Birth Cohort Study Research Articles

Risk of Major Congenital Malformations Associated with the Use of Japanese Traditional (Kampo) Medicine Containing Ephedra During the First Trimester of Pregnancy.

Japanese traditional (Kampo) medicines containing ephedra may be used to treat colds during pregnancy. There are reports that ephedrine, a component of ephedra, has a risk of teratogenicity; however, the evidence remains equivocal. This study aimed to evaluate the risk of major congenital malformations (MCMs) associated with exposure to Kampo medicines containing ephedra during the first trimester of pregnancy using the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study). To 23,730 mother-infant pairs who participated in the TMM BirThree Cohort Study from July 2013 to March 2017, questionnaires in early and middle pregnancy were distributed approximately at weeks 12 and 26 of pregnancy, respectively. Infants' risk of MCMs in women who used Kampo medicines containing ephedra or acetaminophen during the first trimester was assessed, and the odds ratios (ORs) were estimated with unadjusted and adjusted analyses. Among 20,879 women, acetaminophen and Kampo medicines containing ephedra were used in 665 (3.19%) and 376 (1.80%) women, respectively, in the first trimester. Among the infants born to the mothers who used acetaminophen or Kampo medicine containing ephedra during the first trimester, 11 (1.65%) and 8 (2.13%), respectively, had overall MCMs. OR of overall MCMs was higher in women who used Kampo medicines containing ephedra than in those who used acetaminophen in the first trimester (adjusted OR, 1.45; 95% confidence interval (CIs), 0.57-3.71); however, the difference was not statistically significant. In this study, there was no statistically significant association between the use of Kampo medicines containing ephedra during the first trimester of pregnancy and the risk of MCMs. Although some point estimates of ORs exceeded 1.00, the absolute magnitude of any increased risks would be low.

Associations between prenatal metal exposure and growth rate in children: Based on Hangzhou Birth Cohort Study

BackgroundIt has been reported that prenatal metal exposure is associated with child anthropometry. However, studies focusing on the growth rate of anthropometry among children have not been conducted. This study aimed to examine associations between the exposure of multiple metals during pregnancy and the growth rate of anthropometry among offspring. Methods743 mother-child pairs from the Hangzhou Birth Cohort Study (HBCS) were included. Levels of eleven metals in mother's blood during pregnancy were measured. Offspring had a mean of 5.7 measurements on anthropometric indicators including weight, length/height, head circumference, and body mass index (BMI) within 1.5 years of birth. Generalized estimating equation (GEE) model was used to investigate the associations between maternal metal exposure and growth rate of anthropometric indicators in children. Stratification analysis by sex was also examined. ResultsLevels of selenium (Se, β = 0.213, 95 % CI = 0.017 to 0.409, P = 0.033) were positively associated with length/height gain per month in children. Levels of chromium (Cr, β = 0.025, 95 % CI = 0.018 to 0.033, P < 0.001) were positively associated with the rate of weight gain. Levels of manganese (Mn, β = −0.030, 95 % CI = −0.052 to −0.008, P = 0.009) and cobalt (Co, β = −0.012, 95 % CI = −0.024 to −0.000, P = 0.044) were inversely associated with growth rate of head circumference. Children with higher maternal Mn levels had a lower BMI change rate. Associations between metals and growth rate were stronger in girls than in boys. Besides, significant associations between metal mixtures and growth rate were found. ConclusionPrenatal exposure to Se, Cr, Mn, and Co was associated with growth rate in children, with sex-specific disparities. Our results suggested important effects of maternal exposure to multiple metals on development in offspring.

Risk and rates of hospitalisation in young children: A prospective study of a South African birth cohort.

Children in sub-Saharan Africa (SSA) are disproportionately affected by morbidity and mortality. There is also a growing vulnerable population of children who are HIV-exposed uninfected (HEU). Understanding reasons and risk factors for early-life child hospitalisation will help optimise interventions to improve health outcomes. We investigated hospitalisations from birth to two years in a South African birth cohort study. Mother-child pairs in the Drakenstein Child Health Study were followed from birth to two years with active surveillance for hospital admission and investigation of aetiology and outcome. Incidence, duration, cause, and factors associated with child hospitalisation were investigated, and compared between HEU and HIV-unexposed uninfected (HUU) children. Of 1136 children (247 HEU; 889 HUU), 314 (28%) children were hospitalised in 430 episodes despite >98% childhood vaccination coverage. The highest hospitalisation rate was from 0-6 months, decreasing thereafter; 20% (84/430) of hospitalisations occurred in neonates at birth. Amongst hospitalisations subsequent to discharge after birth, 83% (288/346) had an infectious cause; lower respiratory tract infection (LRTI) was the most common cause (49%;169/346) with respiratory syncytial virus (RSV) responsible for 31% of LRTIs; from 0-6 months, RSV-LRTI accounted for 22% (36/164) of all-cause hospitalisations. HIV exposure was associated with increased incidence rates of hospitalisation in infants (IRR 1.63 [95% CI 1.29-2.05]) and longer hospital admission (p = 0.004). Prematurity (HR 2.82 [95% CI 2.28-3.49]), delayed infant vaccinations (HR 1.43 [95% CI 1.12-1.82]), or raised maternal HIV viral load in HEU infants were risk factors for hospitalisation; breastfeeding was protective (HR 0.69 [95% CI 0.53-0.90]). In conclusion, children in SSA experience high rates of hospitalisation in early life. Infectious causes, especially RSV-LRTI, underly most hospital admissions. HEU children are at greater risk of hospitalisation in infancy compared to HUU children. Available strategies such as promoting breastfeeding, timely vaccination, and optimising antenatal maternal HIV care should be strengthened. New interventions to prevent RSV may have additional impact in reducing hospitalisation.

