Article

Caffeine Intake During Pregnancy and Risk of Problem Behavior in 5- to 6-Year-Old Children

July 2012
PEDIATRICS 130(2):e305-13

DOI:10.1542/peds.2011-3361

Source
PubMed

Authors:

Odin Van der Stelt

Marcel van der Wal

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Human studies that have investigated the association between caffeine intake during pregnancy and offspring's behavioral outcomes are scant and inconclusive. We prospectively investigated the association between maternal caffeine intake during pregnancy and children's problem behavior at age 5 to 6 years. Mediation by fetal growth restriction and gestational age as well as effect modification by the child's gender and maternal smoking was tested. In a community based multiethnic birth cohort, dietary caffeine intake (coffee, caffeinated tea, and cola) was measured (maternal self-report, n = 8202) around the 16th week of gestation. At age 5, children's overall problem behavior, emotional problems, conduct problems, hyperactivity/inattention problems, peer relationship problems, and prosocial behavior were rated by both mother and teacher (n = 3439) with the Strengths and Difficulties Questionnaire. Analyses were adjusted for maternal age, ethnicity, cohabitant status, education, smoking and alcohol consumption during pregnancy, child's gender, family size, and prenatal maternal anxiety. Caffeine intake was not associated with a higher risk for behavior problems or with suboptimal prosocial behavior. No evidence was found for mediation by fetal growth restriction or gestational age, nor for effect modification by the child's gender. Results did not provide evidence for developmental programming influences of intrauterine exposure to caffeine on offspring's problem behavior at age 5. Present results give no indication to advise pregnant women to reduce their caffeine intake to prevent behavior problems in their children.

Prenatal caffeine exposure: association with neurodevelopmental outcomes in 9‐ to 11‐year‐old children

Article

Full-text available

Jul 2021

Background: Despite the widespread use of caffeine including consumption during pregnancy, the effect of prenatal caffeine exposure on child brain development and behavior is unclear. Methods: To address this, we used data from the Adolescent Brain and Cognitive Development Study (n = 11,875 children aged 9-11 years from 22 sites across the United States). We explored the associations between prenatal caffeine exposure and various developmental outcomes including birth outcomes, physical health, behavior problems, cognition, substance use and brain structure in children, and evaluated dose effects. Results: Among 9,978 children (4,745 females) who had valid data for prenatal caffeine exposure and whose mothers did not use drugs of abuse after knowing of pregnancy, 4,170 (41.79%) had no prenatal caffeine exposure, 2,292 (22.97%) had daily, 1,933 (19.37%) had weekly, and 1,583 (15.86%) had less than weekly exposures. Prenatal caffeine exposure including the widely recommended 'safe' dose was associated with greater externalizing problems, whereas greater BMI and soda consumption were only observed in children with high dose exposures (3+ per day). Notably, the effect size for association of externalizing problems with prenatal caffeine exposure was comparable with that reported for prenatal alcohol (The American Journal of Psychiatry, 177, 2020 and 1060) and prenatal cannabis (JAMA Psychiatry, 78, 2020 and 64) exposures from previous ABCD publications. Additionally, prenatal caffeine exposure was associated with brain structural changes that included greater posterior and lower frontal cortical thickness and altered parietooccipital sulcal depth. Conclusions: The recommended 'safe' dose of caffeine during pregnancy should be carefully studied to assess whether the behavioral and brain correlates observed here are clinically relevant and determine whether it needs adjustment. Because of the high prevalence of caffeine use in the general population, studies on prenatal exposure to drugs of abuse should include prenatal caffeine use as a covariate.

Maternal caffeine consumption and childhood behavioural and neurocognitive development: A focused narrative review

Article

Full-text available

Jun 2021

James Jack E

Maternal Caffeine Intake During Pregnancy and Child Cognition and Behavior at 4 and 7 Years of Age

Article

Nov 2015

Although caffeine is commonly consumed during pregnancy, there are few reports on the association of in utero caffeine exposure with offspring cognition or behavior during childhood. We evaluated the association of maternal serum paraxanthine, caffeine's primary metabolite, at <20 and ≥26 weeks' gestation with the child's intelligence quotient (IQ) and problem behaviors at ages 4 and 7 years among 2,197 mother-child pairs. The mothers were controls from a case-control study of caffeine metabolites and spontaneous abortion that was nested within the Collaborative Perinatal Project (multiple US sites, 1959-1974). Associations of paraxanthine (adjusted for maternal age, race, education, smoking, prepregnancy weight, gestational age at blood draw, and child sex) with mean IQ were assessed by linear regression and associations with problem behaviors by logistic regression. Paraxanthine concentration at ≥26 weeks' gestation manifested an inverted-J-shaped association with child's IQ at age 7 years, with a peak difference (vs. undetectable) of 0.65 points at 750 µg/L (66th percentile) and a decrement thereafter. Paraxanthine at <20 weeks was linearly associated with internalizing behavior at age 4 years (for a 500-µg/L increase, odds ratio = 1.3, 95% confidence interval: 1.1, 1.5). None of the remaining 12 associations approached statistical significance. We conclude that over a range of values applicable to most pregnant women, there was no meaningful association of serum paraxanthine level with childhood IQ or problem behaviors.

Consumo de cafeína durante a gestação e transtorno de déficit de atenção e hiperatividade (TDAH): uma revisão sistemática da literatura

Article

Full-text available

Apr 2015

O objetivo do presente estudo foi avaliar, mediante revisão sistemática da literatura, as evidências acerca da associação entre consumo materno de cafeína durante a gestação e transtorno de déficit de atenção e hiperatividade (TDAH) na infância. A busca na literatura ocorreu de forma sistemática, em múltiplas etapas, nas bases PubMed, LILACS, BIREME e PsycINFO, com limites para artigos publicados em português, inglês e espanhol, realizados em humanos. Foram encontradas 373 referências. Dessas, somente cinco foram mantidas, por atenderem ao objetivo deste estudo. Os cinco trabalhos foram realizados em países desenvolvidos; a maioria utilizou delineamento longitudinal e foi publicada nos últimos cinco anos. Apenas um estudo encontrou associação positiva. Estudos sobre o consumo de cafeína na gestação e TDAH são escassos, com resultados controversos e se deparam com várias dificuldades metodológicas, como falta de padronização na definição do desfecho

[Caffeine consumption during pregnancy and attention deficit hyperactivity disorder (ADHD): a systematic literature review]

Article

Full-text available

Apr 2015
CAD SAUDE PUBLICA

This aim of this study was to conduct a systematic literature review on the association between maternal caffeine intake during pregnancy and attention deficit hyperactivity disorder (ADHD) in childhood. The systematic multiple-stage literature search in PubMed, LILACS, BIREME, and PsycINFO was limited to research in human subjects and published in Portuguese, English, and Spanish. A total of 373 references were retrieved. Of these, only five met the study's objectives and were kept in the review. Most of the studies employed a longitudinal design, were conducted in developed countries, and were published in the last five years. Only one study found a positive association. Studies on caffeine consumption during pregnancy and ADHD are scarce, with conflicting results and several methodological difficulties such as lack of standardized outcome measures.

Maternal caffeine intake during pregnancy and child neurodevelopment up to eight years of age—Results from the Norwegian Mother, Father and Child Cohort Study

Article

Full-text available

Mar 2021
EUR J NUTR

Purpose Current knowledge of the effect of prenatal caffeine exposure on the child’s neurodevelopment is contradictory. The current study aimed to study whether caffeine intake during pregnancy was associated with impaired child neurodevelopment up to 8 years of age.Method A total of 64,189 full term pregnancies from the Norwegian Mother, Father and Child Cohort Study were included. A validated food-frequency questionnaire administered at gestational week 22 was used to obtain information on maternal caffeine intake from different sources. To assess child neurodevelopment (behaviour, temperament, motor development, language difficulties) validated scales were used to identify difficulties within each domain at 6, 18, 36 months as well as 5 and 8 years of age. Adjusted logistic regression models and mixed linear models were used to evaluate neurodevelopmental problems associated with maternal caffeine intake.Results Prenatal caffeine exposure was not associated with a persistently increased risk for behaviour, temperament, motor or language problems in children born at full-term. Results were consistent throughout all follow-ups and for different sources of caffeine intake. There was a minor trend towards an association between consumption of caffeinated soft drinks and high activity level, but this association was not driven by caffeine.Conclusion Low to moderate caffeine consumption during pregnancy was not associated with any persistent adverse effects concerning the child’s neurodevelopment up to 8 years of age. However, a few previous studies indicate an association between high caffeine consumption and negative neurodevelopment outcomes.

Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children

Article

Full-text available

Apr 2017
FOOD CHEM TOXICOL

To date, one of the most heavily cited assessments of caffeine safety in the peer-reviewed literature is that issued by Health Canada (Nawrot et al., 2003). Since then, >10,000 papers have been published related to caffeine, including hundreds of reviews on specific human health effects; however, to date, none have compared the wide range of topics evaluated by Nawrot et al. (2003). Thus, as an update to this foundational publication, we conducted a systematic review of data on potential adverse effects of caffeine published from 2001 to June 2015. Subject matter experts and research team participants developed five PECO (population, exposure, comparator, and outcome) questions to address five types of outcomes (acute toxicity, cardiovascular toxicity, bone and calcium effects, behavior, and development and reproduction) in four healthy populations (adults, pregnant women, adolescents, and children) relative to caffeine intake doses determined not to be associated with adverse effects by Health Canada (comparators: 400 mg/day for adults [10 g for lethality], 300 mg/day for pregnant women, and 2.5 mg/kg/day for children and adolescents). The a priori search strategy identified >5000 articles that were screened, with 381 meeting inclusion/exclusion criteria for the five outcomes (pharmacokinetics was addressed contextually, adding 46 more studies). Data were extracted by the research team and rated for risk of bias and indirectness (internal and external validity). Selected no- and low-effect intakes were assessed relative to the population-specific comparator. Conclusions were drawn for the body of evidence for each outcome, as well as endpoints within an outcome, using a weight of evidence approach. When the total body of evidence was evaluated and when study quality, consistency, level of adversity, and magnitude of response were considered, the evidence generally supports that consumption of up to 400 mg caffeine/day in healthy adults is not associated with overt, adverse cardiovascular effects, behavioral effects, reproductive and developmental effects, acute effects, or bone status. Evidence also supports consumption of up to 300 mg caffeine/day in healthy pregnant women as an intake that is generally not associated with adverse reproductive and developmental effects. Limited data were identified for child and adolescent populations; the available evidence suggests that 2.5 mg caffeine/kg body weight/day remains an appropriate recommendation. The results of this systematic review support a shift in caffeine research to focus on characterizing effects in sensitive populations and establishing better quantitative characterization of interindividual variability (e.g., epigenetic trends), subpopulations (e.g., unhealthy populations, individuals with preexisting conditions), conditions (e.g., coexposures), and outcomes (e.g., exacerbation of risk-taking behavior) that could render individuals to be at greater risk relative to healthy adults and healthy pregnant women. This review, being one of the first to apply systematic review methodologies to toxicological assessments, also highlights the need for refined guidance and frameworks unique to the conduct of systematic review in this field.

Intake of Caffeinated Soft Drinks before and during Pregnancy, but Not Total Caffeine Intake, Is Associated with Increased Cerebral Palsy Risk in the Norwegian Mother and Child Cohort Study

Article

Full-text available

Aug 2016

Background: Postnatal administration of caffeine may reduce the risk of cerebral palsy (CP) in vulnerable low-birth-weight neonates. The effect of antenatal caffeine exposure remains unknown. Objective: We investigated the association of intake of caffeine by pregnant women and risk of CP in their children. Methods: The study was based on The Norwegian Mother and Child Cohort Study, comprising >100,000 live-born children, of whom 222 were subsequently diagnosed with CP. Mothers reported their caffeine consumption in questionnaires completed around pregnancy week 17 (102,986 mother-child pairs), week 22 (87,987 mother-child pairs), and week 30 (94,372 mother-child pairs). At week 17, participants were asked about present and prepregnancy consumption. We used Cox regression models to estimate associations between exposure [daily servings (1 serving = 125 mL) of caffeinated coffee, tea, and soft drinks and total caffeine consumption] and CP in children, with nonconsumers as the reference group. Models included adjustment for maternal age and education, medically assisted reproduction, and smoking, and for each source of caffeine, adjustments were made for the other sources. Results: Total daily caffeine intake before and during pregnancy was not associated with CP risk. High consumption (≥6 servings/d) of caffeinated soft drinks before pregnancy was associated with an increased CP risk (HR: 1.9; 95% CI: 1.2, 3.1), and children of women consuming 3-5 daily servings of caffeinated soft drinks during pregnancy weeks 13-30 also had an increased CP risk (HR: 1.7; 95% CI: 1.1, 2.8). A mean daily consumption of 51-100 mg caffeine from soft drinks during the first half of pregnancy was associated with a 1.9-fold increased risk of CP in children (HR: 1.9; 95% CI: 1.1, 3.6). Conclusions: Maternal total daily caffeine consumption before and during pregnancy was not associated with CP risk in children. The observed increased risk with caffeinated soft drinks warrants further investigation.

