency on the developmental timing and key mechanisms of STAT3 activation, and its consequences on astrogliogenesis in the offspring. This work characterized the temporal profile of cortical STAT3 activation from the mid embryonic stage up to young adulthood in the offspring from dams fed a marginal Zn deficient diet (MZD) throughout gestation and until postnatal day (P) 2. All rats were fed a Zn sufficient diet (control) from P2 until P56. Maternal zinc deficiency disrupted cortical STAT3 activation at E19 and P2. This was accompanied by altered activation of JAK2 kinase due to changes in PTP1B phosphatase activity. The underlying mechanisms mediating the adverse impact of a decreased Zn availability on STAT3 activation in the offspring brain include: (i) impaired PTP1B degradation via the ubiquitin/proteasome pathway; (ii) tubulin oxidation, associated decreased interactions with STAT3 and consequent impaired nuclear translocation; and (iii) decreased nuclear STAT3 acetylation. Zn deficiency-associated decreased STAT3 activation adversely impacted astrogliogenesis, leading to a lower astrocyte number in the early postnatal and adult brain cortex. Thus, a decreased availability of Zn during early development can have a major and irreversible adverse effect on astrogliogenesis, in part via multistep alterations in the STAT3 pathway.

Neuroimaging of Supraventricular Frontal White Matter in Children with Familial Attention-Deficit Hyperactivity Disorder and Attention-Deficit Hyperactivity Disorder Due to Prenatal Alcohol Exposure

Article

Full-text available

Aug 2021
NEUROTOX RES

Attention-deficit hyperactivity disorder (ADHD) is common in patients with (ADHD+PAE) and without (ADHD-PAE) prenatal alcohol exposure (PAE). Many patients diagnosed with idiopathic ADHD actually have covert PAE, a treatment-relevant distinction. To improve differential diagnosis, we sought to identify brain differences between ADHD+PAE and ADHD-PAE using neurobehavioral, magnetic resonance spectroscopy, and diffusion tensor imaging metrics that had shown promise in past research. Children 8–13 were recruited in three groups: 23 ADHD+PAE, 19 familial ADHD-PAE, and 28 typically developing controls (TD). Neurobehavioral instruments included the Conners 3 Parent Behavior Rating Scale and the Delis-Kaplan Executive Function System (D-KEFS). Two dimensional magnetic resonance spectroscopic imaging was acquired from supraventricular white matter to measure N-acetylaspartate compounds, glutamate, creatine + phosphocreatine (creatine), and choline-compounds (choline). Whole brain diffusion tensor imaging was acquired and used to to calculate fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity from the same superventricular white matter regions that produced magnetic resonance spectroscopy data. The Conners 3 Parent Hyperactivity/Impulsivity Score, glutamate, mean diffusivity, axial diffusivity, and radial diffusivity were all higher in ADHD+PAE than ADHD-PAE. Glutamate was lower in ADHD-PAE than TD. Within ADHD+PAE, inferior performance on the D-KEFS Tower Test correlated with higher neurometabolite levels. These findings suggest white matter differences between the PAE and familial etiologies of ADHD. Abnormalities detected by magnetic resonance spectroscopy and diffusion tensor imaging co-localize in supraventricular white matter and are relevant to executive function symptoms of ADHD.

Infant Cardiac Orienting Responses Predict Later FASD in the Preschool Period

Article

Dec 2020

Background Prenatal alcohol exposure (PAE) has been identified as one of the leading preventable causes of developmental disabilities but early identification of those impacted has been challenging. This study evaluated the use of infant cardiac orienting responses (CORs), which assess neurophysiological encoding of environmental events and are sensitive to the impact of PAE, to predict later Fetal Alcohol Spectrum Disorder (FASD) status. Methods Mother‐infant dyads from Ukraine were recruited during pregnancy based on the mother’s use of alcohol. Participants (n = 120) were then seen at 6 and 12 months when CORs were collected and in the preschool period when they were categorized as having (1) fetal alcohol syndrome (FAS), (2) partial FAS (pFAS), (3) alcohol‐related neurodevelopmental disorder (ARND), (4) PAE and no diagnosis, or (5) no PAE and no diagnosis. To assess CORs, stimuli (auditory tones and pictures) were presented using a fixed‐trial habituation/dishabituation paradigm. Heart rate (HR) responses were aggregated across the first 3 habituation and dishabituation trials and converted to z‐scores relative to the sample’s mean response at each second by stimuli. Z‐scores greater than 1 were then counted by condition (habituation or dishabituation) to compute a total risk index. Results Significant group differences were found on total deviation scores of the CORs elicited from visual but not auditory stimuli. Those categorized as pFAS/FAS had significantly higher total deviation scores than did those categorized as ARND or as having no alcohol‐related diagnosis with or without a history of PAE. Receiver operating characteristic curve analysis of the visual response yielded an area under the curve value of .765 for predicting to pFAS/FAS status. Conclusions A score reflecting total deviation from typical HR during CORs elicited using visual stimuli in infancy may be useful in identifying individuals who need early intervention as a result of their PAE.

Relationship between concentrations of elements and geographic location in Poland

Article

Full-text available

May 2020

Introduction. Interactions occur between concentrations of metals in the human body and the environment in various geographic locations, which can be of importance for both the proper development and the course of pregnancy. Objective. The aim of the study was to assess the concentrations of Zn, Cu and Cd and Zn:Cu and Zn:Cd molar ratios in the placenta, umbilical cord and in the foetal membrane, and to examine the relationship between concentrations of these elements and the place of residence. Materials and method. The research material was obtained from 99 healthy women from north-western and central Poland. Data for the study were collected from the medical history and documents of admission to the ward and documents confirming the birth of the newborn. Concentrations of zinc (Zn), copper (Cu) and cadmium (Cd) were determined using the ICP–AES method (spectrophotometry of atomic absorption) in inductively coupled argon plasma. Results. The average concentration of Zn, Cu and Cd in afterbirths was ~ 0.01 mg/kg of dry weight (dw). In central Poland, the results revealed a significant increase in zinc in the membrane (OR=1.098, p=0.002), cadmium in the placenta (OR=1.324, p=0.006), Zn:Cu in the membrane (OR=1.012, p<0.001). In north-western Poland, an increase in copper in the membrane (OR=1.239, p=0.025) was revealed. Conclusions. The use biological materials, such as the placenta, foetal membrane and umbilical cord to assess exposure to heavy metals and necessary elements is justified.

Altered Maternal Plasma Fatty Acid Composition by Alcohol Consumption and Smoking during Pregnancy and Associations with Fetal Alcohol Spectrum Disorders

Article

Full-text available

Apr 2020

Objective: Polyunsaturated fatty acids are vital for optimal fetal neuronal development. The relationship between maternal alcohol consumption and smoking with third trimester plasma fatty acids were examined and their association with Fetal Alcohol Spectrum Disorders (FASD). Methods: Moderate to heavy alcohol-using and low/unexposed comparison women were recruited during mid-pregnancy from two prenatal clinics in Ukraine. The participants’ infants underwent physical and neurobehavioral exams prior to one-year of age and classified as having FASD by maternal alcohol consumption and neurobehavioral scores. A subset of mother-child pairs was selected representing three groups of cases and controls: Alcohol-Exposed with FASD (AE-FASD, n = 30), Alcohol-Exposed Normally Developing (AE-ND, n = 33), or Controls (n = 46). Third trimester maternal plasma samples were analyzed for fatty acids and levels were compared across groups. Results: The percent of C18:0 (p < 0.001), arachidonic acid (AA, C20:4n-6, p = 0.017) and C22:5n-6 (p = 0.001) were significantly higher in AE-FASD women than controls or AE-ND women. Alcohol-exposed women who smoked had lower C22:5n-3 (p = 0.029) and docosahexaenoic acid (DHA, C22:6n-3, p = 0.005) and higher C22:5n-6 (p = 0.013) than women consuming alcohol alone or abstainers. Conclusion: Alterations in fatty acid profiles were observed in moderate to heavy alcohol-consuming mothers with infants classified with FASD compared to alcohol-exposed normally developing infants or controls.

Prenatal alcohol exposure is associated with early motor, but not language development in a South African cohort

Article

Full-text available

Jan 2020

Objective To investigate the association of prenatal alcohol exposure (PAE) and early neurodevelopment in the first 2 years of life, adjusting for maternal sociodemographic and psychosocial factors, in the Drakenstein Child Health Study (DCHS), a South African birth cohort study. Methods The DCHS comprises a population-based birth cohort of 1143 children, of which, a subsample completed the Bayley Scales of Infant Development-III (BSID-III) at 6 (n = 260) and 24 months of age (n = 734). A subset of alcohol exposed, and unexposed children was included in this analysis at age 6 months (n = 52 exposed; n = 104 unexposed) and 24 months (n = 92 exposed; n=184 unexposed). Multiple hierarchical regression was used to explore the associations of PAE with motor and language development. Results PAE was significantly associated with decreased gross motor (OR = 0.16, 95%CI 0.06-0.44, p = 0.001) or fine motor (OR = 0.16, 95%CI 0.06-0.46, p = 0.001) functioning after adjusting for maternal sociodemographic and psychosocial factors at 6 months of age only. No significant effects were found in either receptive or expressive communication and cognitive outcomes at either time point. Conclusion PAE has potentially important consequences for motor development in the first 2 years of life, a period during which the most rapid growth and maturation occurs. These findings highlight the importance of identifying high-risk families in order to provide preventive interventions, particularly in antenatal clinics and early intervention services.

Reduced hepatic metallothionein expression in first trimester fetuses in response to intrauterine smoking exposure: a consequence of low maternal zinc levels?

