Meta-analysis of epigenome-wide associations between DNA methylation at birth and childhood cognitive skills.

Cognitive skills are a strong predictor of a wide range of later life outcomes. Genetic and epigenetic associations across the genome explain some of the variation in general cognitive abilities in the general population and it is plausible that epigenetic associations might arise from prenatal environmental exposures and/or genetic variation early in life. We investigated the association between cord blood DNA methylation at birth and cognitive skills assessed in children from eight pregnancy cohorts within the Pregnancy And Childhood Epigenetics (PACE) Consortium across overall (total N = 2196), verbal (total N = 2206) and non-verbal cognitive scores (total N = 3300). The associations at single CpG sites were weak for all of the cognitive domains investigated. One region near DUSP22 on chromosome 6 was associated with non-verbal cognition in a model adjusted for maternal IQ. We conclude that there is little evidence to support the idea that variation in cord blood DNA methylation at single CpG sites is associated with cognitive skills and further studies are needed to confirm the association at DUSP22.

Developmental trajectories of motor skills during the preschool period.

Children with developmental coordination disorder also manifest difficulties in non-motor domains (attentional, emotional, behavioral and socialization skills). Longitudinal studies can help disentangle the complex relationships between the development of motor skills and other cognitive domains. This study aims to examine the contribution of early cognitive factors to changes in motor skills during the preschool period. Children (N = 1144) from the EDEN mother-child cohort were assessed for motor skills with the Copy Design task (NEPSY battery) and the parent-rated Ages and Stages Questionnaire (fine and gross motor skills scores) at ages 3 and 5-6 years. At 3 years, language skills were evaluated using tests from the NEPSY and ELOLA batteries. Emotional problems, conduct problems, inattention and hyperactivity symptoms, peer relationships and pro-social behavior were assessed with the Strengths and Difficulties Questionnaire (SDQ) also at 3 years. Linear and logistic regression models were performed to examine whether positive and negative changes in motor skills between 3 and 5-6 years are associated with specific cognitive skills at 3 years, while adjusting for a broad range of pre- and postnatal environmental factors. In the linear regression model, the SDQ Inattention symptoms score at 3 years was associated with negative changes in motor skills (standardized ß = - 0.09, SD = 0.03, p value = 0.007) and language skills at 3 years were associated with positive changes in motor skills (standardized ß = 0.05, SD = 0.02, p value = 0.041) during the preschool period. In logistic regression models, the SDQ Inattention symptoms score at 3 years was associated with a higher likelihood of a declining trajectory of motor skills (OR [95% CI] = 1.37 [1.02-1.84]). A higher language skills score at 3 years was associated with an increased likelihood of a resilient trajectory (1.67 [1.17-2.39]). This study provides a better understanding of the natural history of developmental coordination delays by identifying cognitive factors that predict changes in motor skills between the ages of 3 and 5-6 years.

Breastfeeding, Polyunsaturated Fatty Acid Levels in Colostrum and Child Intelligence Quotient at Age 5-6 Years.

OBJECTIVE: To examine the relationship of polyunsaturated fatty acid (PUFA) in breast milk with children's IQ. STUDY DESIGN: In the French Etude des Déterminants pré- et postnatals précoces du développement et de la santé de l'Enfant (EDEN) mother-child cohort, colostrum samples were collected at the maternity unit. Colostrum omega-6 and omega-3 PUFA were analyzed by gas chromatography. At age 5-6 years, the IQs of 1080 children were assessed using the Wechsler Preschool and Primary Scale of Intelligence-III. The relationships of breastfeeding duration and PUFA levels with children's IQs were examined by linear regression. RESULTS: Full scale IQ of ever breastfed children was 4.5 (95% CI: 2.7, 6.2) higher than never breastfed children in the unadjusted model, but this was not statistically significant in the adjusted model (1.3 points higher [-0.4, 3.0]). Any breastfeeding duration was associated with full scale (0.20 [0.00, 0.41] points/month) and verbal (0.31 [0.09, 0.52]) IQ. Colostrum linoleic acid (LA) levels were negatively associated with Verbal IQ (-0.6 [-1.1, 0.0] points per 1% level increase). Children exposed to colostrum high in LA and low in docosahexaenoic acid (DHA) had lower IQs than those exposed to colostrum high in DHA (3.0 [0.5, 5.5] points) and those exposed to colostrum low in LA and DHA (4.4 [1.6, 7.3] points). Finally, the association between breastfeeding duration and child IQ was stronger when LA levels were high. CONCLUSIONS: Duration of breastfeeding and colostrum PUFA levels were associated with children's IQs in the EDEN cohort. These data support breastfeeding and add evidence for the role of early PUFA exposure on childhood cognition.