Prenatal Caffeine Exposure Impairs Pregnancy in Rats

Article

Full-text available

Jan 2016
INT J FERTIL STERIL

Background: In recent years, concerns have been raised about human reproductive disorders. Caffeine consumption is increasing by the world's population and there is a relationship between caffeine intake and adverse reproductive outcomes. The aim of this study was to evaluate the effects of caffeine on implantation sites, number of live births, birth weight, crown-rump length (CRL) and abnormality in pregnant rats. Materials and methods: In this experimental study, 40 female albino rats (170-190 g) were randomly divided into two experimental and two control groups (n=10/each group). In both experimental groups, animals received caffeine intraperitoneally (IP: 150 mg/kg/day) on days 1-5 of pregnancy. In experimental group 1, treated animals were euthanized on day 7of pregnancy and the number of implantation sites was counted. In experimental group 2, treated animals maintained pregnant and after delivery, the number of live births, birth weight, CRL and abnormality of neonates were investigated. In control group, animals received IP injections of distilled water. Data were analyzed by independent t test. Results: Results showed that administration of caffeine significantly decreased the number of implantation sites, number of live births and CRL as compared with control group (P<0.05). There were no significant differences regarding birth weight and abnormality of neonate rats between experimental and control groups. Conclusion: These results suggest that caffeine caused anti-fertility effect and significantly decreased CRL in neonate rats.

Consumption habits of pregnant women and implications for developmental biology: A survey of predominantly Hispanic women in California

Article

Full-text available

Jul 2013
Nutr J

Healthy post-pregnancy outcomes are contingent upon an informed regimen of prenatal care encouraging healthy maternal consumption habits. In this article, we describe aspects of maternal intake of food, drink, and medication in a population of predominantly Hispanic women in Southern California. Potential implications for unhealthy prenatal dietary choices are discussed. The Food, Beverage, and Medication Intake Questionnaire (FBMIQ) measures common practices of maternal consumption during pregnancy. The FBMIQ was administered to English and Spanish speaking pregnant and recently pregnant (36 weeks pregnant - 8 weeks post-partum) women over the age of 18 who were receiving care from a private medical group in Downey CA. A total of 200 women completed the FBMIQ. Consumption habits of healthy foods and beverages, unhealthy foods, unhealthy beverages, and medication are characterized in this article. Data indicate widespread consumption of fresh fruit, meats, milk and juice and indicate most women used prenatal vitamin supplements. Studies in developmental neuroscience have shown that certain substances may cause teratogenic effects on the fetus when ingested by the mother during pregnancy. Those potentially harmful substances included in our study were Bisphenol-A (BPA), mercury, caffeine, alcohol and certain medications. Our results show that a proportion of the women surveyed in our study consumed BPA, methyl-mercury, caffeine, alcohol, and certain medications at varied levels during pregnancy. This represents an interesting finding and suggests a disconnect between scientific data and general recommendations provided to pregnant mothers by obstetricians. The results of our study demonstrate that a proportion of pregnant women consume substances that are potentially teratogenic and may impact the health and well being of the offspring. It is important to appraise healthy and unhealthy consumption habits in order to encourage healthy practices and alleviate future effects of preventable, toxin-induced developmental issues. Prenatal advising should discourage the consumption of dangerous foods, beverages, and medications that women commonly report eating during pregnancy.

In Utero Exposure to Caffeine and Acetaminophen, the Gut Microbiome, and Neurodevelopmental Outcomes: A Prospective Birth Cohort Study

Article

Full-text available

Jul 2022
Int J Environ Res Publ Health

Pregnant individuals are exposed to acetaminophen and caffeine, but it is unknown how these exposures interact with the developing gut microbiome. We aimed to determine whether acetaminophen and/or caffeine relate to the childhood gut microbiome and whether features of the gut microbiome alter the relationship between acetaminophen/caffeine and neurodevelopment. Forty-nine and 85 participants provided meconium and stool samples at 6–7, respectively, for exposure and microbiome assessment. Fecal acetaminophen and caffeine concentrations were quantified, and fecal DNA underwent metagenomic sequencing. Caregivers and study staff assessed the participants’ motor and cognitive development using standardized scales. Prenatal exposures had stronger associations with the childhood microbiome than concurrent exposures. Prenatal acetaminophen exposure was associated with a trend of lower gut bacterial diversity in childhood [β = −0.17 Shannon Index, 95% CI: (−0.31, −0.04)] and was marginally associated with differences in the relative abundances of features of the gut microbiome at the phylum (Firmicutes, Actinobacteria) and gene pathway levels. Among the participants with a higher relative abundance of Proteobacteria, prenatal exposure to acetaminophen and caffeine was associated with lower scores on WISC-IV subscales. Acetaminophen during bacterial colonization of the naïve gut is associated with lasting alterations in childhood microbiome composition. Future studies may inform our understanding of downstream health effects.

Prenatal smoking, alcohol and caffeine exposure and maternal reported ADHD symptoms in childhood: triangulation of evidence using negative control and polygenic risk score analyses

Article

Full-text available

Nov 2021

Background and aims Studies have indicated that maternal prenatal substance use may be associated with offspring attention deficit hyperactivity disorder (ADHD) via intrauterine effects. We measured associations between prenatal smoking, alcohol and caffeine consumption with childhood ADHD symptoms accounting for shared familial factors. Design First, we used a negative control design comparing maternal and paternal substance use. Three models were used for negative control analyses: unadjusted (without confounders), adjusted (including confounders) and mutually adjusted (including confounders and partner’s substance use). The results were meta-analysed across the cohorts. Second, we used polygenic risk scores (PRS) as proxies for exposures. Maternal PRS for smoking, alcohol and coffee consumption were regressed against ADHD symptoms. We triangulated the results across the two approaches to infer causality. Setting We used data from three longitudinal pregnancy cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK, Generation R study (GenR) in the Netherlands and Norwegian Mother, Father and Child Cohort study (MoBa) in Norway. Participants Phenotype data available for children was: NALSPAC=5,455-7,751; NGENR=1,537-3,119; NMOBA=28,053-42,206. Genotype data available for mothers was: NALSPAC=7,074; NMOBA=14,583. Measurements A measure of offspring ADHD symptoms at age 7-8 years was derived by dichotomising scores from questionnaires and parental self-reported prenatal substance use was measured at the 2nd pregnancy trimester. Findings The pooled estimate for maternal prenatal substance use showed an association with total ADHD symptoms (odds ratio (OR)SMOKING=1.11, 95% confidence interval (CI) 1.00-1.23; ORALCOHOL=1.27, 95%CI 1.08-1.49; ORCAFFEINE=1.05, 95%CI 1.00-1.11), while not for fathers (ORSMOKING=1.03, 95%CI 0.95-1.13; ORALCOHOL=0.83, 95%CI 0.47-1.48; ORCAFFEINE=1.02, 95%CI 0.97-1.07). However, maternal associations did not persist in sensitivity analyses (substance use before pregnancy, adjustment for maternal ADHD symptoms in MoBa). The PRS analyses were inconclusive for an association in ALSPAC or MoBa. Conclusions There appears to be no causal intrauterine effect of maternal prenatal substance use on offspring attention-deficit hyperactivity disorder symptoms.

Prenatal smoking, alcohol and caffeine exposure and ADHD risk in childhood: parental comparisons and polygenic risk score (PRS) analyses

Preprint

Full-text available

Mar 2021

Background and aims: Several studies have indicated that maternal prenatal substance use may be associated with offspring ADHD via intrauterine effects. We investigated associations between maternal prenatal smoking, alcohol and caffeine consumption with childhood ADHD risk accounting for shared familial factors. Design: First, we used a negative control design comparing maternal and paternal substance use. Three models were used for negative control analyses: unadjusted (without confounders); adjusted (including confounders) and mutually adjusted (including confounders and partners substance use). The results were meta-analysed across the cohorts. Second, we used polygenic risk scores (PRS) as proxies for exposures. Maternal PRS for genetic variants of smoking, alcohol and coffee consumption were regressed against ADHD risk. We triangulated the results across the two approaches to infer causality. Setting: We used data from three longitudinal pregnancy cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK, Generation R study (GenR) in the Netherlands and Norwegian Mother, Father and Child Cohort study (MoBa) in Norway. Participants: Phenotype data available for children was: N(ALSPAC)=7,850; N(GENR)=3,849 and N(MOBA)=43,512. Genotype data available for mothers was: N(ALSPAC)=7,074 and N(MOBA)=14,583. Measurements: Offspring ADHD risk around age 7-8 was derived by dichotomising symptom scores from multiple questionnaires and parental self-reported substance use was measured at the 2nd pregnancy trimester. Findings: The pooled estimate for maternal prenatal substance use showed an association with ADHD risk (OR_SMOKING=1.11, 95%CI 1.00-1.23; OR_ALCOHOL=1.27, 95%CI 1.08-1.49; OR_CAFFEINE=1.05, 95%CI 1.00-1.11), while not for fathers (OR_SMOKING=1.03, 95%CI 0.95-1.13; OR_ALCOHOL=0.83, 95%CI 0.47-1.48; OR_CAFFEINE=1.02, 95%CI 0.97-1.07). However, maternal associations did not persist in sensitivity analyses (substance use before pregnancy, adjustment for maternal ADHD in MoBa). The PRS analyses did not show evidence of association in ALSPAC or MoBa. Conclusions: Our results do not provide support for a causal intrauterine effect of maternal prenatal substance use on offspring attention-deficit hyperactivity disorder risk.

Caffeine use during pregnancy: prevalence of use and newborn consequences in a cohort of French pregnant women

Article

Full-text available

Aug 2021
EUR ARCH PSY CLIN N

Many pregnant women, in the world, drink caffeine-containing beverages. Maternal caffeine consumption during pregnancy may have adverse effects on foetus but results are conflicting. Our goals were to estimate the prevalence of caffeine use in a cohort of French pregnant women using maternal self-reports and to evaluate the association between caffeine consumption during pregnancy and delivery and newborn characteristics. All pregnant women who gave birth in a large French urban area during a limited period of time were included (in total 724 mothers were included). Coffee, tea or cola consumption as well as pregnancy and neonate characteristics were analysed. The mean consumption of caffeine per day slightly decreased from the first to the third trimester of pregnancy: 587 caffeine users, with a consumption of caffeine of 59.2 ± 61.5 mg/day during the first trimester as compared to 577 consumers (54.3 ± 55.4 mg/day) during the third trimester, respectively. A significant decrease of neonates’ birth length was observed when mothers were using at least 100 mg/day (or two cups) of caffeine during the second and third trimesters but this difference was no longer significant after adjustment on potential confounding factors such as tobacco use. The potential existence of other confounders (e.g. poorer dietary habits or other lifestyle variables) that might also be associated with reduced birth length, may not be excluded. Caffeine use during pregnancy was associated with reduced birth length but this effect was no longer significant after adjustment on potential confounding variables.

Preconception and Prenatal Nutrition and Neurodevelopmental Disorders: A Systematic Review and Meta-Analysis

Article

Full-text available

Jul 2019

Preconception and prenatal nutrition is critical for fetal brain development. However, its associations with offspring neurodevelopmental disorders are not well understood. This study aims to systematically review the associations of preconception and prenatal nutrition with offspring risk of neurodevelopmental disorders. We searched the PubMed and Embase for articles published through March 2019. Nutritional exposures included nutrient intake or status, food intake, or dietary patterns. Neurodevelopmental outcomes included autism spectrum disorders (ASD), attention deficit disorder-hyperactivity (ADHD) and intellectual disabilities. A total of 2169 articles were screened, and 20 articles on ASD and 17 on ADHD were eventually reviewed. We found an overall inverse association between maternal folic acid or multivitamin supplementation and children’s risk of ASD; a meta-analysis including six prospective cohort studies estimated an RR of ASD of 0.64 (95% CI: 0.46, 0.90). Data on associations of other dietary factors and ASD, ADHD and related outcomes were inconclusive and warrant future investigation. Future studies should integrate comprehensive and more objective methods to quantify the nutritional exposures and explore alternative study design such as Mendelian randomization to evaluate potential causal effects.