Article

Nov 2019
HUM REPROD

Study question: Does maternal smoking in early pregnancy affect metallothionein 1 and 2 (MT1 and MT2) mRNA and protein expression in first trimester placenta or embryonic/fetal liver? Summary answer: In the first trimester, MT protein expression is seen only in liver, where smoking is associated with a significantly reduced expression. What is known already: Zinc homeostasis is altered by smoking. Smoking induces MT in the blood of smokers properly as a result of the cadmium binding capacities of MT. In term placenta MT is present and smoking induces gene and protein expression (MT2 in particular), but the MT presence and response to smoking have never been examined in first trimester placenta or embryonic/fetal tissues. Study design, size, duration: Cross sectional study where the presence of MT mRNA and protein was examined at the time of the abortion. The material was collected with informed consent after surgical intervention and frozen immediately. For protein expression analysis, liver tissue originating from smoking exposed n = 10 and unexposed n = 12 pregnancies was used. For mRNA expression analyses, placental tissue originating from smokers n = 19 and non-smokers n = 23 and fetal liver tissue from smoking exposed n = 16 and smoking unexposed pregnancies n = 13, respectively, were used. Participants/materials, setting, methods: Tissues were obtained from women who voluntarily and legally chose to terminate their pregnancy between gestational week 6 and 12. Western blot was used to determine the protein expression of MT, and real-time PCR was used to quantify the mRNA expression of MT2A and eight MT1 genes alongside the expression of key placental zinc transporters: zinc transporter protein-1 (ZNT1), Zrt-, Irt-related protein-8 and -14 (ZIP8 and ZIP14). Main results and the role of chance: A significant reduction in the protein expression of MT1/2 in liver tissue (P = 0.023) was found by western blot using antibodies detecting both MT forms. Overall, a similar tendency was observed on the mRNA level although not statistically significant. Protein expression was not present in placenta, but the mRNA regulation suggested a down regulation of MT as well. A suggested mechanism based on the known role of MT in zinc homeostasis could be that the findings reflect reduced levels of easily accessible zinc in the blood of pregnant smokers and hence a reduced MT response in smoking exposed fetal/embryonic tissues. Limitations and reasons for caution: Smoking was based on self-reports; however, our previous studies have shown high consistency regarding cotinine residues and smoking status. Passive smoking could interfere but was found mainly among smokers. The number of fetuses was limited, and other factors such as medication and alcohol might affect the findings. Information on alcohol was not consistently obtained, and we cannot exclude that it was more readily obtained from non-users. In the study, alcohol consumption was reported by a limited number (less than 1 out of 5) of women but with more smokers consuming alcohol. However, the alcohol consumption reported was typically limited to one or few times low doses. The interaction between alcohol and smoking is discussed in the paper. Notably we would have liked to measure zinc status to test our hypothesis, but maternal blood samples were not available. Wider implications of the findings: Zinc deficiency-in particular severe zinc deficiency-can affect pregnancy outcome and growth. Our findings indicate that zinc homeostasis is also affected in early pregnancy of smokers, and we know from pilot studies that even among women who want to keep their babies, the zinc status is low. Our findings support that zinc supplements should be considered in particular to women who smoke. Study funding/competing interest(s): We thank the Department of Biomedicine for providing laboratory facilities and laboratory technicians and the Lundbeck Foundation and Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis Legat for financial support. The authors have no competing interests to declare. Trial registration number: N/A.

The causal web of foetal alcohol spectrum disorders: a review and causal diagram

Article

Full-text available

May 2020
EUR CHILD ADOLES PSY

Foetal alcohol spectrum disorders (FASDs) are a leading cause of developmental disability. Prenatal alcohol use is the sole necessary cause of FASD, but it is not always sufficient. Multiple factors influence a child’s susceptibility to FASD following prenatal alcohol exposure. Much of the FASD risk factor literature has been limited to discussions of association, rather than causation. While knowledge of predictor variables is important for identifying who is most at risk of FASD and for targeting interventions, causal knowledge is important for identifying effective mechanisms for prevention and intervention programmes. We conducted a systematic search and narrative synthesis of the evidence and used this to create a causal diagram (directed acyclic graph; DAG) to describe the causal pathways to FASD. Our results show that the aetiology of FASD is multifaceted and complex. FASD risk is determined by a range of lifestyle, sociodemographic, maternal, social, gestational, and genetic factors. The causal diagram that we present in this review provides a comprehensive summary of causal risk factors for FASD and can be used as a tool to inform data collection and statistical modelling strategies to minimise bias in future studies of FASD.

Prenatal alcohol use as a risk for attention-deficit/hyperactivity disorder

Article

Full-text available

Sep 2019
EUR ARCH PSY CLIN N

The objective of the study was to investigate the association between alcohol use during pregnancy and mental disorders in childhood, controlling for confounding risk factors by a longitudinal study of pregnant women and their offspring. The initial cohort comprised pregnant women attending an obstetric service. From the initial sample of 449 pregnant women, 81 mother–child pairs agreed to participate. After 12 years, mother–child pairs were assessed through self-administered questionnaires and semi-structured interviews. The Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children—Present and Lifetime Version (K-SADS-PL) was used to assess the presence of any mental disorders in the children. The mothers were assessed by the Self-Reporting Questionnaire (SRQ) and the Alcohol Use Disorders Identification Test (AUDIT). Furthermore, data on the mother’s alcohol use collected during pregnancy were analysed. A logistic regression tested the influence of alcohol consumption in all trimesters and binge drinking on the occurrence of attention-deficit/hyperactivity disorder (ADHD), controlling for covariates. Binge drinking at any time during pregnancy or low–moderate alcohol consumption in all trimesters of pregnancy was associated with a fivefold increased odds of child ADHD. The combination of both patterns of alcohol use added an increase of 19% in the variance of ADHD’s occurrence. The episodic use of at least four drinks or the regular use of low–moderate alcohol doses during pregnancy was associated with significantly increased odds of subsequent child ADHD. Reducing binge drinking and regular alcohol use of pregnant women may lead to a significant decrease in their children developing ADHD.

Quality of Prenatal and Childhood Diet Predicts Neurodevelopmental Outcomes among Children in Mexico City

Article

Full-text available

Aug 2018

Adequate nutrition is important for neurodevelopment. Although nutrients are ingested in combination, the impact of specific nutrients within the context of a nutrient mixture has not been studied with respect to health, such as neurodevelopment. Therefore, we examined the impact of prenatal and childhood nutrient mixtures on neurodevelopmental outcomes. Participants included mother–child pairs in the Programming Research in Obesity, Growth, Environment, and Social Stress (PROGRESS) prospective birth cohort in Mexico City. We assessed prenatal and child micro- and macronutrient profiles among 65 and 329 children, respectively, via food frequency questionnaires. Neurodevelopmental outcomes of 4–6-year-old children were measured using the McCarthy Scales of Children’s Abilities (MSCA). We conducted weighted quantile sum (WQS) regression analyses to calculate indices reflecting “good” and “poor” prenatal and childhood nutrition. After adjusting for maternal education, socioeconomic status, the Home Observation for Measurement of the Environment (HOME) score, and total caloric intake, the good prenatal and childhood nutrition indices predicted more favorable neurodevelopment, while both poor nutrition indices predicted poorer neurodevelopment. These associations were stronger in prenatal than childhood models. Monounsaturated fats predicted various neurodevelopmental abilities relatively strongly in both models. Prenatal and childhood consumption of combinations of beneficial nutrients may contribute to more favorable neurodevelopment.

The Effects of Alcohol and Drugs of Abuse on Maternal Nutritional Profile during Pregnancy

Article

Full-text available

Aug 2018

The consumption of alcohol and drugs of abuse among pregnant women has experienced a significant increase in the last decades. Suitable maternal nutritional status is crucial to maintain the optimal environment for fetal development but if consumption of alcohol or drugs of abuse disrupt the intake of nutrients, the potential teratogenic effects of these substances increase. Despite evidence of the importance of nutrition in addicted pregnant women, there is a lack of information on the effects of alcohol and drugs of abuse on maternal nutritional status; so, the focus of this review was to provide an overview on the nutritional status of addicted mothers and fetuses. Alcohol and drugs consumption can interfere with the absorption of nutrients, impairing the quality and quantity of proper nutrient and energy intake, resulting in malnutrition especially of micronutrients (vitamins, omega–3, folic acid, zinc, choline, iron, copper, selenium). When maternal nutritional status is compromised by alcohol and drugs of abuse the supply of essential nutrients are not available for the fetus; this can result in fetal abnormalities like Intrauterine Growth Restriction (IUGR) or Fetal Alcohol Spectrum Disorder (FASD). It is critical to find a strategy to reduce fetal physical and neurological impairment as a result of prenatal alcohol and drugs of abuse exposure combined with poor maternal nutrition. Prenatal nutrition interventions and target therapy are required that may reverse the development of such abnormalities.

Physical Development of Young Children Born by Alcohol Drinking Mothers

Article

Full-text available

Jan 2018

Maternal Iron Nutriture as a Critical Modulator of FASD Risk in Alcohol-Exposed Pregnancies

Article

Full-text available

Oct 2017

Alcohol consumption during pregnancy places the fetus at risk for permanent physical, cognitive, and behavioral impairments, collectively termed fetal alcohol spectrum disorders (FASD). However, prenatal alcohol exposure (PAE) outcomes vary widely, and growing evidence suggests that maternal nutrition is a modifying factor. Certain nutrients, such as iron, may modulate FASD outcomes. Untreated gestational iron deficiency (ID) causes persistent neurodevelopmental deficits in the offspring that affect many of the same domains damaged by PAE. Although chronic alcohol consumption enhances iron uptake and elevates liver iron stores in adult alcoholics, alcohol-abusing premenopausal women often have low iron reserves due to menstruation, childbirth, and poor diet. Recent investigations show that low iron reserves in during pregancy are strongly associated with a worsening of several hallmark features in FASD including reduced growth and impaired associative learning. This review discusses recent clinical and animal model findings that maternal ID worsens fetal outcomes in response to PAE. It also discusses underlying mechanisms by which PAE disrupts maternal and fetal iron homeostasis. We suggest that alcohol-exposed, ID pregnancies contribute to the severe end of the FASD spectrum.