Persistent maternal depressive symptoms trajectories influence children's IQ: The EDEN mother-child cohort.

BACKGROUND: This study assessed the association between timing and course of maternal depression from pregnancy onwards and children's cognitive development at ages 5 to 6. Potential interaction effects with child sex and family socioeconomic status were explored. METHODS: One thousand thirty-nine mother-child pairs from the French EDEN mother-child birth cohort were followed from 24 to 28 weeks of pregnancy onwards. Based on Center for Epidemiological Studies Depression (CES-D) and Edinburgh Postnatal Depression Scale (EPDS) scores assessed at six timepoints, longitudinal maternal depressive symptom trajectories were calculated with a group-based semiparametric method. Children's cognitive function was assessed at ages 5 to 6 by trained interviewers with the Wechsler Preschool and Primary Scale of Intelligence Third Edition (WPPSI-III), resulting in three composite scores: Verbal IQ (VIQ), Performance IQ (PIQ), and Full-Scale IQ (FSIQ). RESULTS: Five trajectories of maternal symptoms of depression could be distinguished: no symptoms, persistent intermediate-level depressive symptoms, persistent high depressive symptoms, high symptoms in pregnancy only, and high symptoms in the child's preschool period only. Multiple linear regression analyses showed that, compared to children of mothers who were never depressed, children of mothers with persistent high levels of depressive symptoms had reduced VIQ, PIQ, and FSIQ scores. This association was moderated by the child's sex, boys appearing especially vulnerable in case of persistent maternal depression. CONCLUSIONS: Chronicity of maternal depression predicts children's cognitive development at school entry age, particularly in boys. As maternal mental health is an early modifiable influence on child development, addressing the treatment needs of depressed mothers may help reduce the associated burden on the next generation.

The association between linoleic acid levels in colostrum and child cognition at 2 and 3 y in the EDEN cohort.

BACKGROUND: Breastfeeding has been associated with improved cognitive development. This may be explained by polyunsaturated fatty acid (PUFA) content of breast milk, especially long-chain (LC) PUFA that are needed for postnatal brain growth. METHODS: Using data from the French EDEN cohort, we aimed to study whether the PUFA content of colostrum may explain observed associations between breastfeeding duration and cognitive scores at 2 and 3 y. A total of 709 breastfed children with available data on PUFA composition of milk were assessed using parent-reported questionnaires for motor and language at 2 y of age, or global cognition at 3 y. Multiple linear regressions were used to examine associations between PUFA levels and child cognitive scores, after controlling for many confounders. RESULTS: We found no association between LCPUFA levels in colostrum and child development. However, levels of linoleic acid (LA) were negatively associated with motor and cognitive scores, independently of breastfeeding duration. Children breastfed with the highest levels of LA tended to score closer to the never breastfed children than children breastfed with the lowest levels of LA. CONCLUSION: Our findings suggest that too high levels of LA in colostrum are associated with poorer child development at 2 and 3 y.

Air pollution during pregnancy and childhood cognitive and psychomotor development: six European birth cohorts.

BACKGROUND: Accumulating evidence from laboratory animal and human studies suggests that air pollution exposure during pregnancy affects cognitive and psychomotor development in childhood. METHODS: We analyzed data from 6 European population-based birth cohorts-GENERATION R (The Netherlands), DUISBURG (Germany), EDEN (France), GASPII (Italy), RHEA (Greece), and INMA (Spain)-that recruited mother-infant pairs from 1997 to 2008. Air pollution levels-nitrogen oxides (NO2, NOx) in all regions and particulate matter (PM) with diameters of <2.5, <10, and 2.5-10 µm (PM2.5, PM10, and PMcoarse, respectively) and PM2.5 absorbance in a subgroup-at birth addresses were estimated by land-use regression models, based on monitoring campaigns performed primarily between 2008 and 2011. Levels were back-extrapolated to exact pregnancy periods using background monitoring sites. Cognitive and psychomotor development was assessed between 1 and 6 years of age. Adjusted region-specific effect estimates were combined using random-effects meta-analysis. RESULTS: A total of 9482 children were included. Air pollution exposure during pregnancy, particularly NO2, was associated with reduced psychomotor development (global psychomotor development score decreased by 0.68 points [95% confidence interval = -1.25 to -0.11] per increase of 10 µg/m in NO2). Similar trends were observed in most regions. No associations were found between any air pollutant and cognitive development. CONCLUSIONS: Air pollution exposure during pregnancy, particularly NO2 (for which motorized traffic is a major source), was associated with delayed psychomotor development during childhood. Due to the widespread nature of air pollution exposure, the public health impact of the small changes observed at an individual level could be considerable.