Consumption habits of pregnant women in the Jazan region, Saudi Arabia: A descriptive study

Article

Full-text available

Dec 2018
BMC Res Notes

Objective Maternal nutritional habits are critical for the health of both mother and offspring. Postpartum outcomes for mother and infant are strongly influenced by the mother’s nutritional status. Information about consumption habits among pregnant women in Saudi Arabia is scarce. Thus, this study aims to describe the consumption habits of pregnant women in the Jazan region, Saudi Arabia. Results Meat, fish, and fruits were consumed by 97%, 86%, and 90% of the sample. Sugary desserts, fast food, and canned food were consumed by 90%, 81%, and 71% of the sample. Caffeine, juices, and milk were consumed by 75%, 92%, and 81% of the sample. Previous percentages show general higher consumption habits of food and beverages. Over-the-counter medication was used by only 17%. Folic acid, iron, and calcium use by 77%, 64%, and 58% of the sample, respectively. These percentage shows conservative use of Over-the-counter medication and sub-optimal use of important dietary supplements. Moreover, there was a positive association between caffeine intake and trimesters. Furthermore, there was negative association between education level and fish intake. Finally, canned foods consumption was higher among low income pregnant women.

Maternal Caffeine Consumption during Pregnancy and Behavioral Disorders in 11-Year-Old Offspring: A Danish National Birth Cohort Study

Article

Jul 2017

Objective: To examine the association between maternal caffeine consumption from coffee and tea during pregnancy and offspring behavioral disorders. Study design: We studied 47 491 children enrolled in the Danish National Birth Cohort between 1996 and 2002. Data on maternal coffee and tea consumption was collected at 15 and 30 weeks of gestation. When the child was 11 years old, the Strength and Difficulties Questionnaire was filled in by children, parents, and teachers. We estimated risk ratios (RRs) for offspring behavioral disorders. Results: At 15 weeks of gestation 3% and 4% of the pregnant women consumed ≥8 cups/d of coffee or tea, respectively. Maternal coffee consumption ≥8 cups/d at 15 weeks of gestation was associated with increased risk of hyperactivity-inattention disorder (RR 1.47; 95% CI 1.18-1.83), conduct-oppositional disorders (RR 1.22; 95% CI 1.01-1.48), and any psychiatric disorder (RR 1.23; 95% CI 1.08-1.40). Maternal tea consumption ≥8 cups/d at 15 weeks of gestation was associated with increased risk of anxiety-depressive disorders (RR 1.28; 95% CI 1.09-1.52) and any psychiatric disorder (RR 1.24; 95% CI 1.11-1.40). An increased risk of hyperactivity-inattention disorder was observed with increasing daily caffeine consumption at 15 weeks of gestation. Conclusion: High maternal caffeine consumption from coffee and tea at 15 weeks of gestation was associated with behavioral disorders in 11-year-old offspring. We hypothesize that caffeine exposure may affect the fetal brain and program for behavioral disorders later in life. The fetal brain seems to be more sensitive to caffeine exposure at 15 weeks of pregnancy compared with 30 weeks of gestation.

Caffeine

Chapter

Dec 2017

Caffeine, a component of coffee, soft drinks, and chocolate, is widely consumed and considered harmless, although it has powerful effects on a number of organs, systems, and behavior. Caffeine, in typical concentration ranges of human consumption, acts as a nonspecific blocker of the adenosine receptor. Caffeine molecules freely cross biological barriers, reaching the fetus during the entire gestation and can be found in breast milk, reaching breast-fed neonates. The exposure of fetus to caffeine and its metabolites depends on maternal caffeine metabolism, which shows marked genetic and environmental variation. Spontaneous abortion, intrauterine growth restriction, low birth weight, preterm delivery, and decrease in fecundability are major concerns of caffeine exposure. However, little or no reproductive adversity has been consistently associated with caffeine consumption. This chapter focuses on effects of caffeine on fecundability and pre- and postnatal development.

The Influence of Socio-Economic Status on the Prevalence of School-Age Childhood Behavioral Disorders in a Local District Clinic of North West England

Article

Full-text available

Jan 2016

Michael Ogundele

There are several types of childhood behavioral disorders. The most common disruptive behavior disorders include ODD, CD and ADHD. Socio-economic factors are known to influence the prevalence of chronic childhood disabling conditions including emotional and behavioral disorders. Assessment of school-age children for difficult or challenging behavior constitutes a major case load of neurodevelopmental pediatricians (mainly designated as community pediatricians) and child/adolescent psychiatrists in the UK. We aimed to evaluate the influence of the socio-economic status among school-age children on the distribution and types of behavioral disorders, including ADHD, in a local district Community Pediatric unit of a large healthcare NHS Foundation Trust in the North West of England. The record of all the patients who were seen in any outpatient clinic over a 22-month period between Jan 2014 and Oct 2015 were retrospectively analyzed. Information was collected on the range of clinical presentation and socioeconomic characteristics. The socio-economic status of each child was determined using the latest published Index of Multiple Deprivation (IMD) 2015. A total of 201 school-age children were referred (9 monthly), corresponding to an average of 31% of total monthly caseload. The proportion of patients living in the most deprived deciles and quintiles was 39% and 70% respectively. The prevalence in the most deprived decile (11.6/1000) was 193 times that of the most affluent area. History of family and social adversities was common among the patients including separated parents (24%), fostered / adopted (11%) and previous exposure to abuse, domestic violence or neglect (9%). Socioeconomic deprivation is significantly associated with the prevalence of behavior problems in children living in the North-West of England. Poverty-related chronic stressors are hypothesized to cumulatively compromise parental psychology and ultimately childhood behavioral and mental health outcomes. Tackling the problem requires integrated multidisciplinary and multi-agency approach.

The Influence of Socio-Economic Status on the Prevalence of School-Age Childhood Behavioral Disorders in a Local District Clinic of North West England

Article

Full-text available

Aug 2016
JFMHC

Michael Ogundele

There are several types of childhood behavioural disorders. The most common disruptive behavior disorders include ODD, CD and ADHD. Socio-economic factors are known to influence the prevalence of chronic childhood disabling conditions including emotional and behavioural disorders. Assessment of school-age children for difficult or challenging behavior constitutes a major case load of neurodevelopmental pediatricians (mainly designated as community pediatricians) and child/adolescent psychiatrists in the UK. We aimed to evaluate the influence of the socio-economic status among school-age children on the distribution and types of behavioral disorders, including ADHD, in a local district Community Pediatric unit of a large healthcare NHS Foundation Trust in the North West of England. The record of all the patients who were seen in any outpatient clinic over a 22-month period between Jan 2014 and Oct 2015 were retrospectively analyzed. Information was collected on the range of clinical presentation and socioeconomic characteristics. The socio-economic status of each child was determined using the latest published Index of Multiple Deprivation (IMD) 2015. A total of 201 school-age children were referred (9 monthly), corresponding to an average of 31% of total monthly caseload. The proportion of patients living in the most deprived deciles and quintiles was 39% and 70% respectively. The prevalence in the most deprived decile (11.6/1000) was 193 times that of the most affluent area. History of family and social adversities was common among the patients including separated parents (24%), fostered / adopted (11%) and previous exposure to abuse, domestic violence or neglect (9%). Socioeconomic deprivation is significantly associated with the prevalence of behavior problems in children living in the North-West of England. Poverty-related chronic stressors are hypothesized to cumulatively compromise parental psychology and ultimately childhood behavioural and mental health outcomes. Tackling the problem requires integrated multidisciplinary and multi-agency approach.

Caffeine consumption during pregnancy and ADHD at the age of 11 years: A birth cohort study

Article

Full-text available

Dec 2016

Objective Studies evaluating caffeine intake during pregnancy and long-term outcomes, such as the child's neurobehaviour, are still scarce and their results are inconsistent. The objective of the present study was to evaluate the association between maternal consumption of caffeine during pregnancy and attention deficit hyperactivity disorder (ADHD) at the age of 11 years. Methodology All children born in the city of Pelotas, Brazil, during the year 2004, were selected for a cohort study. The mothers were interviewed at birth to obtain information on coffee and yerba mate consumption during pregnancy, among other matters. At the age of 11 years, presence of ADHD was evaluated using the Development and Well-Being Assessment (DAWBA) questionnaire, applied to the mothers. The prevalence of ADHD was calculated, with 95% CIs. The association between caffeine consumption and ADHD was tested by means of logistic regression. Results 3485 children were included in the analyses. The prevalence of ADHD was 4.1% (95% CI 3.4% to 4.7%): 5.8% (95% CI 4.7% to 6.9%) among boys and 2.3% (95% CI 1.5% to 3.0%) among girls. The prevalence of caffeine consumption during the entire pregnancy and in the first, second and third trimesters was 88.7% (87.7% to 89.7%), 86.5% (85.4% to 87.5%), 83.0% (81.8% to 84.2%) and 92.3% (91.4% to 93.1%), respectively. Caffeine consumption during the entire pregnancy and the first, second and third trimesters were not associated with ADHD in the crude or adjusted analysis. Conclusions The present study did not show any association between maternal caffeine consumption during pregnancy and ADHD at the age of 11 years.

Molecular Sciences Zebrafish: A Model for the Study of Toxicants Affecting Muscle Development and Function

Article

Full-text available

Dec 2016
INT J MOL SCI

The rapid progress in medicine, agriculture, and allied sciences has enabled the development of a large amount of potentially useful bioactive compounds, such as drugs and pesticides. However, there is another side of this phenomenon, which includes side effects and environmental pollution. To avoid or minimize the uncontrollable consequences of using the newly developed compounds, researchers seek a quick and effective means of their evaluation. In achieving this goal, the zebrafish (Danio rerio) has proven to be a highly useful tool, mostly because of its fast growth and development, as well as the ability to absorb the molecules diluted in water through its skin and gills. In this review, we focus on the reports concerning the application of zebrafish as a model for assessing the impact of toxicants on skeletal muscles, which share many structural and functional similarities among vertebrates, including zebrafish and humans.

Maternal caffeine exposure alters neuromotor development and hippocampus acetylcholinesterase activity in rat offspring

Article

Nov 2014
BRAIN RES

The objective of this study was to evaluate the effects of maternal caffeine intake on the neuromotor development of rat offspring and on acetylcholine degradation and acetylcholinesterase (AChE) expression in the hippocampus of 14-day-old infant rats. Rat dams were treated with caffeine (0.3 g/L) throughout gestation and lactation until the pups were 14 days old. The pups were divided into three groups: (1) control, (2) caffeine, and (3) washout caffeine. The washout group received a caffeine solution until the seventh postnatal day (P7). Righting reflex (RR) and negative geotaxis (NG) were assessed to evaluate postural parameters as an index of neuromotor reflexes. An open-field (OF) test was conducted to assess locomotor and exploratory activities as well as anxiety-like behaviors. Caffeine treatment increased both RR and NG latency times. In the OF test, the caffeine group had fewer outer crossings and reduced locomotion compared to control, while the washout group showed increased inner crossings in relation to the other groups and fewer rearings only in comparison to the control group. We found decreased AChE activity in the caffeine group compared to the other groups, with no alteration in AChE transcriptional regulation. Chronic maternal exposure to caffeine promotes important alterations in neuromotor development. These results highlight the ability of maternal caffeine intake to interfere with cholinergic neurotransmission during brain development.