Acute maternal oxidant exposure causes susceptibility of the fetal brain to inflammation and oxidative stress

Article

Full-text available

Sep 2017
J NEUROINFLAMM

Background Maternal exposure to environmental stressors poses a risk to fetal development. Oxidative stress (OS), microglia activation, and inflammation are three tightly linked mechanisms that emerge as a causal factor of neurodevelopmental anomalies associated with prenatal ethanol exposure. Antioxidants such as glutathione (GSH) and CuZnSOD are perturbed, and their manipulation provides evidence for neuroprotection. However, the cellular and molecular effects of GSH alteration in utero on fetal microglia activation and inflammation remain elusive. Methods Ethanol (EtOH) (2.5 g/kg) was administered to pregnant mice at gestational days 16–17. One hour prior to ethanol treatment, N-acetylcysteine (NAC) and L-buthionine sulfoximine (BSO) were administered to modulate glutathione (GSH) content in fetal and maternal brain. Twenty-four hours following ethanol exposure, GSH content and OS in brain tissues were analyzed. Cytokines and chemokines were selected based on their association with distinctive microglia phenotype M1-like (IL-1β, IFN γ, IL-6, CCL3, CCL4, CCL-7, CCL9,) or M2-like (TGF-β, IL-4, IL-10, CCL2, CCL22, CXCL10, Arg1, Chi1, CCR2 and CXCR2) and measured in the brain by qRT-PCR and ELISA. In addition, Western blot and confocal microscopy techniques in conjunction with EOC13.31 cells exposed to similar ethanol-induced oxidative stress and redox conditions were used to determine the underlying mechanism of microglia activation associated with the observed phenotypic changes. ResultsWe show that a single episode of mild to moderate OS in the last trimester of gestation causes GSH depletion, increased protein and lipid peroxidation and inflammatory responses inclined towards a M1-like microglial phenotype (IL-1β, IFN-γ) in fetal brain tissue observed at 6–24 h post exposure. Maternal brain is resistant to many of these marked changes. Using EOC 13.31 cells, we show that GSH homeostasis in microglia is crucial to restore its anti-inflammatory state and modulate inflammation. Microglia under oxidative stress maintain a predominantly M1 activation state. Additionally, GSH depletion prevents the appearance of the M2-like phenotype, while enhancing morphological changes associated with a M1-like phenotype. This observation is also validated by an increased expression of inflammatory signatures (IL-1β, IFN-γ, IL-6, CCL9, CXCR2). In contrast, conserving intracellular GSH concentrations eliminates OS which precludes the nuclear translocation and more importantly the phosphorylation of the NFkB p105 subunit. These cells show significantly more pronounced elongations, ramifications, and the enhanced expression of M2-like microglial phenotype markers (IL-10, IL-4, TGF-β, CXCL10, CCL22, Chi, Arg, and CCR2). Conclusions Taken together, our data show that maintaining GSH homeostasis is not only important for quenching OS in the developing fetal brain, but equally critical to enhance M2 like microglia phenotype, thus suppressing inflammatory responses elicited by environmental stressors.

Tailoring an alcohol intervention for AIAN women of childbearing age: listening to the community

Article

Aug 2017
ALCOHOL CLIN EXP RES

Background: Reduction of risky drinking in women of childbearing age is one strategy that may be employed to prevent fetal alcohol spectrum disorder, a sequela of prenatal alcohol-exposure. Communities differ in risk and protective factors, necessitating culturally informed interventions for maximal efficacy. This manuscript describes the modification of an existing web-based SBIRT intervention to reduce risky drinking among AIAN women of child-bearing age in Southern California into a peer-to-peer based intervention using motivational interviewing. Methods: The modification process was iterative and included various community focus groups, interviews, and a final review. Results: Intervention modification was required for cultural congruence. Components of the peer-to-peer intervention designed by this project included a flip chart used to guide the motivational interviewing, charts of the financial and physical costs of alcohol consumption, revised baseline and follow-up questionnaires, and guidance regarding the application of motivational interviewing techniques. Conclusions: This study may inform the modification of future interventions among AIAN communities. This article is protected by copyright. All rights reserved.

Hair Trace Element and Electrolyte Content in Women with Natural and In Vitro Fertilization-Induced Pregnancy

Article

Full-text available

Jan 2018
BIOL TRACE ELEM RES

The objective of the present study was to perform comparative analysis of hair trace element content in women with natural and in vitro fertilization (IVF)-induced pregnancy. Hair trace element content in 33 women with IVF-induced pregnancy and 99 age- and body mass index-matched control pregnant women (natural pregnancy) was assessed using inductively coupled plasma mass spectrometry. The results demonstrated that IVF-pregnant women are characterized by significantly lower hair levels of Cu, Fe, Si, Zn, Ca, Mg, and Ba at p < 0.05 or lower. Comparison of the individual levels with the national reference values demonstrated higher incidence of Fe and Cu deficiency in IVF-pregnant women in comparison to that of the controls. IVF pregnancy was also associated with higher hair As levels (p < 0.05). Multiple regression analysis revealed a significant interrelation between IVF pregnancy and hair Cu, Fe, Si, and As content. Hair Cu levels were also influenced by vitamin/mineral supplementation and the number of pregnancies, whereas hair Zn content was dependent on prepregnancy anthropometric parameters. In turn, planning of pregnancy had a significant impact on Mg levels in scalp hair. Generally, the obtained data demonstrate an elevated risk of copper, iron, zinc, calcium, and magnesium deficiency and arsenic overload in women with IVF-induced pregnancy. The obtained data indicate the necessity of regular monitoring of micronutrient status in IVF-pregnant women in order to prevent potential deleterious effects of altered mineral homeostasis.

Letter to the Editor: Why do pregnant South African women drink alcohol? A call to action for more qualitative investigations

Article

Full-text available

Dec 2015

Olusanya, O., & Barry, A. (2015). Letter to the Editor: Why do pregnant South African women drink alcohol? A call to action for more qualitative investigations. The International Journal Of Alcohol And Drug Research, 4 (2), 171-174. doi: http://dx.doi.org/10.7895/ijadr.v4i2.213 Even though the adverse effects of alcohol consumption during pregnancy have been well documented, millions of babies each year continue to be affected by fetal alcohol spectrum disorders (FASD). This is concerning given that FASD is completely preventable. FASDs have been documented across a variety of races and geographical regions worldwide, yet the highest known prevalence rates are recorded in Africa. Specifically, for every 1000 children born in the Western Cape Province of South Africa, approximately 59.3 to 91.0 are determined to have fetal alcohol syndrome, the most severe form of FASD. While the risk factors contributing to FASDs have been examined quantitatively among South African women, there is a dearth of qualitative investigations that articulate and contextualize the underling motivations, beliefs, and attitudes that influence these risk factors. Qualitative investigations have been conducted in other geographic regions (e.g., Australia), but are not generalizable to South Africa. Qualitative investigations, which explore the familial, social, cultural, and economic factors that influence maternal drinking, are needed to inform future health promotion programs and interventions aimed at decreasing and ultimately eliminating maternal alcohol consumption among South African women.

Vitamin D Deficiency in Pregnant Ukrainian Women: Effects of Alcohol Consumption on Vitamin D Status

Article

Jan 2017

Objective: Heavy alcohol consumption can alter vitamin D status; however, the relationships between alcohol consumption and vitamin D concentrations in pregnant women have not been well studied. The aim of this study was to investigate the vitamin D status in a population of alcohol-exposed (N = 180) and low/unexposed control (N = 179) Ukrainian pregnant women. Methods: Women who attended prenatal care facilities in 2 regions of Ukraine (Rivne and Khmelnytsky) for a routine prenatal visit were screened for the study. At the time of enrollment (20.4 ± 7.0 weeks of gestation), blood samples and alcohol consumption data (during a typical week around conception and the most recent 2 weeks) were collected. Vitamin D status was assessed by 25-hydroxyvitamin D [25(OH)D] concentrations. Results: A high prevalence of suboptimal vitamin D status in pregnant Ukrainian women was observed. Overall, 50.1% and 33.4% of the women were classified as vitamin D deficient [25(OH)D < 20 ng/mL] or insufficient [25(OH)D ≥ 20 ng/mL and ≤30 ng/mL], respectively, based on 2011 Endocrine Society guidelines. Alcohol-exposed women had significantly lower 25(OH)D concentrations than low/unexposed women in Spring (p = 0.006) and Winter (p = 0.022). When vitamin D concentrations were grouped into sunny season (Summer + Fall) compared to not sunny season (Winter + Spring), there was a significant ethanol by season interaction (p = 0.0028), with alcohol-drinking women having lower circulating vitamin D compared to low/unexposed women in seasons of low sun availability. Conclusions: These data suggest that when vitamin D concentrations are generally low (e.g., during seasons of low sun availability), alcohol consumption during pregnancy has a negative impact on vitamin D status.

Genetically programmed retinoic acid deficiency during gastrulation phenocopies most known developmental defects due to acute prenatal alcohol exposure in FASD

Article

Full-text available

Jun 2023

Fetal Alcohol Spectrum Disorder (FASD) arises from maternal consumption of alcohol during pregnancy affecting 2%-5% of the Western population. In Xenopus laevis studies, we showed that alcohol exposure during early gastrulation reduces retinoic acid (RA) levels at this critical embryonic stage inducing craniofacial malformations associated with Fetal Alcohol Syndrome. A genetic mouse model that induces a transient RA deficiency in the node during gastrulation is described. These mice recapitulate the phenotypes characteristic of prenatal alcohol exposure (PAE) suggesting a molecular etiology for the craniofacial malformations seen in children with FASD. Gsc +/Cyp26A1 mouse embryos have a reduced RA domain and expression in the developing frontonasal prominence region and delayed HoxA1 and HoxB1 expression at E8.5. These embryos also show aberrant neurofilament expression during cranial nerve formation at E10.5 and have significant FASD sentinel-like craniofacial phenotypes at E18.5. Gsc +/Cyp26A1 mice develop severe maxillary malocclusions in adulthood. Phenocopying the PAE-induced developmental malformations with a genetic model inducing RA deficiency during early gastrulation strongly supports the alcohol/vitamin A competition model as a major molecular etiology for the neurodevelopmental defects and craniofacial malformations seen in children with FASD.

Prenatal alcohol exposure risk perception dimensions and influencing factors: A systematic review and conceptual model

Article

Apr 2023
AUST NZ J PUBL HEAL

Objective: This paper aims to explore the available literature to understand how risks regarding prenatal alcohol exposure are perceived. Methods: A systematic review (PROSPERO; CRD 42020212887) was undertaken. PubMed, Embase, PsycINFO, and CINAHL were searched for relevant quantitative and qualitative studies. A thematic analysis of the studies was performed. Results: Fifteen articles-nine quantitative and six qualitative studies met the inclusion criteria. Three dimensions of risk perceptions were identified-perceived susceptibility, perceived severity, and affective risk perception. Three influencing factors of these dimensions were also identified: information (i.e., consistency, confirmation bias, strength of the evidence, and perceived relevance), sociocultural (i.e., social inclusivity, cultural context, and risk interpretation), and individual (i.e., risks versus benefits, controllability, and experience). These dimensions and influencing factors were brought together to create the proposed novel Pregnancy Alcohol Risk Perception (PARP) conceptual model. Conclusions: The novel PARP conceptual model developed from the current literature provides a framework to guide understanding of risk perceptions, which includes a wide range of potential influencing factors. Implications for public health: The novel PARP conceptual model provides the groundwork for further refinement with stakeholders, which could in turn be used to inform the design of interventions and health promotional materials to support harm reduction approaches and prevention of prenatal alcohol exposure.