Breastfeeding duration and cognitive development at 2 and 3 years of age in the EDEN mother-child cohort.

OBJECTIVE: To investigate the dose-response relationship between breastfeeding duration and cognitive development in French preschool children. STUDY DESIGN: In the French EDEN Mother-Child Cohort Study, we evaluated language ability with the Communicative Development Inventory (CDI) in 1387 2-year-old children and overall development with the Ages and Stages Questionnaire (ASQ) in 1199 3-year-old children. Assessments were compared between breastfed and non-breastfed children and also according to breastfeeding duration in multivariable linear models, controlling for a wide range of potential confounders. We tested departure from linearity. RESULTS: After adjustments, ever-breastfed children scored 3.7 ± 1.8 (P = .038) points higher than never-breastfed children on the CDI and 6.2 ± 1.9 (P = .001) points higher on the ASQ. Among breastfed children, exclusive and any-breastfeeding durations were positively associated with both CDI and ASQ scores. The fine motor domain of ASQ was associated with any-breastfeeding duration, and the problem solving domain with exclusive-breastfeeding duration. We did not observe significant departures from linearity. No interactions were found between the child's sex, parental education or socioeconomic status, and breastfeeding duration. CONCLUSION: Longer breastfeeding duration was associated with better cognitive and motor development in 2- and 3-year-old children and a dose-response relationship was suggested.

The dietary n6:n3 fatty acid ratio during pregnancy is inversely associated with child neurodevelopment in the EDEN mother-child cohort.

Long-chain polyunsaturated fatty acids (LC-PUFAs) of the n6 (ω6) and n3 series are essential for the development of a child's brain. Fetal LC-PUFA exposure as well as infant exposure via breast milk depend on the maternal intake of these LC-PUFAs and of their respective dietary precursors (PUFAs). We aimed to investigate the associations between maternal LC-PUFA and PUFA [(LC)PUFA] dietary intake during pregnancy and child neurodevelopment at ages 2 and 3 y. In 1335 mother-child pairs from the EDEN cohort, we evaluated associations between daily maternal (LC)PUFA intake during the last 3 months of pregnancy with the child's language at age 2 y and with different assessments of development at age 3 y. Associations were investigated separately in breastfed and never-breastfed children. We examined interactions between the ratios of n6 and n3 (LC)PUFA intakes (n6:n3 fatty acid ratio) and duration of breastfeeding. Breastfeeding mothers had a lower n6:n3 fatty acid ratio (8.4 vs. 8.8; P = 0.02). Among never-breastfed children (n = 338), we found negative associations between maternal dietary n6:n3 fatty acid ratios and neurodevelopment, as reflected by the child's language at age 2 y (ß ± SE = -2.1 ± 0.7; P = 0.001) and development assessed with the Ages and Stages Questionnaire at age 3 y (-1.5 ± 0.8; P = 0.05). Among mothers with a high n6:n3 fatty acid ratio only, breastfeeding duration was positively associated with language at age 2 y (P-interaction < 0.05). This suggests that the ratio between maternal dietary n6 and n3 (LC)PUFA intake possibly influences the child's brain development during fetal life but not during or by breastfeeding. However, breastfeeding might compensate for prenatal imbalance in maternal dietary n6:n3 fatty acid ratio.

Emergency tracheal intubation of severely head-injured children: changing daily practice after implementation of national guidelines.