Perceptions of self, significant others, and teacher–child relationships in indiscriminately friendly children

Article

Jul 2014
RES DEV DISABIL

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

Article

Full-text available

Jun 2014

Most drugs of abuse easily cross the placenta and can affect fetal brain development. In utero exposures to drugs thus can have long-lasting implications for brain structure and function. These effects on the developing nervous system, before homeostatic regulatory mechanisms are properly calibrated, often differ from their effects on mature systems. In this review, we describe current knowledge on how alcohol, nicotine, cocaine, amphetamine, ecstasy and opiates (among other drugs) produce alterations in neurodevelopmental trajectory. We focus both on animal models and available clinical and imaging data from longitudinal human cohorts. Early studies of fetal exposures focused on classic teratological methods that are insufficient for revealing more subtle effects that are nevertheless very behaviorally relevant. Modern mechanistic approaches have informed us greatly as to how to potentially ameliorate the induced deficits in brain formation and function, but conclude that better delineation of sensitive periods, dose-response relationships, and long-term longitudinal studies assessing future risk of offspring to exhibit learning disabilities, mental health disorders, and limited neural adaptations are crucial to limit the societal impact of these exposures.Neuropsychopharmacology Reviews accepted article preview online, 18 June 2014; doi:10.1038/npp.2014.147.

An Evaluation of Food and Nutrient Intake among Pregnant Women in The Netherlands: A Systematic Review

Article

Full-text available

Jul 2023

Nutritional deficiencies during pregnancy can have serious consequences for the health of the (unborn) child. This systematic review provides an updated overview of the available food and nutrient intake data for pregnant women in The Netherlands and an evaluation based on the current recommendations. Embase, MEDLINE, and national institute databases were used. Articles were selected if they had been published since 2008 and contained data on food consumption, nutrient intake, or the status of healthy pregnant women. A qualitative comparison was made with the 2021 Dutch Health Council recommendations and reference values. A total of 218 reports were included, representing 54 individual studies. Dietary assessments were primarily performed via food frequency questionnaires. Protein, vitamin A, thiamin, riboflavin, vitamin B6, folate, vitamin B12, vitamin C, iron, calcium, and magnesium intakes seemed to be adequate. For folate and vitamin D, supplements were needed to reach the recommended intake. The reasons for concern are the low intakes of fruits, vegetables, and (fatty) fish, and the intakes of alcohol, sugary drinks, and salt. For several foods and nutrients, no or limited intake data were found. High-quality, representative, and recent data are needed to evaluate the nutrient intake of pregnant women in order to make accurate assessments and evaluations, supporting scientific-based advice and national nutritional policies.

Environmental toxins and neurodevelopment

Chapter

Jan 2022

Association between maternal caffeine intake during pregnancy and child development at 6 and 12 months: The Japan Environment and Children's Study

Article

Jun 2022
EARLY HUM DEV

Background: Caffeine intake by pregnant women may have neurodevelopmental effects on the fetus due to adenosine antagonism. However, there are insufficient data and inconsistent results from epidemiological studies on the effect of maternal caffeine intake on child development. Aims: This study examined the association between mothers' estimated caffeine intake during pregnancy and their children's score on the Japanese version of the Ages & Stages Questionnaires™ (J-ASQ) at 6 and 12 months of age. Study design: The study is a part of nationwide prospective birth-cohort study: the Japan Environment and Children's Study. Subjects: In total, 87,106 participants with the Food Frequency Questionnaire (FFQ) data and J-ASQ at 6 or 12 months of age were included in the study. Outcome measures: The data were analyzed by logistic regression analysis to determine whether the scores of the five subscales on the J-ASQ were below the cutoff point as the dependent variable. Results: The results showed that children born to mothers who consumed >300 mg caffeine per day had a 1.11-fold increased odds of gross motor developmental delay at 12 months of age (adjusted odds ratio [AOR] = 1.114 [95 % CI: 1.013-1.226]). Conclusions: Issues in gross motor development can emerge prior to future developmental issues. Therefore, further studies on developmental outcomes in older children, including the future outcomes of the children who participated in this study, are needed.

Prenatal smoking, alcohol and caffeine exposure and offspring externalizing disorders: a systematic review and meta‐analysis

Article

Apr 2022

Background and aims: Several studies have indicated an association between maternal prenatal substance use and offspring externalizing disorders; however, it is uncertain whether this relationship is causal. We conducted a systematic review to determine: (1) if the literature supports a causal role of maternal prenatal substance use on offspring externalizing disorders diagnosis and (2) whether these associations differ across externalizing disorders. Methods: We searched Web of Science, Embase, PsycINFO and Medline databases. Risk of bias assessment was conducted using the Newcastle-Ottawa Scale (NOS), and where possible meta-analysis was conducted for studies classed as low risk of bias. We included studies of any design that examined prenatal smoking, alcohol or caffeine use. Studies in non-English language, fetal alcohol syndrome and comorbid autism spectrum disorders were excluded. Participants in the included studies were mothers and their offspring. Measurements included prenatal smoking, alcohol or caffeine use as an exposure, and diagnosis of attention-deficit hyperactivity disorder (ADHD), conduct disorder (CD) and oppositional defiant disorder (ODD) in offspring as an outcome. Results: We included 63 studies, 46 of which investigated smoking and ADHD. All studies were narratively synthesized, and seven studies on smoking and ADHD were meta-analysed. The largest meta-analysis based on genetically sensitive design included 1 011 546 participants and did not find evidence for an association [odds ratio (OR)1-9 cigarettes = 0.90, 95% confidence interval (CI) = 0.83-1.11; OR > 10 cigarettes = 1.04, 95% CI = 0.79-1.36). Studies on alcohol exposure in all the outcomes reported inconsistent findings and no strong conclusions on causality can be made. Studies on caffeine exposure were mainly limited to ADHD and these studies do not support a causal effect. Conclusions: There appears to be no clear evidence to support a causal relationship between maternal prenatal smoking and offspring attention-deficit hyperactivity disorder. Findings with alcohol and caffeine exposures and conduct disorder and oppositional-defiant disorder need more research, using more genetically sensitive designs.

Caffeine

Chapter

Mar 2022

Caffeine is the most consumed psychostimulant drug with free access to all groups of people through a wide range of dietary and medicinal sources. Caffeine consumption and its effects on fecundability, fetal development, and neonatal life have been thoroughly investigated for a long time. In studies with animals, several negative outcomes related to reproduction and development with caffeine exposure are reported. For example, decrease in birth weight, cardiovascular defects, and behavioral sensitizations to illicit drugs have been observed. However, no animal study can predict accurately the caffeine effects in humans. Even though reproductive-aged women and children are indicated to be at risk, subgroups that may require specific advice on moderating their caffeine intake are yet to be established.

Caffeine exposure in utero is associated with structural brain alterations and deleterious neurocognitive outcomes in 9-10 year old children

Article

Jan 2021
NEUROPHARMACOLOGY

Caffeine, a very widely used and potent neuromodulator, easily crosses the placental barrier, but relatively little is known about the long-term impact of gestational caffeine exposure (GCE) on neurodevelopment. Here, we leverage magnetic resonance imaging (MRI) data, collected from a very large sample of 9157 children, aged 9-10 years, as part of the Adolescent Brain and Cognitive Developmentsm (ABCD ®) study, to investigate brain structural outcomes at 27 major fiber tracts as a function of GCE. Significant relationships between GCE and fractional anisotropy (FA) measures in the inferior fronto-occipito fasciculus and corticospinal tract of the left hemisphere (IFOF-LH; CST-LH) were detected via mixed effects binomial regression. We further investigated the interaction between these fiber tracts, GCE, cognitive measures (working memory, task efficiency), and psychopathology measures (externalization, internalization, somatization, and neurodevelopment). GCE was associated with poorer outcomes on all measures of psychopathology but had negligible effect on cognitive measures. Higher FA values in both fiber tracts were associated with decreased neurodevelopmental problems and improved performance on both cognitive tasks. We also identified a decreased association between FA in the CST-LH and task efficiency in the GCE group. These findings suggest that GCE can lead to future neurodevelopmental complications and that this occurs, in part, through alteration of the microstructure of critical fiber tracts such as the IFOF-LH and CST-LH. These data suggest that current guidelines regarding limiting caffeine intake during pregnancy may require some recalibration.

Caffeine exposure during pregnancy: Is it safe?

Article

Oct 2020
Semin Fetal Neonatal Med

Numerous studies have examined the association between maternal caffeine consumption and infant and childhood health outcomes and the results have been inconsistent. The study of maternal caffeine intake and infant and childhood health outcomes is prone to methodologic challenges. In this review, we examine the existing evidence juxtaposed with the epidemiologic design challenges that color the interpretation of the study results presented. In light of methodologic/interpretation challenges, it seems reasonable to infer that exposure to low levels of caffeine is probably not associated with substantial infant and childhood adversities. However, more research is needed using well designed studies that address methodologic challenges.

Dietary Knowledge, Practices and Adequacy among Bedouin Pregnant Women

Article

Full-text available

Dec 2019

Introduction: Nutrition in pregnancy is usually socio-culturally shaped which marked by different beliefs and values. These beliefs and values yield taboos and myths that greatly shape their lifestyle. Therefore, understanding the client"s culture is an important issue in a culturally congruent nutritional assessment and counseling. Aim of the study: to identify dietary knowledge, practices and adequacy among Bedouin pregnant women. Research design: A descriptive research design. Setting: The outpatient clinic of Marsa-Matrouh maternity hospital, Egypt. Subjects: A convenience sample of 320 pregnant women. Tools: Three tools were utilized for data collection: Tool I: Pregnant women"s basic data structured interview schedule Tool II: Pregnant women"s Dietary knowledge structured interview schedule and Tool III: Pregnant women"s dietary practices structured interview schedule. Results: Only 4.7% of the study subjects have good knowledge about nutrition during pregnancy. As much as 81.6% of them had fair knowledge and only 13.8 % had poor knowledge. Moreover, there is a statistically significant positive correlation between subject"s level of knowledge about nutrition during pregnancy and energy, protein, calcium and copper dietary adequacy(0.034, 0.052, 0.026, and 0.037, respectively.)Conclusion: the majority of the study subjects had fair level of knowledge about nutrition during pregnancy. Almost two-thirds of them had inadequate intake of most nutrients according to recommended dietary allowance (RDA) for pregnant women. Their level of knowledge about nutrition was positively correlated with their dietary adequacy.

Food Consumption, Nutrient Intake and Status during the First 1000 days of Life in the Netherlands: a Systematic Review

Article

Full-text available

Apr 2019

Adequate nutrition is essential for growth and development in early life. Nutritional data serves as a basis for national nutritional guidelines and policies. Currently, there is no insight into the availability of such data during the first 1000 days of life. Therefore, a systematic review was performed, following the PRISMA reporting guideline, to identify studies on food consumption, nutrient intake or status in the Netherlands. Potential gaps were identified, and the quality of the studies is discussed. The databases Embase and Medline were used, as well as databases from national institutes. Articles published in 2008–2018 were screened by two independent reviewers. In total 601 articles were identified, of which 173 were included. For pregnant women, 32 studies were available with nutritional data, for young children 40 studies were identified. No studies were available for breastfeeding women. A large variety of foods and nutrients were assessed, however certain nutrients were lacking (e.g., vitamin K). Overall, the studies had methodological limitations, making the data unsuitable to assess nutrient inadequacies. There is a need for recent, high quality nutritional research to strengthen the understanding of the nutritional needs and deficiencies during early life, and is fundamental for national guidelines and policies.

Kaffee – Gefahr oder Nutzen für die Gesundheit?

Article

Mar 2019

Summary: Several studies have shown that coffee drinkers live longer due to having a lower risk of many diseases. The strongest effect is seen for 3–5 cups per day. But the health effects of regular coffee consumption are quite controversial. Depending on the research context, it is either a healthy beverage or in some cases harmful. Coffee is high in antioxidants and linked to a reduced risk of many diseases. However, it also contains the main active compound caffeine, a stimulant that can cause a short-term boost in energy levels, brain function, metabolic rate and exercise performance but various problems in some people as well, especially in those with known cardiovascular risks or diseases. Coffee may lower the risk of type 2 diabetes and is beneficial in blood pressure regulation in the longterm. Coffee drinkers have a significantly lower risk of cirrhosis and liver cancer. The more coffee they drink, the lower the risk. Recently caffeine and metabolites have been detected as reliable biomarkers of early Parkinson disease. Caffeine exposure during gestation may affect the fetal brain and program for behavioral disorders later in life. The review takes a detailed look at regular coffee consumption and its health effects, examining both the pros and cons.