Behavioral and Mental Health Disorders (Including Attentional Disorders)

Chapter

Feb 2023

The focus of this chapter is on behavioral and mental health disorders (BMHDs). The disorders represent an amalgamation of challenging behaviors, emotional and behavioral consequence of brain dysfunction associated with medical and neurological disorders, and equally complex, primary psychiatric disorders. The emphasis is on autism spectrum disorders (ASD), attention-deficit hyperactivity disorder (ADHD), cerebral palsy (CP), and fetal alcohol spectrum disorder (FASD). As discrete entities, there are many differences between their underlying pathophysiology and phenotypic expression. Genome-wide association scans suggest some shared predisposition and sensitivities to negative environmental and psychosocial experiences. These concepts are elaborations of the biopsychosocial model. This model rests on the multi-direction interrelationships between life experiences (psychosocial forces) such as temperament, attachment and adverse experiences, and the complex of predisposing factors noted above. The primary challenge for the authors is dealing with the breadth of this subject. There are dozens of behavioral and psychiatric disorders to consider. Narrowing the focus to those listed above requires condensing the explosive growth of new information from genetics, epigenetics, translational neurosciences, neurophysiology, and functional neuroimaging of pediatric neurodevelopmental disorders into a single chapter. Two issues dominate (1) the transactional nature of gene environment interactions on emerging phenotypes, and (2) the growing realization that many of these phenotypes represent spectrum disorders that suggest final common pathways. From a biopsychosocial perspective, the neurodevelopmental disorders reviewed in this chapter differ in terms of pathophysiology, but are not mutually exclusive disorders. For example, ADHD is common in children with CP, FAS, and ASD. This realization reinforces the idea that many neurodevelopmental/psychiatric disorders are not discrete entities with firm boundaries. They are in fact products of many biological and psychosocial influences. From a behavioral health perspective, the negative consequences of adverse childhood experiences on these disorders are not a linear or deterministic process. Resilience and other protective factors and timely interventions can attenuate or prevent some of the negative outcomes discussed in this chapter.

Overview of FASD: How Our Understanding of FASD Has Progressed

Chapter

Aug 2021

Alan D. Price

Some historical clues suggest an ancient understanding that alcohol should be avoided during pregnancy, but these may have been overstated. Further evidence appears during times of widespread alcohol use in the middle ages, but the current understanding of prenatal alcohol exposure and FASD has its source in the latter half of the 20th century. This chapter describes the history of FASD, from Aristotle and the Old Testament up to modern neuroscience and genetics. After bringing the reader back to the present day, there follows a review of the mechanisms of alcohol-related harm to the foetus, and factors that mediate that harm.

New Approaches to Diagnosis: the Role of Neurobehavioral Disorder associated with Prenatal Alcohol Exposure (ND-PAE)

Chapter

Aug 2021

Julie A Kable

Neurobehavioral disorder associated with prenatal alcohol exposure (ND_PAE) was proposed to capture the full range of mental health problems found in individuals who have been adversely impacted by their prenatal alcohol exposure (PAE). The disorder can be used with individuals who both have and do not have the physical symptoms of PAE. Specific symptoms of the disorder are described and the psychometric characteristics of the disorder are reviewed. Although there is substantial evidence to support the validity of the symptoms in individuals with a history of PAE, the unique formulation of these symptoms as currently proposed in the American Psychiatric Diagnostic and Statistical Manual, fifth edition (DSM-5), may need modification.

Folic acid prevents functional and structural heart defects induced by prenatal ethanol exposure

Article

Jan 2021

Increased regurgitant blood flow has been linked to endocardial cushion defects and resultant congenital heart diseases (CHDs). Prenatal alcohol exposure (PAE) has been shown to alter early blood flow resulting in abnormal endocardial cushions and CHDs. Compounds, including folic acid (FA), mitigate PAE effects and prevent CHDs, but few studies have assessed their effects on blood flow. We modeled binge drinking in quail embryos at gastrulation. Embryos were exposed to ethanol alone, FA (3.2 μg/egg) alone, and the two simultaneously. We quantified in cardiac looping stages (equivalent to 4 weeks of human gestation) regurgitant blood flow with Doppler optical coherence tomography (OCT) and endocardial cushion volumes using OCT imaging. Incidences of abnormal body curvature and heart rates were also measured. Embryos exposed to ethanol showed significantly increased regurgitant blood flow compared to controls, while embryos given FA with ethanol had significantly reduced regurgitant blood flow but did not return to control levels. Ethanol exposure led to significantly smaller, abnormal endocardial cushions and the addition of FA improved their size, but they remained smaller than controls. Abnormal body curvatures after PAE were reduced in incidence but not fully prevented by FA. FA supplementation partially alleviated PAE induced abnormal cardiovascular function and morphology. Normal blood flow and endocardial cushions are both required to produce a healthy four-chambered heart. These findings support that FA supplementation should begin early in pregnancy to prevent heart as well as neural tube defects. Investigations into the efficacy of combinations of compounds to prevent PAE-induced defects is warranted.

Minerals in pregnancy and newborns

Chapter

Jan 2021

Pregnant women are at risk of developing trace elements deficiency. This is attributed to deficient dietary sources, physiological changes during pregnancy, and genetic factors. Adequate trace elements are essential for the health of the mother and her fetus. Many deleterious effects are associated with trace elements deficiency, which can be extended even after delivery and contribute to maternal and fetal morbidity and mortality. Trace elements deficiency can lead to congenital malformations, e.g., neural tube defects, aortic aneurysm, and valvular lesions. Clinical trials demonstrated that supplementation of trace elements has beneficial effects. This chapter highlights the molecular mechanism by which select trace elements are implicated in the pathogenicity of selected clinical conditions such as gestational diabetes, preeclampsia, low birth weight, and teratogenicity.

Epidemiology of prenatal alcohol use and fetal alcohol spectrum disorders

Thesis

Full-text available

Apr 2018

Cheryl McQuire

Chornobyl Radiation ‐ Congenital Anomalies ‐ A Persisting Dilemma

Article

Jul 2020

Wladimir Wertelecki

Compute population prevalence rates of neural tube defects and microcephaly as well as levels of incorporated Cs137 by pregnant women in two areas of the Rivne Province of Ukraine, a northern half (Polissia) polluted by Chornobyl radiation and not‐Polissia areas. Monitoring of congenital malformations was conducted with adherence to methods adopted by a European surveillance network (EUROCAT). Incorporated Cs137 (Bq/kg) by pregnant women residing in the Polissia and not‐Polissia areas were obtained concurrently with prenatal ultrasound examinations. In Polissia, the incorporated Cs137 levels by pregnant women as well as the prevalence rates of neural tube defects and microcephaly are significantly higher than in not‐Polissia. In Polissia, the prevalence rates of neural tube defects and microcephaly are among the highest in Europe. The debate concerning the teratogenic impact of chronic exposures to low levels of ionizing radiation was re‐ignited by our 2010 report. Health agencies uphold the notion that exposure to Chornobyl radiation levels are too low to be teratogenic, which is inconsistent with our observations. Further investigations in Rivne by international teams can, we believe, contribute facts to the ongoing debate. Our monitoring system, experience and data can facilitate concurrent investigations of teratogenic risks from exposures to other sources of ionizing radiation, alcohol, folate and zinc deficiencies, among other risk factors. Study of genomic impacts can likewise be undertaken. This article is protected by copyright. All rights reserved.

Diet quality, nutrient intakes and biochemical status of New Zealand women of childbearing age according to alcohol consumption patterns

Article

Feb 2020

Objective To investigate associations between alcohol consumption patterns and diet quality, nutrient intakes and biochemical profile of women of childbearing age. Design Nutrient intake data from 24 h diet recalls, alcohol consumption data and diet quality from the Dietary Habits Questionnaire, and biochemical analyses from the cross-sectional 2008/09 Adult Nutrition Survey in New Zealand. Setting New Zealand households. Participants New Zealand women aged 18–45 years ( n 1124). Results All analyses were completed using Stata and survey weights were used to allow for the complex survey design to produce population estimates. Multinomial logistic regression models were used to examine the associations between drinking patterns and the variables of interest, with ‘infrequent moderate/light’ drinkers being the reference category. The findings indicate that alcohol-consuming women of childbearing age tend to replace food energy with alcohol energy ( P = 0·022). ‘More frequent heavy’ and ‘more frequent moderate/light’ drinkers had higher intakes of total, mono- and polyunsaturated fats with the latter group also consuming higher levels of saturated fats ( P < 0·05). Women who were ‘infrequent moderate/light’ drinkers had relatively better diet quality, nutrient intakes and adequate biochemical status in comparison to other drinkers and abstainers. ‘Infrequent heavy’ drinkers, who were predominantly younger in age, had lower serum vitamin B 12 levels ( P = 0·01) with a higher proportion of women in this category having below-recommended levels of serum folate ( P < 0·05). Conclusions Alcohol consumption, especially heavy drinking patterns, may compromise nutritional status of women of childbearing age.

Review: The Role of Zinc Signaling in Reproduction

Chapter

Dec 2019

Human infertility has become a serious medical and social issue worldwide, especially in developed countries. Numerous assisted reproductive technologies (ARTs) (e.g., artificial insemination [AI], in vitro fertilization [IVF], and intracytoplasmic sperm injection [ICSI]) are widely used to treat infertility, but when embryos produced using these techniques are transferred, the pregnancy outcome is only approx. 20–50%, necessitating further improvement in ARTs. Many factors (including zinc) affect successful fertilization, further embryonic development, and the establishment and maintenance of pregnancy. Zinc signaling has many physiological functions in various types of cells, and it is thus speculated that zinc signaling has an important role in the abovementioned reproductive events, even in germ cells and reproductive tissues. Prior studies demonstrated that zinc deficiency results in a number of anomalies in the formation and maturation of spermatozoa, ovulation, and fertilization. During pregnancy, zinc deficiency causes spontaneous abortion, pregnancy-related toxemia, extended pregnancy or preterm birth, malformations, and retarded growth. The molecular mechanisms underlying zinc signaling in reproduction are not yet clear. In this chapter, we summarize the current knowledge about zinc signaling in reproduction—mainly in mammals—and we discuss recent advances in this field.