OBJECTIVE: To report daily practice of scene emergency tracheal intubation performed by physicians and changes induced by implementation of national guidelines, with special attention to rapid sequence induction (RSI) and control of assisted ventilation. DESIGN: Observational study. SETTING: Pediatric intensive care unit of a university hospital. PATIENTS: A total of 296 children (age, 2-15 yrs old) referred to our center for severe traumatic brain injury (Glasgow Coma Scale score of ≤ 8), with spontaneous cardiac rhythm. INTERVENTIONS: Scene RSI practice by field physicians was compared before (n = 188), and after (n = 108) publication of national guidelines. Emergency tracheal intubation conditions, RSI use, immediate complications, assisted ventilation efficiency on blood gases measurements upon arrival, and, in the later period, physician's knowledge, and observance to published guidelines were analyzed. MEASUREMENTS AND MAIN RESULTS: After publication of guidelines, tracheal intubation was performed at the scene in 100% of the cases (vs. 88%, p = .05); RSI practice was more standardized, with an increased use of succinylcholine (10% to 80%, p = .0001), and a concomitant decreased use of nondepolarizing muscle relaxant (20% vs. 0%, p = .005), and opioids (70% vs. 36%, p = .05). Recommended RSI protocol (etomidate and succinylcholine) was effectively used by 64% of the physicians (vs. 2.8%, p = .001), and rate of immediate complications upon tube insertion (mainly cough reflex) decreased to 8% (vs. 25%, p = .0015). Scene emergency tracheal intubation, when ordered, resulted in a 100% success rate and adequate oxygenation within the two groups. Despite increasing the use of portable capnograph in the later period, Paco2 was measured outside the tight target range (35-40 torr, 4.6-5.3 kPa) in 70% of the cases upon arrival. CONCLUSIONS: Scene emergency tracheal intubation was effectively performed by trained careproviders in children with traumatic brain injury. Implementation of guidelines led to a more standardized practice of RSI, decreased rate of immediate complications, but insufficient control of Paco2 during transport.

Is Handedness at Five Associated with Prenatal Factors?

The goal of the study was to investigate some of the factors suspected to be related to children's handedness: presentation during the last weeks of gestation and at birth (cephalic or breech), side of presentation (right or left), number of weeks of gestation, season of birth, parents' handedness and sex. We analyzed the relationships between these factors and the child's handedness at five years. Children (n = 1897) from the EDEN cohort participated in the study, among which 1129 were tested for handedness at five. The father's handedness, but not the mother's, was significantly related to the child's hand preference. The percentage of left-handed children was significantly larger when the father was non-right-handed compared to right-handed, and tended to be larger among children in non-left-cephalic presentation compared to left-cephalic presentation. Girls, but not boys, were significantly less lateralized when they were born before 37 weeks of pregnancy than after. Finally, children born in winter or spring were slightly but significantly less lateralized than children born in summer or autumn. All six children who were not lateralized at 5 presented one or several of these factors. These results are discussed in light of the mixed model of handedness.

Exposure to screens and children's language development in the EDEN mother-child cohort.

Studies in children have reported associations of screen time and background TV on language skills as measured by their parents. However, few large, longitudinal studies have examined language skills assessed by trained psychologists, which is less prone to social desirability. We assessed screen time and exposure to TV during family meals at ages 2, 3 and 5-6 years in 1562 children from the French EDEN cohort. Language skills were evaluated by parents at 2 years (Communicative Development Inventory, CDI) and by trained psychologists at 3 (NEPSY and ELOLA batteries) and 5-6 years (verbal IQ). Cross-sectional and longitudinal associations were assessed by linear regression adjusted for important confounders. Overall, daily screen time was not associated with language scores, except in cross-sectional at age 2 years, where higher CDI scores were observed for intermediate screen time. Exposure to TV during family meals was consistently associated with lower language scores: TV always on (vs never) at age 2 years was associated with lower verbal IQ (- 3.2 [95% IC: - 6.0, - 0.3] points), independent of daily screen time and baseline language score. In conclusion, public health policies should better account for the context of screen watching, not only its amount.

Executive function after severe childhood traumatic brain injury - Age-at-injury vulnerability periods: The TGE prospective longitudinal study.

BACKGROUND: Executive function (EF) impairment is a major predictor of overall outcome after traumatic brain injury (TBI). TBI severity is a factor of poor outcome, but most studies include a majority of children with mild and moderate TBI. The aims of this study were to estimate EF impairment after severe childhood TBI and to explore factors predicting EF outcome. The secondary aim was to compare recovery trajectories by age-at-injury groups. METHODS: This was a prospective longitudinal study of children with severe TBI who were tested for EFs by performance-based tests and questionnaires at 3, 12 and 24 months. RESULTS: Children with TBI (n=65) showed significant impairment in working memory, inhibition, attention and global EF, with little or no recovery at 24 months. For flexibility and performance-based EF score, children were impaired at 3 months only and showed normal scores by 12 months. No impairment was found in planning. At 3 and 24 months, Glasgow Coma Scale score and parental education predicted global EF. Coma length was not a significant predictor of outcome. Age at injury predicted progress in EF, but the relationship was not linear; children 10-12 years old at injury showed better outcome than older and younger children. CONCLUSIONS: EFs are impaired after severe TBI in childhood. The relationship between age at injury and outcome is not linear. Relying on only performance-based EF tests can underestimate EF impairment.