Substance Use Disorders in Perinatal Period

Chapter

Full-text available

Jan 2019

Epidemiological data revealed an increasing consume of both ‘legal’ (i.e., tobacco, alcohol) and illegal substances amongst women of childbearing age, during the last decades, with a subsequent increasing risk of teratogenesis and perinatal complications for foetus of pregnant women exposed to substances of abuse/misuse. The early identification and management of women at risk of Substance Use Disorders (SUDs) in pregnancy, may help clinicians in promptly applying specifically-targeted harm reductions interventions. The present chapter aims at providing a comprehensive overview on birth defects, foetal malformations, teratogenic risk and perinatal complications related to the consume of cannabinoids, opioids and psychostimulant drugs during pregnancy. Practical recommendations on how to manage a pregnant woman with a SUD (with and/or without a comorbid psychiatric disorder) has been as well here provided, from a pharmacological and nonpharmacological point of view.

A Biological/Genetic Perspective: The Addicted Brain: Evidence-Based Approaches to Prevention and Treatment

Chapter

Aug 2018

Exposure to psychoactive drugs presents a significant health risk during human development, particularly during critical periods of organ and system development. Exposure to psychoactive drugs of abuse can occur postnatally through passive exposure from environmental sources (e.g., tobacco smoke). Developmental exposure to drugs of abuse among children and adolescents has escalated as drugs have become increasingly accessible. This chapter will examine the health risks associated with developmental exposure to psychoactive drugs of abuse. The epidemiology of caffeine, nicotine, alcohol, marijuana, opiates and therapeutic stimulants exposure will be summarized, and research examining the neurodevelopmental and other health consequences of developmental drug exposure will be reviewed. While it remains difficult to isolate direct causal influences and disentangle the direct effects of drug exposure from indirect effects associated with environmental, social, and cultural influences that are often closely associated with drug exposure, compelling evidence suggests that developmental exposure to drugs of abuse can have both subtle and dramatic effects with important behavioral and societal consequences.

Maternal caffeine intake in pregnancy is inversely related to childhood peer problems in Japan: The Kyushu Okinawa Maternal and Child Health Study

Article

Mar 2018

Objectives: The present prebirth cohort study examined the association between maternal caffeine consumption during pregnancy and behavioral problems in Japanese children aged 5 years. Methods: Subjects were 1199 mother–child pairs. Dietary intake was assessed using a diet history questionnaire. Emotional problems, conduct problems, hyperactivity problems, and peer problems were assessed using the Japanese parent-report version of the Strengths and Difficulties Questionnaire. Adjustment was made for maternal age, gestation at baseline, region of residence at baseline, number of children at baseline, maternal and paternal education, household income, maternal depressive symptoms during pregnancy, maternal alcohol intake during pregnancy, maternal smoking during pregnancy, child’s birth weight, child’s sex, breastfeeding duration, and smoking in the household during the first year of life. Results: The contributors of caffeine in the diet during pregnancy were Japanese and Chinese tea (74.8%), coffee (13.0%), black tea (4.4%), confectionaries (4.0%), and soft drinks (3.7%). Higher maternal caffeine consumption during pregnancy was independently associated with a reduced risk of peer problems in the children: the adjusted odds ratios (95% confidence intervals) in the first, second, third, and fourth quartiles of maternal caffeine consumption during pregnancy were 1 (reference), 0.61 (0.35–1.06), 0.52 (0.29–0.91), and 0.51 (0.28–0.91), respectively (P for trend = 0.01). Maternal caffeine intake during pregnancy was not evidently related to the risk of emotional problems, conduct problems, or hyperactivity problems in the children. Conclusions: Maternal caffeine consumption, mainly from Japanese and Chinese tea, during pregnancy may be preventive against peer problems in Japanese children.

Maternal substance use during pregnancy and offspring conduct problems: A meta-analysis

Article

Aug 2017
NEUROSCI BIOBEHAV R

We conducted meta-analyses of relationships between highly prevalent substance use during pregnancy and offspring conduct disorder problems. In total 36 studies were included. Odds ratios (ORs) were 2.06 (1.67-2.54, 25 studies) for maternal smoking, 2.11 (1.42-3.15, 9 studies) for alcohol use, and 1.29 (0.93-1.81, 3 studies) for cannabis use, while a single study of caffeine use reported no effects. Our meta-analyses support an association between smoking and alcohol use during pregnancy, and offspring conduct problems, yet do not resolve causality issues given potential confounding by genetic factors, gene-environment interactions, and comorbidity such as with attention deficit hyperactivity disorders. Future studies should use genetically sensitive designs to investigate the role of pregnancy substance use in offspring conduct problems and may consider more broadly defined behavioral problems.

Adenosine Receptors in Neurodegenerative Diseases

Book

Mar 2017

David Blum

Adenosine Receptors in Neurodegenerative Diseases covers the role of adenosine receptors in brain function, also focusing on related methodologies and perspectives in therapeutics. The book provides an up-to-date overview by the best specialists in the field, helping readers consider the importance of adenosine and expand the global impact and visibility of adenosine research in the CNS field. Chapters include adenosine biology and signaling, gene regulation, control of motor function, and novel adenosine-based therapies in the CNS. It is an ideal resource for researchers, advanced graduate students, clinicians, and industry scientists working in the fields of clinical neuroscience and molecular and cellular neuroscience.

Extensive literature search as preparatory work for the safety assessment for caffeine

Article

Jan 2015

HABITUALCAFFEINE CONSUMPTION AND ITS INFLUENCE ON MYOCARDIAL FIBERS, BLOOD PRESSURE AND OXIDATIVE STATUS IN PREGNANT ALBINO WISTAR RATS.

Article

Full-text available

Oct 2016

Neurobehavioral Aspects of Caffeine

Chapter

Dec 2016

Rob Hughes

The psychomotor stimulant caffeine is the most widely consumed drug in existence. It is present in a number of beverages, foods, and medicines, and exerts its behavioral effects mainly by antagonism of adenosine A1 and A2A receptors. Although tolerance can develop to some of its physiological effects, there is currently little evidence for tolerance to its behavioral actions and subsequent dependence. Depending on dose, baseline arousal level and whether or not reversal of withdrawal occurs, caffeine can improve or impair psychomotor performance. Although it may improve impaired memory, there is less evidence for a similar effect on unimpaired memory in humans. When they do occur, improvements in memory are probably mainly due to effects on arousal, concentration, or reversal of withdrawal, rather than consolidation. Caffeine can be either anxiogenic or anxiolytic, depending on dose. There is no evidence that caffeine will affect physical or behavioral development in humans, although some animal research suggests that perinatal or adolescent exposure my lead to heightened anxiety in adulthood.

Review On Health Effects Of Foods Avoided By Literate Bangladeshi Women During Pregnancy.

Article

Full-text available

Jan 2015

Mariz Sintaha

Caffeine Exposure During Late Chick Embryogenesis Alters Hatchability and Plasma Thyroid Hormone Levels

Article

Full-text available

Sep 2014

To evaluate the consequences of exposure to caffeine during the final week of embryogenesis, we treated chick embryos with caffeine (20 μmol/egg) on day 15 and examined them and the hatchlings' behavior. Of the control embryos, more than 85% hatched on day 21, whereas 75% of the caffeine-treated embryos hatched on day 20. The caffeine hatchlings did not have significant malformations. The caffeine hatchlings on day 20 showed a significantly decreased tissue weight (mg) of the telencephalon (391.7±7.5 vs. 451.8±4.6), optic lobe (139.6±2.1 vs. 157.9±4.9), cerebellum (106.9±2.4 vs. 126.8±3), and brain stem (171.4±4.1 vs. 203.1±7.5) compared to the controls on day 21. The weights did not reach the control levels during the experimental period. The hatchlings' behaviors were evaluated using the imprinting ability test (assessing recognition and memory) and social behavior tests (aggregation, belongingness, and vocalization activity). These were designed to examine their willingness to find each other and form a group. None of the behavior tests showed significant differences between the caffeine-treated and the control hatchlings. Marked elevation of the duodenum alkaline phosphatase activity and the plasma triiodothyronine level were observed before hatching during normal development. The caffeine-treated group showed the increase in parallel 1 day earlier. Since thyroid hormone is involved in brain and gut maturation during the final week of embryogenesis, it is suggested that caffeine exposure accelerated the elevation of the hormone, which affects the maturation of brain quality related to imprinting and behavior and necessary gut maturation in hatchlings.

Early Life Influences on Cognition, Behavior, and Emotion in Humans: From Birth to Age 20

Article

Oct 2015

The long-lasting effects of fetal exposure to early life influences (ELI) such as maternal anxiety, stress, and micronutrient deficiencies as well as mediating and moderating factors are quite well established in animal studies, but remain unclear in humans. Here, we report about effects on cognition, behavior, and emotion in offspring aged 5-20 years old in two prospective longitudinal birth cohorts.

Reversible neuronal and muscular toxicity of caffeine in developing vertebrates

Article

Jun 2014
COMP BIOCHEM PHYS C

This study utilizes zebrafish embryos to understand the cellular and molecular mechanisms of caffeine toxicity in developing vertebrate embryos. By using high concentration of caffeine, we observed almost all the phenotypes that have been described in humans and/or in other animal models, including neural tube closure defect, jittery, touch insensitivity, and growth retardation as well as a drastic coiled body phenotype. Zebrafish embryos exposed to 5 mM caffeine exhibited high frequent movement, 10 moves/min comparing with around 3 moves/min in control embryos, within half an hour post exposure (HPE). They later showed twitching, uncoordinated movement, and eventually severe body curvature by 6 HPE. Exposure at later stages resulted in the same phenotypes but more posteriorly. Surprisingly, when caffeine was removed before 6 HPE, the embryos were capable of recovering but still exhibited mild curvature and shorter bodies. Longer exposure caused irreversible body curvature and lethality. These results suggest that caffeine likely targets the neuro-muscular physiology in developing embryos. Immunohistochemistry revealed that the motorneurons in treated embryos developed shorter axons, abnormal branching, and excessive synaptic vesicles. Developing skeletal muscles also appeared smaller and lacked the well-defined boundaries seen in control embryos. Finally, caffeine increases the expression of genes involved in synaptic vesicle migration. In summary, our results provide molecular understanding of caffeine toxicity on developing vertebrate embryos.

Maternal Long-Chain Polyunsaturated Fatty Acid Status during Early Pregnancy and Children's Risk of Problem Behavior at Age 5-6 Years

Article

Jan 2014

DHPS-44525-risky-exposures-during-pregnancy--a-pilot-study-from-lebanes 051413

Data

Full-text available

Jun 2013

Background: The harmful effects of medication and licit substance use during pregnancy may potentially constitute a major public health concern. Our study aims to assess risky exposure of Lebanese pregnant women to drugs, tobacco, caffeine, and alcohol, and to determine their effect on postnatal outcomes. Methods: Women at term were addressed after delivery in five university hospitals of Beirut and Mount Lebanon between February and June 2012. A standardized questionnaire was administered to them. Moreover, medical files of both mothers and their respective newborns were checked to confirm information given by mothers, and to assess the health outcome of the babies. Results: Among the interviewed 350 women, active and passive smoking of tobacco (cigarette or water pipe), and consumption of category C, D, and X drugs were common during pregnancy in Lebanon; they were shown to negatively affect the neonatal outcome in multivariate analyses: they significantly decreased Apgar scores and increased the risk of underweight and medical complications of babies (P , 0.05). Conclusion: Our study demonstrated that Lebanese women were exposed during pregnancy to multiple medications and licit substances that affected the neonates’ health. Our findings have implications for clinical obstetric practice and prevention programs in Lebanon. Efforts should be made to decrease exposure to harmful substances during pregnancy.

Risky substance exposure during pregnancy: A pilot study from Lebanese mothers

Article

Full-text available

May 2013

The harmful effects of medication and licit substance use during pregnancy may potentially constitute a major public health concern. Our study aims to assess risky exposure of Lebanese pregnant women to drugs, tobacco, caffeine, and alcohol, and to determine their effect on postnatal outcomes. Women at term were addressed after delivery in five university hospitals of Beirut and Mount Lebanon between February and June 2012. A standardized questionnaire was administered to them. Moreover, medical files of both mothers and their respective newborns were checked to confirm information given by mothers, and to assess the health outcome of the babies. Among the interviewed 350 women, active and passive smoking of tobacco (cigarette or water pipe), and consumption of category C, D, and X drugs were common during pregnancy in Lebanon; they were shown to negatively affect the neonatal outcome in multivariate analyses: they significantly decreased Apgar scores and increased the risk of underweight and medical complications of babies (P < 0.05). Our study demonstrated that Lebanese women were exposed during pregnancy to multiple medications and licit substances that affected the neonates' health. Our findings have implications for clinical obstetric practice and prevention programs in Lebanon. Efforts should be made to decrease exposure to harmful substances during pregnancy.