Fetal Alcohol Spectrum Disorders: A Review of the Neurobehavioral Deficits Associated With Prenatal Alcohol Exposure

Article

Apr 2019

In utero alcohol exposure can disrupt the development of the fetal brain and result in a wide‐range of neurobehavioral outcomes collectively known as fetal alcohol spectrum disorders (FASD). This paper provides a comprehensive review of the cognitive and behavioral outcomes of prenatal alcohol exposure, including domains of general intelligence, executive functioning, language development, learning and memory, adaptive functioning, academic performance, and concurrent psychopathology. In addition, the current status of the neurobehavioral profile of FASD and its potential as a diagnostic tool will be discussed. This article is protected by copyright. All rights reserved.

Role of zinc insufficiency in fetal alveolar macrophage dysfunction and RSV exacerbation associated with fetal ethanol exposure

Article

Dec 2018
ALCOHOL

Background: We previously reported that maternal alcohol use significantly increases the risk of sepsis in premature and term newborns. In the mouse, fetal ethanol exposure results in an immunosuppressed phenotype for the alveolar macrophage (AM) and decreases bacterial phagocytosis. In pregnant mice, ethanol decreased AM zinc homeostasis, which contributed to immunosuppression and impaired AM phagocytosis. In this study, we explored whether ethanol-induced zinc insufficiency extended to the pup AMs and contributed to immunosuppression and exacerbated viral lung infections. Methods: C57BL/6 female mice were fed a liquid diet with 25% ethanol-derived calories or pair-fed a control diet with 25% of calories as maltose-dextrin. Some pup AMs were treated in vitro with zinc acetate before measuring zinc pools or transporter expression and bacteria phagocytosis. Some dams were fed additional zinc supplements in the ethanol or control diets, and then we assessed pup AM zinc pools, zinc transporters, and the immunosuppressant TGFβ1. On postnatal day 10, some pups were given intranasal saline or respiratory syncytial virus (RSV), and then AM RSV phagocytosis and the RSV burden in the airway lining fluid were assessed. Results: Fetal ethanol exposure decreased pup AM zinc pools, zinc transporter expression, and bacterial clearance, but in vitro zinc treatments reversed these alterations. In addition, the expected ethanol-induced increase in TGFβ1 and immunosuppression were associated with decreased RSV phagocytosis and exacerbated RSV infections. However, additional maternal zinc supplements blocked the ethanol-induced perturbations in the pup AM zinc homeostasis and TGFβ1 immunosuppression, thereby improving RSV phagocytosis and attenuating the RSV burden in the lung. Conclusion: These studies suggest that, despite normal maternal dietary zinc intake, in utero alcohol exposure results in zinc insufficiency, which contributes to compromised neonatal AM immune functions, thereby increasing the risk of bacterial and viral infections.

The Effects of Alcohol and Drugs of Abuse on Maternal Nutritional Profile During Pregnancy

Preprint

Full-text available

Jun 2018

The consumption of alcohol and drugs of abuse among pregnant women has experienced a significant increase in the last decades. Optimal maternal nutritional status is of great importance for proper fetal development, yet is often altered with alcohol or drugs consumption. There is a lack of information on the effects of alcohol and drugs on maternal nutritional status, so the focus of this review was to provide an overview on nutrional status of mother and fetus in abusers pregnant women. Alcohol and drugs consumption can adversely affect the quality and quantity of proper nutrient supply and energy intake, resulting in malnutrition especially of micronutrients (vitamins, omega-3, folic acid, zinc, choline, iron, copper, selenium). When maternal nutritional status is compromised by alcohol and drugs essential nutrients are not available for the fetus, this can result in suboptimal outcomes like Intrauterine Growth Restriction (IUGR) or Fetal Alcohol Spectrum Disorder (FASD). It is critical to determine a means to resolve and reduce the physical and neurological malformations that develop in the fetus as a result of prenatal alcohol and drugs exposure combined with poor maternal nutrition. Prenatal nutrition interventions are required that may prevent or alleviate the development of such abnormalities.

Effects of Prenatal Alcohol Exposure (PAE): Insights into FASD using PAE Mouse Models

Article

Jan 2018

The potential impact of prenatal alcohol exposure (PAE) varies considerably among exposed individuals, with some displaying serious alcohol-related effects and others showing few or even no overt signs of a fetal alcohol spectrum disorder (FASD). In animal models variables such as nutrition, genetic background, health, other drugs, and stress, as well as dosage, duration and gestational timing of alcohol exposure can all be controlled in a way not possible in a clinical situation. In this review we examine mouse PAE models and focus on those with demonstrated craniofacial malformations, abnormal brain development, or behavioural phenotypes that may be considered FASD-like outcomes. Analysis of these data should provide a valuable tool for researchers wishing to choose the PAE model best-suited to their research questions or to investigate established PAE models for FASD comorbidities. It should also allow recognition of patterns linking gestational timing, dosage and duration of PAE with FASD-like outcomes. The latter could be particularly insightful and lead to a better understanding of the molecular mechanisms underlying FASD.

Zinc deficiency as a mediator of toxic effects of alcohol abuse

Article

Full-text available

Oct 2018
EUR J NUTR

Objective: To review data on the role of ethanol-induced alteration of Zn homeostasis in mediation of adverse effects of alcohol abuse. Methods: The scholarly published articles on the association between Zn metabolism and alcohol-associated disorders (liver, brain, lung, gut dysfunction, and fetal alcohol syndrome) have been reviewed. Results: It is demonstrated that alcohol-induced modulation of zinc transporters results in decreased Zn levels in lungs, liver, gut, and brain. Zn deficiency in the gut results in increased gut permeability, ultimately leading to endotoxemia and systemic inflammation. Similarly, Zn deficiency in lung epithelia and alveolar macrophages decreases lung barrier function resulting in respiratory distress syndrome. In turn, increased endotoxemia significantly contributes to proinflammatory state in alcoholic liver disease. Finally, impaired gut and liver functions may play a significant role in alcoholic brain damage, being associated with both increased proinflammatory signaling and accumulation of neurotoxic metabolites. It is also hypothesized that ethanol-induced Zn deficiency may interfere with neurotransmission. Similar changes may take place in the fetus as a result of impaired placental zinc transfer, maternal zinc deficiency, or maternal Zn sequestration, resulting in fetal alcoholic syndrome. Therefore, alcoholic Zn deficiency not only mediates the adverse effects of ethanol exposure, but also provides an additional link between different alcohol-induced disorders. Conclusions: Generally, current findings suggest that assessment of Zn status could be used as a diagnostic marker of metabolic disturbances in alcohol abuse, whereas modulation of Zn metabolism may be a potential tool in the treatment of alcohol-associated disorders.

Dietary Patterns and Alcohol Consumption During Pregnancy: Secondary Analysis of Avon Longitudinal Study of Parents and Children

Article

Full-text available

Apr 2017

Background: Large general population surveys show that heavy regular and episodic alcohol consumption are associated with lower intakes of fruits and vegetables, and higher intakes of processed and fried meat. This is of particular concern regarding pregnant women, as both alcohol intake and inadequate maternal nutrition are independently associated with adverse fetal outcomes. The current study aimed to determine associations between maternal dietary patterns and alcohol consumption during pregnancy. Methods: Women were participating in the Avon Longitudinal Study of Parents and Children, and provided details of alcohol consumption at 18 weeks' gestation and diet at 32 weeks' gestation (n = 9,839). Dietary patterns were derived from the food frequency questionnaire data using principal components analysis. Associations between alcohol consumption and dietary patterns were determined using multiple linear regression, adjusted for various sociodemographic and lifestyle factors. Results: After adjustment, drinking ≥1 unit/d during the first trimester (β = 0.23 [95% CI: 0.08, 0.38]; p = 0.002) and binge drinking (≥4 units in 1 day) during the first half of pregnancy (β = 0.14 [95% CI: 0.07, 0.21]; p < 0.0001) were associated with greater adherence to the "Processed" dietary pattern (high intakes of processed meat and low intakes of fruit and vegetables). Light-to-moderate alcohol consumption (≤1 drink/d) during the first trimester was associated with greater adherence to the "Health conscious" dietary pattern (high intakes of fruit, vegetables, whole grains, and fish) (β = 0.09 [95% CI: 0.04, 0.14]; p < 0.0001). Conclusions: Two important components of health behavior during pregnancy appear to be related: greater consumption of processed foods associated with heavier alcohol consumption, and healthier dietary choices associated with light-to-moderate alcohol intake. Potential synergistic effects of these behaviors may have implications for maternal and fetal health and warrant further investigation. A more holistic approach to addressing health behaviors in women of reproductive age is required.

Dietary Zinc Supplementation and Prenatal Ethanol Exposure

Chapter

Jul 2013

Exposure to alcohol during pregnancy is associated with an increased risk of spontaneous abortion, growth retardation, congenital malformations and central nervous system dysfunction [1, 2]. These negative birth outcomes, which are collectively referred to as fetal alcohol spectrum disorder (FASD), range in severity from full fetal alcohol syndrome (FAS) through milder although clinically significant forms which can affect physical and behavioural outcomes (i.e. alcohol-related birth defects (ARBD) and alcohol-related neurodevelopmental disorders (ARND)). These outcomes are associated not only with chronic consumption of alcohol at high intakes and frequency but also with a single episode of alcohol intake, which is commonly called ‘binge drinking’ (>4 drinks/occasion). Although abstinence from alcohol during pregnancy would prevent these disorders, the motivation for self-restraint from drinking alcohol is not uniformly accepted among women [3–6]. Moreover, up to two-thirds of pregnancies are reported to be unplanned, indicating that many women may be unaware of their pregnancy when consuming alcohol [3, 5, 6]. Thus, the consumption of alcohol during pregnancy will continue to negatively impact on birth outcomes well into the future.