Prenatal Exposure to Nonpersistent Endocrine Disruptors and Behavior in Boys at 3 and 5 Years.

BACKGROUND: Sex-specific associations have been reported between phthalates, bisphenol A (BPA), and child behavior. No data on large study populations are available for other phenols with possible endocrine-disrupting properties. OBJECTIVES: We aimed to study associations between prenatal exposure to phthalates and several phenols on behavior among male infants. METHODS: We quantified 11 phthalate metabolites and nine phenols (four parabens, benzophenone-3, BPA, two dichlorophenols, triclosan) in spot urine samples collected during pregnancy among EDEN cohort mothers who delivered a boy. Mothers completed the Strength and Difficulties Questionnaire (SDQ) when their children were 3.1 (n=529) and 5.6 (n=464) y old. RESULTS: BPA was positively associated with the relationship problems subscale at 3 y [incidence rate ratio (IRR): 1.11; 95% confidence interval (CI): 1.03, 1.20] and the hyperactivity-inattention subscale scores at 5 y (IRR: 1.08; 95% CI: 1.01, 1.14). Mono-n-butyl phthalate (MnBP) was positively associated with internalizing behavior, relationship problem, and emotional symptom scores at 3 y. Monobenzyl phthalate (MBzP) was positively associated with internalizing behavior and relationship problems scores at 3 y. After dichotomizing SDQ scores, triclosan tended to be positively associated with emotional symptom subscales at both 3 and 5 y. CONCLUSIONS: The observed associations between BPA, MnBP, and behavior in boys are consistent with previous findings. Further health impact assessment studies based on dose-response functions corrected for exposure misclassification are required to quantify the public health burden possibly entailed by such associations. https://doi.org/10.1289/EHP1314.

Social Withdrawal Behaviour at One Year of Age Is Associated with Delays in Reaching Language Milestones in the EDEN Mother-Child Cohort Study.

OBJECTIVE: The aim of the study was to examine the relationship between social withdrawal behaviour at one year and motor and language milestones. MATERIALS AND METHODS: One-year old children from the EDEN French population-based birth cohort study (Study on the pre- and postnatal determinants of the child's development and prospective health Birth Cohort Study) were included. Social withdrawal at one year was assessed by trained midwives using the Alarm Distress BaBy (ADBB) scale. Midwives concurrently examined infants' motor and language milestones. Parents reported on child's psychomotor and language milestones, during the interview with the midwife. RESULTS: After adjusting for potential confounding factors, social withdrawal behaviour was significantly associated with concurrent delays in motor and language milestones assessed by the midwife or the parents. DISCUSSION: Higher scores on social withdrawal behaviour as assessed with the ADBB were associated with delays in reaching language milestones, and to a lesser extent with lower motor ability scores. Taking the contribution of social withdrawal behaviour into account may help understand the unfolding of developmental difficulties in children.

Prenatal Caffeine Exposure and Child IQ at Age 5.5 Years: The EDEN Mother-Child Cohort.

BACKGROUND: Evidence from animal studies suggests maternal caffeine intake during pregnancy has detrimental effects on subsequent brain development in offspring. However, human data in this area are limited. The aim of this study was to assess whether caffeine intake by women during pregnancy is associated with impaired cognitive development in offspring at age 5.5 years. METHODS: Multivariate modeling was conducted using data of 1083 mother-child pairs from a population-based birth cohort in France followed from pregnancy to age 5.5 years of the children. Measures included an estimate of maternal caffeine intake during pregnancy, children's IQ at age 5.5, and individual and family characteristics. RESULTS: Prenatal caffeine exposure was common in the sample (91%) with 12% displaying an intake ≥200 mg/day (high). Multivariable modeling showed a significant negative relationship between caffeine intake and children's IQ at 5.5 years (-.94 [95% confidence interval = -1.70, -.17] full IQ unit per 100 mg daily caffeine intake). In particular, children of mothers consuming ≥200 mg/day were more likely to have borderline or lower IQ compared with children of mothers consuming <100 mg/day (13.5% vs. 7.3%; odds ratio = 2.30, 95% confidence interval = 1.13, 4.69). CONCLUSIONS: We found an association between caffeine intake during pregnancy and impaired cognitive development in offspring, a result in line with animal data. More epidemiologic and biologically grounded research is needed to determine whether this association is causal. This finding suggests that conservative guidelines regarding the maximum caffeine intake recommended in pregnancy (i.e., 200 mg/day) should be maintained.