Lifespan adversities affect neural correlates of behavioral inhibition in adults.

Growing evidence suggests that adverse experiences have long-term effects on executive functioning and underlying neural circuits. Previous work has identified functional abnormalities during inhibitory control in frontal brain regions in individuals exposed to adversities. However, these findings were mostly limited to specific adversity types such as maltreatment and prenatal substance abuse. We used data from a longitudinal birth cohort study (n = 121, 70 females) to investigate the association between adversities and brain responses during inhibitory control. At the age of 33 years, all participants completed a stop-signal task during fMRI and an Adult Self-Report scale. We collected seven prenatal and postnatal adversity measures across development and performed a principal component analysis to capture common variations across those adversities, which resulted in a three-factor solution. Multiple regression analysis was performed to identify links between adversities and brain responses during inhibitory control using the identified adversity factors to show the common effect and single adversity measures to show the specific contribution of each adversity. To find neural correlates of current psychopathology during inhibitory control, we performed additional regression analyses using Adult Self-Report subscales. The first adversity factor reflecting prenatal maternal smoking and postnatal psychosocial adversities was related to higher activation during inhibitory control in bilateral inferior frontal gyri, insula, anterior cingulate cortex, and middle temporal gyri. Similar results were found for the specific contribution of the adversities linked to the first adversity factor. In contrast, we did not identify any significant association between brain responses during inhibitory control and the second adversity factor reflecting prenatal maternal stress and obstetric risk or the third adversity factor reflecting lower maternal sensitivity. Higher current depressive symptoms were associated with higher activation in the bilateral insula and anterior cingulate cortex during inhibitory control. Our findings extended previous work and showed that early adverse experiences have a long-term effect on the neural circuitry of inhibitory control in adulthood. Furthermore, the overlap between neural correlates of adversity and depressive symptomatology suggests that adverse experiences might increase vulnerability via neural alterations, which needs to be investigated by future longitudinal research.

Profiles and transplacental transfer of per- and polyfluoroalkyl substances in maternal and umbilical cord blood: A birth cohort study in Zhoushan, Zhejiang Province, China

Per- and polyfluoroalkyl substances (PFAS) can pass through the placental barrier and pose health risks to fetuses. However, exposure and transplacental transfer patterns of emerging PFAS remain unclear. Here, 24 PFAS were measured in paired maternal whole blood (n = 228), umbilical cord whole blood (n = 119) and serum (n = 120). Orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to differentiate PFAS between different matrices. The transplacental transfer (TPT) of PFAS was calculated using cord to maternal whole blood concentration ratios. PFOS and PFOA were still the dominant PFAS in maternal samples. The emerging PFAS had higher TPT than PFOS and PFOA. Moreover, PFAS with the same chain length but different functional groups and C-F bonds showed different TPT, such as PFOS and PFOSA (C8, median: 0.090 vs. 0.305, p < 0.05) and PFHxS and 4:2 FTS (C6, median: 0.220 vs. 1.190, p < 0.05). A significant sex difference in 4:2 FTS (median: boys 1.250, girls 1.010, p < 0.05) were found. Furthermore, we observed a significant U-shaped trend for the TPT of carboxylates with increasing carbon chain length. PFAS showed a compound-specific transfer through placental barrier and a compound-specific distribution between different matrices in this study.

Association of allergies in children younger than 3 years with levels of maternal intake of n-3 polyunsaturated fatty acids or fish during pregnancy: A nationwide birth cohort study, the Japan Environment and Children's Study

BackgroundN-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties and are expected to prevent the onset of allergies. However, epidemiological studies investigating the relationship between child allergies and maternal intake of n-3 PUFAs or fish have yielded inconsistent results. MethodsFollowing exclusions from a dataset comprising 103,057 records from the Japan Environment and Children's Study, 72,105 participants were divided into five groups according to mothers' intake of n-3 PUFAs or fish during pregnancy to assess the risk of their children being diagnosed with allergy by 3 years old. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for child allergies were calculated using multivariable logistic regression analyses with reference to the lowest intake group. ResultsLevels of maternal intake of n-3 PUFAs or fish showed inverted associations (i.e., reduced risk) with the incidence of physician-diagnosed allergic rhinoconjunctivitis or parent-reported symptoms of current rhinitis with eye symptoms at different time points and the cumulative incidence from birth to 3 years of age. Inverted associations were also found for current wheeze at 1-<2 years of age and current eczema at 1-<2 and 0-<3 years of age. However, for food allergies, no significant associations were observed in the incidence in each group compared with the lowest intake group at any age. ConclusionsThe findings suggest that n-3 PUFA intake during pregnancy may reduce the risk of developing allergic diseases and symptoms in children. In addition, consumption of n-3 PUFAs or fish is very unlikely to increase the risk of allergy given that the results are from a country with high fish consumption. Trial registration: UMIN000030786 https://rctportal.niph.go.jp/detail/um?trial_id=UMIN000030786.