Maternal Nutritional Status and the Risk for Orofacial Cleft Offspring in Humans

Article

Full-text available

Nov 2004

Periconceptional folate and folic acid intake prevents orofacial clefts (OFC) in the offspring. It has been suggested that other nutrients also play a role. We investigated the preconceptional intake of macronutrients (protein, fat, carbohydrate, fiber, and cholesterol), vitamins (vitamin A, retinol, beta-carotene, ascorbic acid, and alpha-tocopherol), minerals (calcium, phosphorus, iron, magnesium, and zinc) and food groups in mothers of OFC children and controls. At approximately 14 mo after the index pregnancy, 206 mothers of a child with a nonsyndromic OFC and 203 control mothers completed a FFQ on current food intake and a general questionnaire. After exclusion of pregnant and lactating mothers, mothers who reported a change in diet compared with the preconceptional period, and those for whom periconceptional folic acid supplement use was unclear, 182 OFC mothers and 173 control mothers were evaluated. Macronutrient, vitamin, mineral, and food group intakes were compared. After adjustment for energy, quintiles of dietary nutrient intake and odds ratios with 95% CI were calculated. The preconceptional intake of all macronutrients, vitamins, minerals, and food groups with the exception of milk (products), potatoes, pies/cookies were lower in OFC mothers than in controls. The energy-adjusted intakes of vegetable protein, fiber, beta-carotene, ascorbic acid, alpha-tocopherol, iron, and magnesium were significantly lower in cases compared with controls. Increasing intakes of vegetable protein, fiber, ascorbic acid, iron, and magnesium decreased OFC risk. In conclusion, a higher preconceptional intake of nutrients predominantly present in fruits and vegetables reduces the risk of offspring affected by OFC.

The influence of gestational zinc deficiency on the fetal insulin-like growth factor axis in the rat

Article

Full-text available

Feb 2010
EXP BIOL MED

The insulin-like growth factor (IGF) axis, a key regulator of embryonic growth and development, is exquisitely sensitive to the nutrient status of the animal. In addition to macronutrient deficiencies, zinc deficiency can impact the IGF axis. Gestational zinc deficiency is teratogenic, resulting in intrauterine growth retardation and structural abnormalities. The aim of this study was to investigate the effects of gestational zinc deficiency on the fetal IGF axis in a rat model. From gestation day (GD) 0.5, dams consumed zinc-deficient (ZD, 0.3 mg zinc/kg) or control (25 mg zinc/kg) diet ad libitum, while a third group of dams consumed the control diet in amounts equivalent to the food intake of the ZD dams (Paired group). On GD 19.5 fetal tissue, blood and amniotic fluid were collected. Fetal growth was significantly reduced by zinc deficiency compared with the Paired and Control groups. Fetuses from the Paired group were smaller compared with the Control, but only ZD fetuses had structural malformations. Amniotic fluid IGF-1 concentrations were significantly lower in the Paired group than in the ZD and Control groups. Plasma of ZD fetuses contained lower levels of IGF binding protein-1 when compared with fetuses in the Paired and Control groups. Fetal liver IGF-1 mRNA levels were lower in the ZD fetuses than in the Paired and Control fetuses. These observations suggest that differences in the fetal IGF axis between ZD and Paired groups contribute to the poor pregnancy outcome and enhanced fetal growth retardation observed with zinc deficiency.

Maternal Micronutrient Deficiency, Fetal Development, and the Risk of Chronic Disease

Article

Full-text available

Mar 2010
J NUTR

Early life nutritional exposures, combined with changes in lifestyle in adult life, can result in increased risk of chronic diseases. Although much of the focus on the developmental origins of disease has been on birth size and growth in postnatal life and the availability of energy and protein during these critical developmental periods, micronutrient deficiencies may also play an important role in fetal growth and development. Micronutrient status in fetal and early life may alter metabolism, vasculature, and organ growth and function, leading to increased risk of cardiometabolic disorders, adiposity, altered kidney function, and, ultimately, to type 2 diabetes and cardiovascular diseases. This review elucidates pathways through which micronutrient deficiencies lead to developmental impairment and describes the research to date on the evidence that micronutrient deficiencies in utero influence the development of chronic disease risk. Animal studies, observational human studies examining maternal diet or micronutrient status, and limited data from intervention studies are reviewed. Where data are lacking, plausible mechanisms and pathways of action have been derived from the existing animal and in vitro models. This review fills a critical gap in the literature related to the seminal role of micronutrients in early life and extends the discussion on the developmental origins of health and disease beyond birth size and energy and protein deficiency.

Effect of Prenatal Zinc Supplementation on Birthweight

Article

Full-text available

Oct 2009

Although iron and zinc deficiencies are known to occur together and also appear to be high in Ghana, a few supplementation studies addressed this concurrently in pregnancy. In a double-blind, randomized controlled trial, 600 pregnant women in Ghana were randomly assigned to receive either a combined supplement of 40 mg of zinc as zinc gluconate and 40 mg of iron as ferrous sulphate or 40 mg of elemental iron as ferrous sulphate. Overall, there was no detectable difference in the mean birthweight between the study groups, although the effect of iron-zinc supplementation on the mean birthweight was masked by a strong interaction between the type of supplement and the iron status of participants [F (1,179) = 5.614, p = 0.019]. Prenatal iron-zinc supplementation was effective in increasing the mean birthweight among anaemic and iron-deficient women but not among women with elevated iron stores in early pregnancy.

The Role of Zinc in the Modulation of Neuronal Proliferation and Apoptosis

Article

Full-text available

Sep 2009
NEUROTOX RES

Although a requirement of zinc (Zn) for normal brain development is well documented, the extent to which Zn can modulate neuronal proliferation and apoptosis is not clear. Thus, we investigated the role of Zn in the regulation of these two critical events. A low Zn availability leads to decreased cell viability in human neuroblastoma IMR-32 cells and primary cultures of rat cortical neurons. This occurs in part as a consequence of decreased cell proliferation and increased apoptotic cell death. In IMR-32 cells, Zn deficiency led to the inhibition of cell proliferation through the arrest of the cell cycle at the G0/G1 phase. Zn deficiency induced apoptosis in both proliferating and quiescent neuronal cells via the intrinsic apoptotic pathway. Reductions in cellular Zn triggered a translocation of the pro-apoptotic protein Bad to the mitochondria, cytochrome c release, and caspase-3 activation. Apoptosis is the resultant of the inhibition of the prosurvival extracellular-signal-regulated kinase, the inhibition of nuclear factor-kappa B, and associated decreased expression of antiapoptotic proteins, and to a direct activation of caspase-3. A deficit of Zn during critical developmental periods can have persistent effects on brain function secondary to a deregulation of neuronal proliferation and apoptosis.

Developmental Origins of Health and Disease: Brief History of the Approach and Current Focus on Epigenetic Mechanisms

Article

Full-text available

Oct 2009
SEMIN REPROD MED

"Barker's hypothesis" emerged almost 25 years ago from epidemiological studies of birth and death records that revealed a high geographic correlation between rates of infant mortality and certain classes of later adult deaths as well as an association between birthweight and rates of adult death from ischemic heart disease. These observations led to a theory that undernutrition during gestation was an important early origin of adult cardiac and metabolic disorders due to fetal programming that permanently shaped the body's structure, function, and metabolism and contributed to adult disease. This theory stimulated interest in the fetal origins of adult disorders, which expanded and coalesced approximately 5 years ago with the formation of an international society for developmental origins of health and disease (DOHaD). Here we review a few examples of the many emergent themes of the DOHaD approach, including theoretical advances related to predictive adaptive responses of the fetus to a broad range of environmental cues, empirical observations of effects of overnutrition and stress during pregnancy on outcomes in childhood and adulthood, and potential epigenetic mechanisms that may underlie these observations and theory. Next, we discuss the relevance of the DOHaD approach to reproductive medicine. Finally, we consider the next steps that might be taken to apply, evaluate, and extend the DOHaD approach.

Diet and deprivation in pregnancy

Article

Full-text available

Sep 2009
BRIT J NUTR

Deprivation is associated with poor pregnancy outcome but the role of nutrition as a mediating factor is not well understood. We carried out a prospective cohort study of 1461 singleton pregnancies in Aberdeen, UK during 2000-6. We measured nutrient intake and supplement use, B vitamin and homocysteine status, birth weight, gestational age, neonatal treatment and socio-economic deprivation status. Women in the most deprived deciles were approximately 6 years younger and half as likely to take folic acid supplements periconceptually as the least deprived mothers. Deprivation was associated with low blood folate, high homocysteine and diets low in protein, fibre and many of the vitamins and minerals. The diets of the more deprived women were also characterised by low intakes of fruit, vegetables and oily fish and higher intakes of processed meat, fried potatoes, crisps and snacks. Deprivation was related to preterm birth (OR 1.14 (95 % CI 1.03, 1.25); P = 0.009) and whether the baby required neonatal treatment (OR 1.07 (95 % CI 1.01, 1.14); P = 0.028). Low birth weight was more common in women consuming diets low in vitamin C (OR 0.79 (95 % CI 0.64, 0.97); P = 0.028), riboflavin (OR 0.77 (95 % CI 0.63, 0.93); P = 0.008), pantothenic acid (OR 0.79 (95 % CI 0.65, 0.97); P = 0.023) and sugars (OR 0.78 (95 % CI 0.64, 0.96); P = 0.017) even after adjustment for deprivation index, smoking, marital status and parity. Deprivation in pregnancy is associated with diets poor in specific nutrients and poor diet appears to contribute to inequalities in pregnancy outcome. Improving the nutrient intake of disadvantaged women of childbearing age may potentially improve pregnancy outcome.

Effects of zinc supplementation during pregnancy on pregnancy outcome in women with history of preterm delivery: A double-blind randomized, placebo-controlled trial

Article

Full-text available

Jul 2009
J MATERN-FETAL NEO M

The aim of this study was to assess the effect of high dose zinc (Zn) supplement during pregnancy in pregnancy outcome in healthy pregnant women with a previous preterm delivery in Isfahan, Iran. A double-blind placebo-controlled randomized clinical trial was conducted between January 2007 and June 2008. Eighty-four pregnant women with a previous preterm delivery age 19 to 35 years were randomly allocated to receive either 50 mg/day Zn as Zn sulfate or placebo from 12 to 16 weeks of gestation till delivery. Pregnancy outcome was assessed in term of incidence of intrauterine growth retardation (IUGR), birth weight, crown-heel length, head circumference, Apgar score, and gestational age at delivery. The mean birth head circumference was higher in Zn supplemented group than in the placebo group (35.0 cm vs. 33.7 cm, P < 0.05). Although gestational age at delivery (37.1 week vs. 36.7 week) and birth weight (2960.6 g vs. 2819.0 g) of babies born in Zn supplemented group was slightly higher than placebo group, it was not statistically significant. No significant differences were seen for infant length, Apgar score, and IUGR. Adding Zn supplementation during pregnancy to routine care of women with a previous preterm delivery had no significant effect on the gestational age at delivery and birth weight but increased the birth head circumference.