Predicting changes in language skills between 2 and 3 years in the EDEN mother-child cohort.

Objective. To examine the factors predicting changes in language skills between 2 and 3 years. Methods. By using longitudinal data concerning 1002 children from the EDEN study, linear regression was used to predict 3-year language performance from 2-year language performance and the risk factors associated with language delays. Logistic regressions were performed to examine two change trajectories: children who fall below the 10th percentile of language skills between 2 and 3 years (declining trajectory), and those who rose above the 10th percentile (resilient trajectory). Results. The final linear model accounted for 43% of the variance in 3-year language scores, with 2-year language scores accounting for 22%. Exposure to alcohol during pregnancy, earlier birth term, lower level of parental education and lower frequency of maternal stimulation were associated with the declining trajectory. Breastfeeding was associated with the resilient trajectory. Conclusions. This study provides a better understanding of the natural history of early language delays by identifying biological and social factors that predict changes in language skills between the ages of 2 and 3 years.

Assessment of visuo-attentional abilities in young children with or without visual disorder: toward a systematic screening in the general population.

In young children, visual attention, analysis or memory is only rarely evaluated. Moreover, tools to test for such higher-order visual capacities in children are limited. In an attempt to develop and refine such tools, we selected nine tests to assess visuo-attentional abilities before formal reading education (grade 1). The battery consisted of gaze fixation, visual field, visual extinction, binocular visual pursuit, visual memory, "A" cancellation, Teddy bears cancellation, embedded figures, and matching tasks. This battery was used in the general population (n=110) to calculate cut-off scores identifying the lower 5% of the general population to obtain a screening measure for neurovisual disabilities in children. To evaluate our battery's sensitivity and specificity to neurovisual disorders over ophthalmological diseases, a neurovisual group (n=9) and an ophthalmologic group (n=13) also completed the tests. Overall, all but three tests of the battery could be used to discriminate between neurovisual and ophthalmologic children. The ophthalmologic children failed the visual field extent examination and the cancellation tasks, consistent with deleterious effects of ophthalmologic disease on visual perception as well as higher-order vision. Using the cut-off scores, the battery identified only 2 out of 13 ophthalmologic patients, but 5 out of 9 neurovisual patients. In the general population, these cut-off scores identified seven children. These children were previously undiagnosed with any disability (i.e., no diagnosis of ophthalmological, neurological, or psychiatric disease) and thus did not receive any rehabilitation. This preliminary study highlights the necessity for a neurovisual disorder screening tool for young children.

Egocentric reference in bidirectional readers as measured by the straight-ahead pointing task.

The present study aimed to show that bidirectional reading and language exposure influence the position of egocentric reference (ER), the perceived direction of the body's sagittal axis proposed to act as an anchor for movements in extracorporeal space. Directional factors (e.g., visual scanning bias and reading habits) have been proposed to influence visuospatial performance, such as in line bisection and figure drawing. In past studies, bidirectional readers have been less consistent in demonstrating a bias compared to unidirectional readers. Using a straight-ahead pointing task to assess egocentric reference, we compared 14 unidirectional left-to-right readers (Uni-LR) to three bidirectional reading groups that differed in the reading direction of their native language and/or the level of their second language literacy: 16 low-English literate, native right-to-left, bidirectional readers (Lo-Bi-RL), 13 high-English literate, native right-to-left, bidirectional readers (Hi-Bi-RL), and 15 native left-to-right, bidirectional readers (Bi-LR). Participants were asked to point straight-ahead while blindfolded using either a left-to-right or a right-to-left scanning direction to approach the subjective sagittal midline. Uni-LRs showed left-side spatial bias when scanning left-to-right and right-side bias during right-to-left scanning, Bi-LRs and Lo-Bi-RLs (i.e., intermediate level or less in their second language) demonstrated the opposite pattern, and Hi-Bi-RLs showed left-side spatial bias regardless of scanning direction. Results are discussed in terms of accuracy and spatial bias regarding the interaction between reading direction and spatial cognition based on the level of bidirectional literacy and language exposure.