Discriminant validity of the Child Behaviour Checklist CBCL-4/18 in German samples

Article

Full-text available

Dec 2001

This study examined the discriminant validity of the German version of CBCL in two large samples of referred and non-referred children and adolescents which were matched for age, sex and socio-economic status. The combined sample that was used for statistical analysis consists of 2,058 referred and 2,058 non-referred boys and girls between 4 and 18 years of age (mean age: referred boys=10.9 years, non-referred boys=10.9 years, referred girls=11.3 years, non-referred girls=11.1 years). Referral status was used as validity criterion. Statistical procedures included Odds Ratios, Total Predictive Values, ROC analyses and discriminant analyses. Results indicated that the discriminant validity of the German version of CBCL is comparable to the original English version. With the use of CBCL Total Problem Score as predictor (cut-off T≥ 60) 83.8 % of children and adolescents could correctly be classified (sensitivity 83.6 %, specificity 83.9 %). Symptoms of the “Attention Problems Scale” show the highest discriminative power to distinguish between disturbed and undisturbed children and adolescents.

Evaluation of the Reproductive and Developmental Risks of Caffeine

Article

Full-text available

Apr 2011
BIRTH DEFECTS RES B

A risk analysis of in utero caffeine exposure is presented utilizing epidemiological studies and animal studies dealing with congenital malformation, pregnancy loss, and weight reduction. These effects are of interest to teratologists, because animal studies are useful in their evaluation. Many of the epidemiology studies did not evaluate the impact of the "pregnancy signal," which identifies healthy pregnancies and permits investigators to identify subjects with low pregnancy risks. The spontaneous abortion epidemiology studies were inconsistent and the majority did not consider the confounding introduced by not considering the pregnancy signal. The animal studies do not support the concept that caffeine is an abortafacient for the wide range of human caffeine exposures. Almost all the congenital malformation epidemiology studies were negative. Animal pharmacokinetic studies indicate that the teratogenic plasma level of caffeine has to reach or exceed 60 µg/ml, which is not attainable from ingesting large amounts of caffeine in foods and beverages. No epidemiological study described the "caffeine teratogenic syndrome." Six of the 17 recent epidemiology studies dealing with the risk of caffeine and fetal weight reduction were negative. Seven of the positive studies had growth reductions that were clinically insignificant and none of the studies cited the animal literature. Analysis of caffeine's reproductive toxicity considers reproducibility and plausibility of clinical, epidemiological, and animal data. Moderate or even high amounts of beverages and foods containing caffeine do not increase the risks of congenital malformations, miscarriage or growth retardation. Pharmacokinetic studies markedly improve the ability to perform the risk analyses.

Cohort Profile: The Amsterdam Born Children and their Development (ABCD) Study

Article

Full-text available

Oct 2011
INT J EPIDEMIOL

Ethnic differences in mental health among incarcerated youths: Do Moroccan immigrant boys show less psychopathology than native Dutch boys?

Article

Full-text available

May 2010
EUR CHILD ADOLES PSY

Psychiatric disorders are highly prevalent among incarcerated youth. However, whereas ethnic minority youths are overrepresented in the juvenile justice system, limited research is available on their mental health. In this study, differences in mental health problems between incarcerated adolescents of native Dutch and Moroccan origin, were examined. Child Behavior Checklist and Youth Self-Report scores were compared between incarcerated adolescents of native Dutch and Moroccan origin. Their scores were also compared to those of native Dutch and Moroccan immigrant youths in the general, non-incarcerated population. Native Dutch incarcerated adolescents showed higher levels of various mental health problems than incarcerated adolescents with a Moroccan background. Compared to the general population, incarcerated youths showed higher levels of mental health problems, but this deviation was much larger for native Dutch than for Moroccan immigrant youths. These ethnic differences in mental health problems could not be explained by ethnic differences in socio-economic background and social desirable answering tendencies. Incarcerated youths of Moroccan origin show less psychopathology than incarcerated native Dutch youths, which might be explained by disparities in sentencing procedures.

The Prevalence of ADHD-Like Symptoms in a Community Sample

Article

Full-text available

Apr 2010
J Attention Disord

The aim of the present study was to explore the prevalence of ADHD symptoms in a community sample of children in the United Kingdom. There were 964 ten year olds (55% boys; M = 10.4 years; SD = 0.6) from mainstream schools in the United Kingdom in this study. The ADHD Rating Scale-IV, which provides ratings on the frequency of ADHD symptoms drawn from DSM-IV criteria, was administered to class teachers. The findings indicated an overall 8% prevalence rate, with the majority of children identified as the Hyperactive/Impulsive subtype (5%). Almost half of these children were receiving additional support in the classroom as a result of learning difficulties. It is therefore of value for educators to be able to conduct early screening to support these children before problems worsen.

Child/Adolescent Behavioral and Emotional Problems: Implications of Cross-Informant Correlations for Situational Specificity

Article

Full-text available

Apr 1987

Our purpose in this article was to determine the degree of consistency between different informants’ reports of the behavioral/emotional problems of subjects aged from 1½ to 19 years. We found 269 samples in 119 studies for meta-analyses of Pearson r s between ratings by parents, teachers, mental health workers, observers, peers, and the subjects themselves. The mean r s between all types of informants were statistically significant. The mean r s were .60 between similar informants (e.g., pairs of parents), .28 between different types of informants (e.g., parent/teacher), and .22 between subjects and other informants. Correlations were significantly higher for 6- to 11-year-olds than for adolescents, and for undercontrolled versus overcontrolled problems, although these differences were not large. The modest correlations between informants indicate that child and adolescent problems are not effectively captured by present-versus-absent judgments of problems. Instead, the variations between reports by different informants argue for assessment in terms of multiple axes designed to reflect the perceived variations in child and adolescent functioning.

Gestational caffeine modifies offspring behavior in mice

Article

Full-text available

Feb 1981

Dams from two strains of mice, BALB/c C57BR were tested during gestation with caffeine, at doses of about 60, 80 and 100 mg/kg/day, in their drinking water. The resulting offspring were behaviourally tested over a 6-month period commencing at age 9 months. When compared with controls, mice from dams that had received caffeine demonstrated longer latencies in a passive avoidance test, and differences were also noted for female C57BR offspring in activity and habituation measures. Having controlled as far as possible for post-natal maternal and environmental effects, the most likely conclusion is that caffeine has a direct pharmacological action on the foetus, and should therefore be classed as a behavioural teratogen in mice.

Mothers' Mental Illness and Child Behavior Problems: Cause-Effect Association or Observation Bias?

Article

Full-text available

Jun 2000
J AM ACAD CHILD PSY

A number of studies have consistently found that a mother's mental health (particularly her level of depression) is a strong predictor of mental health problems experienced by her child(ren). However, the validity of this finding is in doubt because the majority of these studies have relied on maternal reports as indicators of children's behavior. This prospective, longitudinal study examines data on the mental health of the mother from prior to the birth of her child to when the child reaches 14 years of age. Child behavior is measured at 14 years of age using reports from mother and child. Mother and child responses are compared to provide an indication of the possible magnitude of maternal observation bias in the reporting of child behavior problems. Anxious and/or depressed mothers tend to report more cases of child behavior problems than do their mentally healthy counterparts or children themselves. Differences between mothers and youths in reporting behavior problems appear to be related to the mothers' mental health. Current maternal mental health impairment appears to have a substantial effect on the reporting of child behavior problems by the mother, thereby raising questions about the validity of reports of child behavior by persons who are currently emotionally distressed.

Behavioral Outcomes and Evidence of Psychopathology Among Very Low Birth Weight Infants at Age 20 Years

Article

Full-text available

Oct 2004
Pediatrics

Information on the mental health of very low birth weight (VLBW; <1500 g) children in young adulthood is sparse. We thus sought to examine gender-specific behavioral outcomes and evidence of psychopathology in a cohort of VLBW young adults at 20 years of age. We compared a cohort of 241 survivors among VLBW infants who were born between 1977 and 1979 (mean birth weight: 1180 g; mean gestational age at birth: 29.7 weeks), 116 of whom were men and 125 of whom were women, with 233 control subjects from the same population in Cleveland who had normal birth weights (108 men and 124 women). Young adult behavior was assessed at 20 years of age with the Achenbach Young Adult Self-Report and the Young Adult Behavior Checklist for parents. In addition, the young adults and parents completed the ADHD Rating Scale for Adults. Gender-specific outcomes were adjusted for sociodemographic status. VLBW men reported having significantly fewer delinquent behaviors than normal birth weight (NBW) control subjects, but there were no differences on the Internalizing, Externalizing, or Total Problem Behavior scales. Parents of VLBW men reported significantly more thought problems for their sons than did parents of control subjects. VLBW women reported significantly more withdrawn behaviors and fewer delinquent behavior problems than control subjects. Their rates of internalizing behaviors (which includes anxious/depressed and withdrawn behaviors) above the borderline clinical cutoff were 30% versus 16% (odds ratio: 2.2; 95% confidence interval [CI]: 1.2-4.1). Parents of VLBW women reported significantly higher scores for their daughters on the anxious/depressed, withdrawn, and attention problem subscales compared with control parents. The odds ratios for parent-reported rates above the borderline-clinical cutoff among women for the anxious/depressed subscale was 4.4 (95% CI: 1.4-13.5), for thought problems was 3.7 (95% CI: 1.2-11.6), and for attention problems was 2.4 (95% CI: 1.0-5.5). There were no differences in the young adult self-report of attention-deficit/hyperactivity disorder (ADHD). Parents of VLBW men reported higher mean scores on the attention subtype of ADHD but not higher rates of ADHD. The increase in psychopathology among VLBW survivors in young adulthood indicates a need for anticipatory guidance and early intervention that might help to prevent or ameliorate potential psychopathology.

Beverage caffeine intake in US consumers and subpopulations of interest: Estimates from the Share of Intake Panel survey

Article

Full-text available

Jan 2005
FOOD CHEM TOXICOL

Concerns exist about the potential adverse health effects of high consumption of dietary caffeine, especially in children and pregnant women. Recommended caffeine intakes corresponding to no adverse health effects have been suggested recently for healthy adults (400-450 mg/day), for women contemplating pregnancy (300 mg/day), and for young children age 4-6 years (45 mg/day). To determine whether current caffeine intake approaches these levels, intake from major dietary sources (coffee, tea and carbonated soft drinks) were measured in 10,712 caffeinated beverage consumers in the 1999 US Share of Intake Panel, a targeted beverage survey. Mean caffeine intakes in adult caffeinated beverage consumers ranged from 106 to 170 mg/day (90th percentile intake was 227-382 mg/day). In children 1-5 and 6-9 years, mean caffeine intakes were 14 and 22 mg/day, respectively; corresponding 90th percentile intakes were 37 and 45 mg/day. Pregnant women consumed an average of 58 mg/day (157 mg/day at the 90th percentile), and women of reproductive age ingested 91-109 mg/day (229-247 mg/day at the 90th percentile). These data show that while mean caffeine intakes are within recommended safe levels, heavy consumers of certain subpopulations, including young children and women contemplating pregnancy, might benefit from dietary advice.