Maternal serum zinc deficiency in cases of neural tube defect in Gorgan, north Islamic Republic of Iran

Article

Full-text available

Mar 2009

Previous studies have shown a high rate of neural tube defects (NTD) in Gorgan, northern (tub efcs (NTD) in Gorgan, northern Islamic Republic of Iran. This case-control study during 2003-04 compared serum zinc levels and other variables in 23 mothers of neonates affected with NTD and 36 mothers with normal healthy neonates in Dezyani hospital in Gorgan. Mean serum zinc levels in the case and control groups were 13.43 micromol/L (SD 6.3) and 11.41 micromol/L (SD 6.3) respectively. Zinc deficiency was found in 13 (36.5%) of the cases and 7 (19.4%) of the controls. Logistic regression analysis showed an association between the presence of NTD and zinc deficiency (OR 5.06; 95% CI: 1.51-16.94).

Recent Advances in Knowledge of Zinc Nutrition and Human Health

Article

Full-text available

Apr 2009

Zinc deficiency increases the risk and severity of a variety of infections, restricts physical growth, and affects specific outcomes of pregnancy. Global recognition of the importance of zinc nutrition in public health has expanded dramatically in recent years, and more experience has accumulated on the design and implementation of zinc intervention programs. Therefore, the Steering Committee of the International Zinc Nutrition Consultative Group (IZiNCG) completed a second IZiNCG technical document that reexamines the latest information on the intervention strategies that have been developed to enhance zinc nutrition and control zinc deficiency. In particular, the document reviews the current evidence regarding preventive zinc supplementation and the role of zinc as adjunctive therapy for selected infections, zinc fortification, and dietary diversification or modification strategies, including the promotion and protection of breastfeeding and biofortification. The purposes of this introductory paper are to summarize new guidelines on the assessment of population zinc status, as recommended by the World Health Organization (WHO), the United Nations Children's Fund (UNICEF), the International Atomic Energy Agency (IAEA), and IZiNCG, and to provide an overview on several new advances in zinc metabolism. The following papers will then review the intervention strategies individually.

A prospective study of micronutrient status in adolescent pregnancy

Article

Full-text available

Feb 2009
AM J CLIN NUTR

Adolescents are more likely than adults to consume energy-dense, micronutrient-poor diets and to experience adverse pregnancy outcomes. The objectives were to assess micronutrient intake and blood biomarkers prospectively in pregnant adolescents recruited to the About Teenage Eating (ATE) Study and to determine associations with pregnancy outcome. Pregnant adolescents (n = 500) were recruited from 2 UK inner city populations. Dietary intake was assessed with three 24-h dietary recalls, and micronutrient status was assessed by measurement of third trimester blood biomarkers. Pregnancy outcomes included small-for-gestational age (SGA) birth and preterm delivery. Median iron and folate intakes were lower than UK and US recommended amounts. Folate and vitamin B-12 status were lower in smokers, despite no differences in dietary intake. Serum folate was <7.0 nmol/L in 12% of subjects, and serum total homocysteine (tHcy) was elevated (>10 micromol/L) in 20% of subjects. Fifty-two percent of the subjects had iron deficiency anemia, and 30% had serum 25-hydroxyvitamin D concentrations <25 nmol/L. The incidence of SGA birth was higher in subjects with poorer folate status (red blood cell folate, P = 0.003; serum folate, P = 0.02; tHcy, P = 0.01; simple regression) and those with low folate intakes, regardless of the inclusion (P = 0.021) or exclusion (P = 0.049) of intake from supplements (simple regression). Adjustment for confounding variables confirmed the independence of these associations. The risk of SGA birth was also higher in subjects with low food iron intake (P = 0.049), but not when intake included iron from supplements (P = 0.21). The risk of SGA birth was lower in subjects with iron deficiency anemia (P = 0.002). Poor micronutrient intake and status increase the risk of SGA births in pregnant adolescents.

Zinc Deficiency Mediates Alcohol-Induced Alveolar Epithelial and Macrophage Dysfunction in Rats

Article

Full-text available

Aug 2009
AM J RESP CELL MOL

Chronic alcohol abuse impairs both alveolar epithelial and macrophage function, and renders individuals susceptible to acute lung injury, pneumonia, and other serious lung diseases. Zinc deficiency, which is known to impact both epithelial and immune cell functions, is also associated with alcohol abuse. In this study, chronic alcohol ingestion (6 wk) in rats altered expression of key zinc transporters and storage proteins in the small intestine and the lung, and decreased zinc levels in the alveolar compartment. Zinc supplementation of alveolar epithelial monolayers derived from alcohol-fed rats in vitro, or of the diets of alcohol-fed rats in vivo, restored alveolar epithelial barrier function, and these improvements were associated with salutary changes in tight junction protein expression and membrane localization. In parallel, dietary zinc supplementation increased intracellular zinc levels, GM-CSF receptor expression, and bacterial phagocytic capacity in the alveolar macrophages of alcohol-fed rats. Together, these studies implicate zinc deficiency as a novel mechanism mediating alcohol-induced alveolar epithelial and macrophage dysfunction. Importantly, these findings argue that dietary supplementation can overcome alcohol-induced zinc deficiency and restore alveolar epithelial and macrophage function, and therefore could be an effective treatment for the susceptible alcoholic lung phenotype.

Use of dietary supplements by pregnant and lactating women in North America

Article

Full-text available

Jan 2009
AM J CLIN NUTR

Nutrient requirements increase during periods of growth and development such as pregnancy and lactation. In response, many clinicians recommend dietary supplements during these important periods of the life cycle. Although there exist some recommendations concerning the need for a limited number of nutrients in supplemental form (eg, iron, folic acid, and iodine), there is a relative paucity of data concerning the use of dietary supplements during pregnancy and lactation. Limited data suggest, however, that usage is dependent on demographic, sociologic, and economic factors. Thus, it is possible that the nation's most at-risk populations may be those who are least likely to comply with these recommendations. As researchers continue to study what is meant by "optimal nutrition" during pregnancy and lactation, it is likely that additional recommendations concerning dietary supplements will emerge. For example, it is possible that increased consumption of some of the long-chain polyunsaturated fatty acids during pregnancy or lactation may impart a benefit to infant health. Understanding better the population dynamics related to supplement use during these periods will be critical in implementation of campaigns designed to encourage appropriate use--and discourage inappropriate use--of dietary supplements during these important phases of human reproduction. The purpose of this article is to briefly review what is known about the use of dietary supplements in North America and, more specifically, in pregnant and lactating women. In addition, information concerning barriers to supplement use is discussed as are current recommendations for dietary supplement consumption during these periods of the life cycle.

Iron and copper, and their interactions during development

Article

Full-text available

Jan 2009
BIOCHEM SOC T

During development, the fetus is entirely dependent on the mother for its nutrient requirements. Subsequently, it is a period when both are vulnerable to changes in dietary supply, especially of those nutrients that are marginal under normal circumstances. In developed countries, this applies mainly to micronutrients. Even now, iron deficiency is a common disorder, especially in pregnancy. Similarly, copper intake in the U.K. population is rarely above adequate levels. It is now becoming clear that nutrient deficiencies during pregnancy can result in problems for the offspring, in both the short- and long-term. Early studies showed that lambs born to mothers on copper-deficient pastures developed 'swayback', with neurological and muscular symptoms that could not be reversed by postnatal supplementation. Our own findings have shown that prenatal iron deficiency results in increased postnatal blood pressure, even though the offspring have normal dietary iron levels from birth. These observations emphasize the importance of iron and copper in growth and development. Complicating the situation further is the fact that copper and iron are known to interact with each other in many ways, including absorption and intracellular transport. However, their interactions during the pregnancy appear to be more complex than during the non-pregnant state. In the present review, we examine the importance of these metals and their interactions, the consequences, both short- and long-term, of deficiency and consider some possible mechanisms whereby these effects may be generated.

Regulation and function of Zip4, the acrodermatitis enteropathica gene

Article

Full-text available

Jan 2009
BIOCHEM SOC T

Glen K Andrews

The SLC39A (solute carrier 39A) [ZIP (Zrt-Irt-like protein)] family consists of 14 members which are thought to control zinc uptake into the cytoplasm. Among these, ZIP4 is known to be particularly important for zinc homoeostasis. Mutations in this gene cause acrodermatitis enteropathica, a rare recessive-lethal human genetic disorder. In the present paper, our studies of the regulation and function of the mouse Zip4 gene are briefly reviewed. Mouse Zip4 is expressed at highest levels in tissues involved in absorption of dietary or maternal zinc, and the gene and protein are dynamically regulated by multiple post-transcriptional mechanisms in response to zinc availability. ZIP4 accumulates at the apical surface of enterocytes and endoderm cells when zinc is deficient, because of increased stability of the mRNA and stabilization of the protein. In contrast, when zinc is replenished, the mRNA is destabilized and the protein is internalized and degraded rapidly. The critical importance of ZIP4 in zinc homoeostasis is revealed in mice with targeted deletions of this gene. Homozygous Zip4-knockout embryos die during early morphogenesis and heterozygous offspring are significantly underrepresented and display an array of developmental defects, including exencephalia, anophthalmia and severe growth retardation. Mice heterozygous for Zip4-knockout are hypersensitive to zinc deficiency, which suggests that humans heterozygous for this gene may also be very sensitive to zinc deficiency.

Syndromes, Disorders and Maternal Risk Factors Associated With Neural Tube Defects (VII)

Article

Full-text available

Oct 2008

Chih-Ping Chen

Neural tube defects (NTDs) may be associated with syndromes, disorders and maternal risk factors. This article provides a comprehensive review of the syndromes, disorders and maternal risk factors associated with NTDs, including DK phocomelia syndrome (von Voss-Cherstvoy syndrome), Siegel-Bartlet syndrome, fetal warfarin syndrome, craniotelencephalic dysplasia, Czeizel-Losonci syndrome, maternal cocaine abuse, Weissenbacher- Zweymller syndrome, parietal foramina (cranium bifidum), Apert syndrome, craniomicromelic syndrome, XXagonadism with multiple dysraphic lesions including omphalocele and NTDs, Fryns microphthalmia syndrome, Gershoni-Baruch syndrome, PHAVER syndrome, periconceptional vitamin B6 deficiency, and autosomal dominant Dandy-Walker malformation with occipital cephalocele. NTDs associated with these syndromes, disorders and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes, disorders and maternal risk factors associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.