Psychosocial and Academic Characteristics of Extremely Low Birth Weight (≤800 g) Adolescents Who Are Free of Major Impairment Compared With Term-Born Control Subjects

Article

Full-text available

Jan 2005
Pediatrics

To compare academic and cognitive ability, attention, attitudes, and behavior of extremely low birth weight (ELBW) adolescents who are free of major impairments at 17 years of age with term-born control subjects. Between January 31, 1981, and February 9, 1986, 250 infants of < or =800 g were admitted for intensive care in British Columbia, 98 (39%) of whom survived to late adolescence. Teens with major sensorimotor handicaps and/or IQ <70 were excluded (n = 19). Of the 79 eligible ELBW teens, 53 (67%) were assessed at 17.3 (16.3-19.7) years (birth weight: 720 [520-800 g]; gestation: 26 [23-29] weeks). The test battery screened the following areas: cognitive (Wechsler Intelligence Scale for Adults Third Edition, 3 subtests), academic (Wide Range Achievement Test-3), attention (Connors' Continuous Performance Task), self-report (Harter Self-Perception Profile for Adolescents; Job Search Attitude Inventory), and parent report (Child Behavior Check List). A comparison group of term born control subjects (n = 31) were also assessed (birth weight: 3506 [3068-4196] g; gestation: 40 [39-42] weeks) at age 17.8 (16.5-19.0) years. Multivariate analysis of variance (group x gender) was conducted for each domain (cognitive, academic, self-report, and parent report). The ELBW group showed lower cognitive scores (vocabulary, block design, and digit symbol) and academic skills (reading and arithmetic) compared with control subjects, with no gender differences. There were no differences in attention between the 2 groups using a repetitive computer task. ELBW teens reported lower scholastic, athletic, job competence, and romantic confidence and viewed themselves as more likely to need help from others in finding a job. In the behavioral domain, parents reported their ELBW teens to display more internalizing, more externalizing, and more total problems than the control teens, with ELBW boys showing more problems. ELBW teens showed a higher percentage of clinically significant behavior problems than control subjects. In a provincial cohort of unimpaired survivors of birth weight < or =800 g, psychosocial and educational vulnerabilities persist into late adolescence and may complicate the transition to adult life compared with their peers.

Fetal Growth and Childhood Behavioral Problems: Results from the ALSPAC Cohort

Article

Full-text available

Jun 2006
AM J EPIDEMIOL

Using data on 4,813 children from the ALSPAC cohort in Bristol, United Kingdom, recontacted in 1998-1999, the authors investigated whether intrauterine growth restriction (indexed by birth weight and length) was associated with behavioral problems at age 7 years. Childhood behavioral problems were measured by using a brief behavioral screening questionnaire (the Strengths and Difficulties Questionnaire (parental completion)). For term singleton infants, a one standard deviation increase in birth weight was associated with an 11% reduction in the odds of behavioral problems at age 81 months. After adjustment for confounders and birth length, this association was no longer seen. The association with birth length remained after adjustment for confounders. A one standard deviation increase in birth length was associated with a 14% decrease in the odds of being in the top tertile of total behavioral difficulties at age 81 months (odds ratio = 0.86, 95% confidence interval: 0.79, 0.95) and was similarly associated with hyperactivity and conduct problems. Evidence was weak for an association between birth length and behavioral problems earlier in childhood. In summary, there was a weak association between intrauterine growth restriction, indexed by birth length (rather than weight), and childhood behavioral problems. Future work should focus on elucidating the biologic mechanisms that lead to variations in birth length and underlie this association.

Heterogeneity in Assessing Self-Reports of Caffeine Exposure

Article

Mar 2002
EPIDEMIOLOGY

Background. Coffee and its metabolite caffeine are widely studied for their health effects but with inconclusive results. Caffeine is particularly difficult to assess, and therefore we explore heterogeneity of caffeine exposure. Methods. We categorized caffeine exposure among 2,478 pregnant women in southern New England during 1996–2000 by the traditional laboratory-based methods of M. Bunker and M. McWilliams. A subsample was examined to ascertain caffeine levels of brewed or purchased beverages actually consumed. Results. More than half (56.6%) of women drank coffee since becoming pregnant. Serving sizes ranged from 2 to 32 oz and are considerably larger than laboratory standards, which are typically 8–10 oz, as compared with the standard of 5 to 6 oz. Conversely, caffeine content per serving of coffee was one-third the laboratory standard, eg, 100 mg caffeine compared with 300 mg for a 10-oz cup. Tea brewed more than 3 minutes contained 42 mg caffeine as compared with the standard of 94 mg. When the amount of caffeine actually consumed was measured, one-quarter (24.8%) of subjects traditionally classified as consuming 300+ gm caffeine daily were reclassified as consuming 150–299 mg. Conclusion. Misclassification of caffeine consumption increases difficulty in identifying health effects from caffeine. Some combination of more precise consumption data and a biomarker such as paraxanthine may more precisely estimate exposure.

Bias in parental reports? Maternal psychopathology and the reporting of problem behavior in clinic-referred children

Article

Sep 2003

In clinical practice, child psychologists' case formulations are often based on parental reports. In this study, we examined whether mothers' reports of internalizing and externalizing behavior problems in their children might be biased by maternal psychopathology. The target child sample consisted of 68 boys aged 6-12 years who were receiving treatment. Mothers' reports were compared with the reports of both teachers and group care workers as criterion ratings. After controlling for variance shared with the independent raters, multiple regression analysis indicated substantial partial correlations between various types of maternal psychopathology and the reporting of internalizing child behavior problems. Only small to insignificant partial correlations were found in the case of externalizing behavior problems. This finding is consistent with the social attribution theory that predicts greater distortion when observing more ambiguous stimuli. (PsycINFO Database Record (c) 2012 APA, all rights reserved)

Demographic and perinatal factors for behavioral problems among children aged 4-9 in Taiwan: Regular article

Article

May 2009
PSYCHIAT CLIN NEUROS

Aim: To investigate the effects of age, gender, prenatal/perinatal factors, and maternal psychological distress on childhood emotional/behavioral problems, and the gender difference in the patterns of comorbid emotional/behavioral problems. Methods: The sample included 1391 children aged 4–9 in Taipei using a multi-stage sampling method. Their mothers completed questionnaires including demographics, prenatal/perinatal variables, the Child Behavior Checklist, and the Chinese Health Questionnaire. The linear and non-linear mixed model was used for data analysis. Results: Boys scored higher on externalizing problems, and girls scored higher on internalizing problems. Gender also modified the comorbid patterns of emotional/behavioral problems. Aggressive behaviors decreased, but attention and thought problems increased with age. Prenatal/perinatal exposure to alcohol and coffee, vaginal bleeding, and gestational diabetes, low birthweight, and postnatal incubation and resuscitation, and maternal psychological distress predicted the risk for several childhood emotional/behavioral problems. Conclusion: Prenatal/perinatal and maternal care, and gender-specific measures are important for prevention of childhood emotional/behavioral problems.

Neonatal correlates of prenatal exposure to smoking, caffeine, and alcohol

Article

Jul 1984
INFANT BEHAV DEV

Effects of prenatal exposure to smoking and caffeine were studied in 173 new-borns whose mothers consumed little or no alcohol during pregnancy. Measures of the three substances consumed before and during pregnancy were derived from a maternal interview. Infant outcome measures included birth size, gestational age, and behavior based on the Neonatal Behavioral Assessment Scale (Brazelton, 1973). Smoking during pregnancy was related to: smaller birth size and less irritability; caffeine, to shorter gestation and poorer neuromuscular development and reflex functioning; and alcohol, to greater placidity. Ingestion of caffeine prior to pregnancy predicted poorer orientation and greater arousal and irritability, even when levels of caffeine consumption during pregnancy were held constant. These findings were not attributable to a variety of other potential confounds, such as demographic background, stress, obstetrical medication, or other substances ingested during pregnancy. While the behavioral effects of smoking were mediated by birth size, intrauterine exposure to alcohol and caffeine predicted behavioral effects that were independent of physical or gestational age deficits.

Potential teratogenic and neurodevelopmental consequences of coffee and caffeine exposure: A review on human and animal data

Article

Nov 1994
NEUROTOXICOL TERATOL

The teratogenic effect of caffeine has been clearly demonstrated in rodents. The sensitivity of different animals species is variable. Malformations have been demonstrated in mice at 50–75 mg/kg of caffeine, whereas the lowest dose usually needed to induce malformations is 80 mg/kg in rats. However, when caffeine is administered in fractioned amounts during the day, 330 mg/kg/day are necessary to reach teratogenicity in rats. In rodents, the most frequently observed malformations are those of the limbs and digits, ectrodactyly, craniofacial malformations (labial and palatal clefts) and delays in ossification of limbs, jaw and sternum. Nevertheless, even in rodents, caffeine can be considered as a weak teratogenic agent, given the quite large quantities of caffeine necessary to induce malformations and the small number of animals affected. In humans, caffeine does not present any teratogenic risk. The increased risk of the most common congenital malformations entailed by moderate consumption of caffeine is very slight. However, caffeine potentiates the teratogenic effect of other substances, such as tobacco, alcohol, and acts synergistically with ergotamine and propranolol to induce materno-fetal vasoconstrictions leading to malformations induced by ischemia. Therefore, even though caffeine does not seem to be harmful to the human fetus when intake is moderate and spread out over the day, some associations, especially with alcohol, tobacco, and vasoconstrictive or anti-migraine medications should be avoided.Maternal consumption of caffeine affects brain composition, especially in case of a low-protein diet and also seems to interfere with zinc fixation in brain. Maternal exposure to caffeine induces also long-term consequences on sleep, locomotion, learning abilities, emotivity, and anxiety in rat offspring, whereas in humans, more studies are needed to ascertain long-term behavioral effects of caffeine ingestion by pregnant mothers.

Adenosine, energy metabolism and sleep homeostasis

Article

Oct 2010

Adenosine is directly linked to the energy metabolism of cells. In the central nervous system (CNS) an increase in neuronal activity enhances energy consumption as well as extracellular adenosine concentrations. In most brain areas high extracellular adenosine concentrations, through A1 adenosine receptors, decrease neuronal activity and thus the need for energy. Adenosine may be a final common pathway for various sleep factors. We have identified a relatively specific area, the basal forebrain (BF), which appears to be central in the regulation/execution of recovery sleep after sleep deprivation (SD), or prolonged wakefulness. Adenosine concentration increases in this area during SD, and this increase induces sleep while prevention of the increase during SD abolishes recovery sleep. The increase in adenosine is associated with local changes in energy metabolism as indicated by increases in levels of pyruvate and lactate and increased phosphorylation of AMP-activated protein kinase. The increases in adenosine and sleep are associated with intact cholinergic system since specific lesion of the BF cholinergic cells abolishes both. Whether adenosine during SD is produced by the cholinergic neurons or astrocytes associated with them remains to be explored. An interesting, but so far unexplored question regards the relationship between the local, cortical regulation of sleep homeostasis and the global regulation of the state of sleep as executed by lower brain mechanisms, including the BF. The increase in adenosine concentration during SD also in cortical areas suggests that adenosine may have a role in the local regulation of sleep homeostasis. The core of sleep need is probably related to primitive functions of life, like energy metabolism. It can be noted that this assumption in no way excludes the possibility that later in evolution additional functions may have developed, e.g., related to complex neuronal network functions like memory and learning.

A review of the epidemiologic evidence concerning the reproductive health effects of caffeine consumption: A 2000-2009 update

Article

Oct 2010

This review of human studies of caffeine and reproductive health published between January 2000 and December 2009 serves to update the comprehensive review published by Leviton and Cowan (2002). The adverse reproductive outcomes addressed in this review include: (1) measures of subfecundity; (2) spontaneous abortion; (3) fetal death; (4) preterm birth; (5) congenital malformations; and (6) fetal growth restriction. Methodologic challenges and considerations relevant to investigations of each reproductive endpoint are summarized, followed by a brief critical review of each study. The evidence for an effect of caffeine on reproductive health and fetal development is limited by the inability to rule out plausible alternative explanations for the observed associations, namely confounding by pregnancy symptoms and smoking, and by exposure measurement error. Because of these limitations, the weight of evidence does not support a positive relationship between caffeine consumption and adverse reproductive or perinatal outcomes.

Maternal caffeine intake from coffee and tea, fetal growth, and the risks of adverse birth outcomes: The Generation R Study

Article

Jun 2010
AM J CLIN NUTR

Caffeine is a widely used and accepted pharmacologically active substance. The effect of caffeine intake during pregnancy on fetal growth and development is still unclear. We examined the associations of maternal caffeine intake, on the basis of coffee and tea consumption, with fetal growth characteristics measured in each trimester of pregnancy and the risks of adverse birth outcomes. Associations were studied in 7346 pregnant women participating in a population-based prospective cohort study from early pregnancy onward in the Netherlands (2001-2005). Caffeine intake in the first, second, and third trimesters was on the basis of coffee and tea consumption and was assessed by questionnaires. Fetal growth characteristics were repeatedly measured by ultrasound. Information about birth outcomes was obtained from hospital records. We observed no consistent associations of caffeine intake with fetal head circumference or estimated fetal weight in any trimester. Higher caffeine intake was associated with smaller first-trimester crown-rump length, second- and third-trimester femur length, and birth length (P for trend <0.05). Offspring of mothers who consumed > or =6 caffeine units/d tended to have increased risks of small-for-gestational-age infants at birth. Our results suggest that caffeine intake of > or =6 units/d during pregnancy is associated with impaired fetal length growth. Caffeine exposure might preferentially adversely affect fetal skeletal growth. Further studies are needed to assess these associations in non-European populations and to assess the postnatal consequences.