Teratogenic Effects of Essential Trace Metals: Deficiencies and Excesses

Chapter

Jul 2023

Carl L. Keen

Non-Transferrin-Bound Iron in Alcohol Abusers

Article

Oct 2001

The influence of nutrition during pregnancy upon the condition of the infant at birth

Article

Primary and secondary zinc deficiency as factors contributing to abnormal central nervous system development

Article

Jan 1995

Zinc deficiency is a recognized reproductive hazard. The most common cause of embryonic zinc deficiency is low maternal plasma concentrations of the element, which can occur via numerous routes including the following: inadequate dietary zinc intake, genetic abnormalities in zinc metabolism, disease and drug-induced changes in zinc uptake and excretion, and cytokine-induced changes in zinc metabolism. Evidence is presented that tumor necrosis factor-α is a cytokine whose teratogenicity may be attributed, in part, to its effect on zinc metabolism. The concept that cytokine-induced changes in zinc metabolism represents a common mechanism underlying the developmental toxicity of several diverse toxicants is discussed.

The Effect of Zinc Supplementation on Pregnancy Outcome

Article

Aug 1995

Robert L. Goldenberg

Objective. —To evaluate whether zinc supplementation during pregnancy is associated with an increase in birth weight.Design. —A randomized double-blind placebo-controlled trial.Setting. —Outpatient clinic and delivery service at the University of Alabama at Birmingham.Patients. —Five hundred eighty medically indigent but otherwise healthy African-American pregnant women with plasma zinc levels below the median at enrollment in prenatal care, randomized at 19 weeks' gestational age. Women were subdivided by the population median body mass index of 26 kg/m2 into two groups for additional analyses.Intervention. —Women who were taking a non—zinc-containing prenatal multivitamin/mineral tablet were randomized to receive either a daily dose of 25 mg of zinc or a placebo until delivery.Main Outcome Measures. —Birth weight, gestational age at birth, and head circumference at birth.Results. —In all women, infants in the zinc supplement group had a significantly greater birth weight (126 g, P=.03) and head circumference (0.4 cm, P=.02) than infants in the placebo group. In women with a body mass index less than 26 kg/m2, zinc supplementation was associated with a 248-g higher infant birth weight (P=.005) and a 0.7-cm larger infant head circumference (P=.007). Plasma zinc concentrations were significantly higher in the zinc supplement group.Conclusions. —Daily zinc supplementation in women with relatively low plasma zinc concentrations in early pregnancy is associated with greater infant birth weights and head circumferences, with the effect occurring predominantly in women with a body mass index less than 26 kg/m2.(JAMA. 1995;274:463-468)

Zinc, ethanol, and lipid peroxidation in adult and fetal rats

Article

Dec 1987
BIOL TRACE ELEM RES

Studies were performed on adult and fetal rats receiving either a zinc-deficient (<0.5 ppm) diet and/or ethanol (20%) throughout pregnancy. Liver zinc levels were depressed in fetuses exposed toin utero zinc deficiency, but brain zinc levels were unchanged. Ethanol had no effect on the concentration of zinc in the several fetal and adult tissues studies. Lipid peroxidation, as measured by endogenous levels of malondialdehyde (MDA) increased following food restriction, zinc improverishment, and alcoholism in adult and fetal livers, but not in fetal brains. Generally, levels of MDA were highest when both zinc deficiency and the ingestion of alcohol occurred concurrently. Glutathione (GSH) was depressed by zinc restriction in several adult and fetal tissues, but not in the fetal brain. Ethanol alone had no effect on GSH levels. The activity of the enzyme glutathione peroxidase (GSH-Px) was not changed in either organism by alcohol or zinc deficiency. Overall, the data point to increased lipid peroxidation in maternal and fetal rat tissues following zinc depletion and/or treatment with alcohol and draw attention to the apparent vulnerability of the fetal liver toin utero alcoholism. By contrast, the fetal brain seems to be especially resistant to alcohol and zinc-related lipoperoxidation. An association is suggested between the increased lipoperoxidation accompanying zinc deficiency and reduced levels of GSH, but this does not appear to relate to changes in the activity of GSH-Px. A similar relationship is not evident with respect to the increased levels of MDA in fetal and adult livers following chronic alcohol intoxication. A possible basis for the zinc-GSH interaction is discussed.

Letter: Zinc, acrodermatitis enteropathica, and congenital malformations

Article

Mar 1975

Fetal exposure to ethanol has long-term effects on influenza viral immunity and disease severity

Conference Paper

Dec 2009

The influence of prenatal diet on the mother and child

Article

Jan 1941

Primary and Secondary Zinc Deficiency as Factors Underlying Abnormal CNS Development

Article

Dec 2006
ANN NY ACAD SCI

Iron Regulation in the Developing Rat Brain: Effect of In Utero Ethanol Exposure

Article

Jul 1995
J NEUROCHEM

Fetal alcohol syndrome produces defects that parallel abnormalities associated with early iron deficiency. Hence, we examined the effects of prenatal exposure to ethanol on iron, transferrin, and ferritin concentrations. The subjects were the offspring of pregnant rats fed an ethanol-containing diet (Et), pair-fed an isocaloric control diet (Ct), or fed chow and water. The amounts of iron, transferrin, and ferritin were assessed in three CNS regions (cerebral cortex, subcortical forebrain, and brain-stem). In all three segments of the control rats, iron, transferrin, and ferritin levels decreased during the first 2 postnatal weeks, reached a minimum during week 3, and then rose to adult levels. This pattern was delayed by ethanol treatment, e.g., the minimal concentrations in iron, transferrin, and ferritin in the Et-treated rats were achieved later (3 days, 7 days, and 2 weeks, respectively) than they were in the Ct-treated rats. Ethanol-induced alterations in iron homeostasis persisted into adulthood; iron concentration was reduced, transferrin concentration was unaffected, and ferritin concentration was increased. The net result was that the timely delivery and bioavailability of iron were compromised by ethanol exposure. The defects in iron regulation are permanent and may underlie ethanol-induced abnormalities in iron-dependent growth processes such as myelination.

Effects of Ethanol and Maternal Nutritional Status on Fetal Development

Article

Jan 1985
ALCOHOL CLIN EXP RES

Joanne Weinberg

This study investigated the Interactive effects of alcohol and nutritional status of the pregnant female on fetal growth and development Three liquid diets were formulated ranging in protein content from suboptimal to supraoptimal: diet I provided 18% kcal as protein and 1.0 kcal/ml; diets II and III provided 25 and 32% kcal, respectively, as protein and 1.2 kcal/ml. In all cases, alcohol provided 36% of total calories. Both pair-fed and ad libitum fed control groups were included. We found that blood alcohol levels were consistently high in all three diet regimens throughout gestation. Alcohol intake suppressed weight gains and increased adrenal weights and placenta weights in pregnant females. Both body weights and brain weights were reduced in alcohol-exposed fetuses. However, relative brain weights were found to be increased in alcohol fetuses, indicating “brain sparing.” Maternal nutritional status had no major effect on developmental outcome. Thus, with alcohol administered as a high proportion of total dairy calories, increasing dietary protein levels did not attenuate the major adverse effects of alcohol on fetal development.

The nutrient intakes of mothers of low birth weight babies - A comparison of ethnic groups in East London, UK

Article

Apr 2005
MATERN CHILD NUTR

The objective of this paper was to compare the nutrient intakes of mothers of different ethnic origins after they had given birth to a low birth weight (LBW) baby (<2.5 kg). A total of 165 participants from East London, UK completed a prospective 7-day diet diary using household measures, between 8 and 12 weeks post-partum. The data were originally collected as baseline data prior to two separate nutrition intervention studies and were combined and re-interrogated for the purpose of this paper. Folate and iron intakes were low in all ethnic groups compared to the Reference Nutrient Intakes (RNI). Half did not meet the RNI for folate and 88% did not meet the RNI for iron. Nearly a quarter of the group did not achieve the Lower Reference Nutrient Intake (LRNI) for iron. The mean vitamin D and calcium intakes were significantly different between the ethnic groups (P = 0.007, P = 0.001, respectively). African women had the highest vitamin D intakes (4.72 µg d−1) and Caucasians and Asians the lowest (2.4 µg d−1). Caucasians had the highest calcium intakes (780 mg d−1) and Africans the lowest (565 mg d−1). Over two-thirds of African, Asian and African-Caribbean women did not meet the RNI for calcium. Thirty-one per cent of Africans did not meet the LRNI for calcium. Our data show a high prevalence of inadequate nutrition among women who deliver LBW babies with differences in nutrient intake between ethnic groups. This information can be used to target specific appropriate dietary advice to ethnic minorities for the prevention or repetition of LBW.

Non‐Transferrin‐Bound Iron in Alcohol Abusers

Article

Oct 2001
ALCOHOL CLIN EXP RES

Background: Non-transferrin-bound iron, a low-molecular-weight iron complex capable of initiating free radical formation and lipid peroxidation, has been detected in the serum of animals experimentally fed with alcohol, but no data have been reported in alcohol abusers. The purpose of this study was to evaluate whether non-transferrin-bound iron is present in chronic alcohol abusers with liver involvement and whether alcohol plays any part in its appearance. Methods: We measured non-transferrin-bound iron in a cohort of chronic alcohol abusers with and without liver cirrhosis at presentation, when 43 were active abusers and 33 were abstainers, and in a smaller group during a follow-up period. Results: At presentation, non-transferrin-bound iron was detectable in 83.7% of active abusers but only in 21.2% of abstainers, and within the group of abusers, patients with cirrhosis had significantly higher non-transferrin-bound iron than patients without. Non-transferrin-bound iron was present not only in patients with transferrin saturation >45% but also in those with transferrin saturation ≤45%. Multiple regression analys

The Plausibility of Maternal Nutritional Status Being a Contributing Factor to the Risk for Fetal Alcohol Spectrum Disorders: The Potential Influence of Zinc Status as an Example

Abstract

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