Intrauterine exposure to caffeine and inattention/overactivity in children: Caffeine and inattention/overactivity

Article

Mar 2010
ACTA PAEDIATR

To determine the association between intrauterine exposure to timing and sources of caffeine and inattention/overactivity, suggesting ADHD in the child. This study used prospectively collected data from the large population-based study, The Norwegian Mother and Child Cohort Study (MoBa). Participants were 25 343 mothers and their 18-month-old children. Mothers reported on consumption of a number of caffeine sources at the 17th week and 30th week of gestation, as well as child inattention/overactivity at 18 months. Data were analysed using univariate analyses of covariance (ancova). Once we controlled for confounders, there was a small effect of caffeine intake at 17th week of gestation on inattention/overactivity combined, and both 17th and 30th week of gestation on overactivity, when investigated separately from inattention. Surprisingly, the caffeine effect was only found for soft drinks, not tea or coffee. Intrauterine exposure to soft drinks rather than coffee, the traditional focus, is associated with maternal reports of overactive behaviour in children aged 18 months.

New Dutch reference curves for birthweight by gestational age

Article

Nov 2009

To construct new Dutch reference curves for birthweight by parity, sex and ethnic background. Retrospective nationwide study. Reference curves for birthweight were constructed using the LMS model and were based on 176,000 singleton births in the Netherlands in the year 2001 (approximately 95% of all births in that year). Separate birthweight curves were constructed for male and female babies born from primiparous and multiparous women from 25 to 43 weeks gestational age. The reference curves are similar to the Swedish references. Birthweight at early gestation was lower than in the previous Dutch reference curves and higher from term onwards. Infants of Hindustani women had a significantly lower birthweight, so that a separate reference curve was constructed. The new Dutch reference curves show a different pattern than the Dutch reference curves collected more than 50 years ago, reflecting changes in prenatal conditions and care.

Maternal caffeine consumption and risk of neural tube defects

Article

Nov 2009
BIRTH DEFECTS RES A

Animal studies demonstrate teratogenic effects of caffeine, whereas human studies are inconclusive. Associations between maternal caffeine consumption and neural tube defects (NTDs) by type of NTD (anencephaly, spina bifida, or encephalocele) were examined using data from the National Birth Defects Prevention Study (NBDPS). Total average daily caffeine from coffee, tea, soda, and chocolate consumption during the year before pregnancy was estimated for 768 mothers of infants with NTDs and 4143 mothers of infants without birth defects who gave birth during 1997 through 2002. Periconceptional use of caffeine-containing medications was evaluated separately. Adjusted odds ratios (OR) and 95% confidence intervals (CI) associated with consumption of total caffeine and each caffeine source were estimated from logistic regression models. Positive associations were observed between spina bifida and total caffeine consumption (OR 1.4; 95% CI: 1.1-1.9) and each caffeine source except caffeinated tea, which showed a negative association with spina bifida (OR 0.7; 95% CI: 0.6-0.9). Associations with modestly increased risk of NTDs and encephalocele were also observed. The association between caffeine consumption and anencephaly differed by maternal race/ethnicity. No dose effects were found. Additional studies should confirm whether women who consume caffeine are at increased risk for pregnancies complicated by NTDs.

Chronic Prenatal Caffeine Exposure Impairs Novel Object Recognition and Radial Arm Maze Behaviors in Adult Rats

Article

Sep 2009

In this report, we demonstrate that chronic prenatal exposure to a moderate dose of caffeine disrupts novel object recognition and radial arm maze behaviors in adult male and female rats. Pregnant dams were administered either tap water or 75 mg/L caffeinated tap water throughout gestation. Oral self-administration in the drinking water led to an approximate maternal intake of 10mg/kg/day, equivalent to 2-3 cups of coffee/day in humans based on a metabolic body weight conversion. In adulthood, the offspring underwent testing on novel object recognition, radial arm maze, and Morris water maze tasks. Prenatal caffeine exposure was found to impair 24-h memory retention in the novel object recognition task and impair both working and reference memory in the radial arm maze. However, prenatal caffeine exposure did not alter Morris water maze performance in either a simple water maze procedure or in an advanced water maze procedure that included reversal and working memory paradigms. These findings demonstrate that chronic oral intake of caffeine throughout gestation can alter adult cognitive behaviors in rats.

Coffee consumption during pregnancy and the risk of hyperkinetic disorder and ADHD: A prospective cohort study

Article

Oct 2008
ACTA PAEDIATR

Based on hypotheses from experimental studies, we studied the association between intrauterine exposure to coffee and the risk of clinically verified hyperkinetic disorder and attention-deficit hyperactivity disorder (ADHD). A cohort study with prospectively collected data from the Aarhus Birth Cohort, Denmark. We included 24 068 singletons delivered between 1990 and 1998. Linkage was performed with three Danish longitudinal registers: The Danish Psychiatric Central Register, The Integrated Database for Labour Market Research and The Danish Civil Registration System. We identified 88 children with hyperkinetic disorder and ADHD. Information about coffee consumption during pregnancy was obtained at 16 weeks of gestation from self-administrated questionnaires. Potential confounding factors were evaluated using Cox regression analyses. We found that intrauterine exposure to 10 or more cups of coffee per day was associated with a threefold increased risk of hyperkinetic disorder and ADHD. After adjustments for a number of confounding factors, the risk decreased and became statistically insignificant (RR 2.3, 95% CI 0.9-5.9). Prenatal exposure to high levels of coffee did not significantly increase the risk of clinically verified hyperkinetic disorder and ADHD in childhood.

Behavioral effects of exposure to caffeine during gestation, lactation or both

Article

Nov 1991
NEUROTOXICOL TERATOL

Open-field behavior and latencies of emergence from a darkened chamber to a brightly lit arena were recorded at 1, 2, 4 and 6 months after birth in male and female rats that had been exposed to 26 or 45 mg/kg/day caffeine ingested by dams in their drinking water during gestation, 25 or 35 mg/kg/day during lactation or to the two low or high doses ingested during both gestation and lactation. One or both of the gestational or lactational doses reduced locomotor activity and increased defecation in the open field at all ages for males only. Rearing was decreased for both sexes by 25 mg/kg/day lactational caffeine. Numbers of rats that failed to or took longer than 1 min to emerge into the brightly lit arena were increased by 26 mg/kg/day gestational caffeine. All rats that had been exposed to either dose combination of caffeine during both gestation and lactation showed less locomotor and rearing activity, reduced tendencies to emerge within 1 min and, at 6 months of age only, more defecation in the open field. It was concluded that the effects of gestational and lactational exposure to caffeine were additive in their modification of the developing brain as reflected in decreased motor activity possibly arising from heightened emotional reactivity to the testing situation. Hypersensitivity of males to caffeine exposure during either gestation or lactation separately seemed to diminish when exposure was increased for all rats through experience of the drug during both gestation and lactation. Possible involvement of caffeine-induced increases in adenosine receptors in the type of results obtained was discussed.

Lasting effects of early chronic caffeine feeding on rats' behavior and brain in later life

Article

May 1991
PHYSIOL BEHAV

Pregnant dams were fed a 20% protein diet with caffeine (2 mg/100 g b.wt.), starting on day 9 of gestation. At birth, each dam with 8 assigned pups was fed this diet until weaning, day 22. On day 22, female rats were caged and fed this diet until day 93. Starting on day 93, the caffeine-supplemented diet was replaced with a caffeine-free, 20% protein diet until day 388. Starting on day 31, each animal was placed in a photoactivity cage, and locomotive activity was measured until day 375. On day 388, the animals were killed, and their brains were removed and divided into 7 regions. The weight, DNA, protein and zinc contents, and alkaline phosphatase activity of each region were determined. Locomotive activity of the caffeine-fed group was higher than in the noncaffeine control group. Accumulative activity scores showed 3 subgroups (high, medium, and low) in both groups at day 93. The medium activity subgroup in the caffeine group was greater than the controls from day 72 to day 93. These differences reappeared 5 weeks after cessation of caffeine supplementation and continued until day 375. The differences in activity were minimum in the high and low subgroups. Chronic caffeine intake in early life permanently affected the medium activity subgroup. Furthermore, various regions of the brain were biochemically altered in spite of the feeding of a noncaffeine diet for almost 300 days after caffeine.

Caffeine use during pregnancy and child outcome: A 7-year prospective study

Article

Jul 1991
NEUROTOXICOL TERATOL

Caffeine (from coffee, tea, cola, and/or chocolate) was the most frequently ingested drug among 1529 pregnant women interviewed in 1974-75. Linear and threshold effects of prenatal caffeine on pregnancy outcome and offspring development were examined in a cohort of approximately 500 offspring. After appropriate statistical adjustment for relevant covariates (cigarette smoking, alcohol, maternal size, demographics, etc.) prenatal caffeine exposure was not related to most newborn and infant outcome measures, including height, weight or head circumference, or to individually administered IQ and attention tests at 7 years of age. Only one isolated dependent variable of the many was significantly associated with prenatal caffeine exposure: namely breech presentation. However, since this report involved a secondary analysis of data gathered for other purposes, specifically designed studies would be required to determine the validity of the observed association for any particular variable. The general conclusion is that the long-term consequences of prenatal caffeine in this cohort are null.

Neurobehavioral Effects of Prenatal Caffeine

Article

Feb 1989

Thomas J. Sobotka

Behavioral effects of prenatal exposure to caffeine in rats

Article

Apr 1986
LIFE SCI

For the first ten days of gestation, rats received daily intraperitoneal injections of 10-40 mg/kg of caffeine. Open field behavior of their fostered offspring was observed 61, 145 and 188 days after birth. While there were no obvious physical effects of the prenatal experience, at 61 days caffeine exposure led to an increase in the number of times seen walking for males only and increased ambulation (distance travelled) for both sexes. At 145 days occupancy of centre squares of the apparatus and latencies of emergence from a dark box into an illuminated arena were higher for caffeine-exposed males only. When 188 days old, rats exposed to 20 mg/kg of caffeine tended to exhibit less locomotor activity and more grooming behavior while spending more time in corners of the apparatus. Male rats prenatally exposed to 20 mg/kg of caffeine avoided the centre squares of the apparatus. It was concluded that prenatal caffeine had modified the development of mechanisms controlling voluntary motor activity in the youngest rats. However, at older ages, the prenatal effect was probably manifested as increased timidity or emotional reactivity. Males were often affected differently from females by the prenatal treatment.

Adverse effect of maternal caffeine ingestion on fetal cerebrum in rat

Article

Feb 1983
BRAIN DEV-JPN

This study was undertaken to determine whether maternal caffeine ingestion is or is not a risk factor in fetal cerebral development using experimental rat models. Pregnant rats of the Wistar strain were given 0.04% caffeine in drinking water before and/or during pregnancy for various numbers of days. Control rats received water for the same periods. There was no reduction of maternal body weight, fetal body weight or fetal total brain weight. Low fetal cerebral weight and placental weight were observed when dams were given caffeine before mating for long times and/or throughout pregnancy. DNA, RNA and protein contents per cerebrum were also reduced in fetuses from dams given caffeine throughout pregnancy or for the last 6 gestational days. Cerebral DNA and protein contents as expressed per wet weight were higher and significantly lower respectively in the fetuses from dams given caffeine throughout pregnancy when compared to controls. Activity of thymidine kinase was not significantly decreased in caffeine-treated fetuses. There was a positive correlation between maternal serum and fetal cerebral caffeine levels. Additionally a negative correlation between maternal caffeine levels and fetal survival rates which decreased in litters from dams given caffeine throughout pregnancy was demonstrated. Our rat model indicates maternal caffeine ingestion during pregnancy is associated with reduction of fetal cerebral weight and protein content without reduction of body weight.

Caffeine Intake During Pregnancy and Risk of Problem Behavior in 5- to 6-Year-Old Children

Abstract

No full-text available