The association between gestational weight trajectories in women with gestational diabetes and their offspring's weight from birth to 40 months

AimsTo identify the gestational weight gain (GWG) patterns in women with gestational diabetes mellitus (GDM) and evaluate their association with offspring weight status from birth to 40 months.Materials and methodsThis study included 2,723 GDM-mother–child pairs from the Beijing Birth Cohort Study. The association between GWG trajectories identified by the latent class model and offspring weight outcomes from birth to 40 months were evaluated, after adjustment for maternal age, parity, pre-pregnancy body mass index, maternal height, and blood glucose levels.ResultsThree GWG rate groups, including the non-excessive GWG group (1,994/2,732), excessive GWG group (598 /2,732), and excessive early GWG group (140/2,732), were identified in women with GDM, respectively. Compared to the non-excessive GWG group, the adjusted OR (aOR) and 95% CI were 1.83 (1.35–2.47) and 1.79 (1.06–3.01) for macrosomia, 1.33 (1.07–1.66) and 1.48 (1.01–2.17) for large for gestational age (LGA) in the excessive GWG group and excessive early GWG group. Excessive GWG was also associated with an increased risk of BMI-for-age at 40 months (aOR = 1.66, 95% CI 1.14–2.42).ConclusionsBoth excessive GWG and excessive early GWG increased the risk of macrosomia and LGA in women with GDM, but only the excessive GWG was associated with childhood overweight/obesity. The results suggest the long-term impact of GWG on offspring weight status in women with GDM and the potential benefits of GWG restriction after GDM diagnosis.

Harmonisation of assessments of attention, social, emotional, and behaviour problems using the Child Behavior Checklist and the Strengths and Difficulties Questionnaire

AbstractObjectivesRetrospective harmonisation of data obtained through different instruments creates measurement error, even if the underlying concepts are assumed the same. We tested a novel method for item‐level data harmonisation of two widely used instruments that measure emotional and behavioural problems: the Child Behavior Checklist (CBCL) and the Strengths and Difficulties Questionnaire (SDQ).MethodsItem content of the CBCL and SDQ was mapped onto four dimensions: emotional problems, peer relationship problems, hyperactivity/inattention and conduct problems. A diverse test sample was drawn from four prospective longitudinal birth cohort studies in Australia and Europe who used one or both instruments. The pooled sample included 5188 data points assessing children and adolescents aged 6–13 years (N = 257–704 participants per cohort). Measurement invariance was assessed using latent variable multi‐group confirmatory factor analysis.ResultsFifteen items from the CBCL and SDQ were mapped onto four dimensions allowing for measurement invariance testing as part of a stepwise process. Partial strict invariance between CBCL and SDQ assessments was established for all four dimensions.ConclusionsThe harmonised dimensions of emotional, peer relationship, hyperactivity/inattention and conduct problems are invariant across the CBCL and SDQ suggesting that these dimensions can be reliably compared with limited measurement error.

Prenatal Exposure to Bisphenols and Visual Impairment in Preschool Children: A Prospective Birth Cohort Study in China

Prenatal Exposure to Bisphenols and Visual Impairment in Preschool Children: A Prospective Birth Cohort Study in China

Early life stress in relation with risk of overweight, depression, and their comorbidity across adulthood: findings from a British birth cohort.

Multimorbidity, known as the co-occurrence of at least two chronic conditions, has become of increasing concern in the current context of ageing populations, though it affects all ages. Early life risk factors of multimorbidity include adverse childhood experiences (ACEs), particularly associated with psychological conditions and weight problems. Few studies have considered related mechanisms and focus on old age participants. We are interested in estimating, from young adulthood, the risk of overweight-depression comorbidity related to ACEs while adjusting for early life confounders and intermediate variables. We used data from the 1958 National Child Development Study, a prospective birth cohort study (N = 18 558). A four-category outcome (no condition, overweight only, depression only and, overweight-depression comorbidity) was constructed at 23, 33, and 42 years. Multinomial logistic regression models adjusting for intermediate variables co-occurring with this outcome were created. ACEs and sex interaction on comorbidity risk was tested. In our study sample (N = 7762), we found that ACEs were associated with overweight-depression comorbidity risk throughout adulthood (RRR [95% CI] at 23y = 3.80 [2.10-6.88]) though less overtime. Comorbidity risk was larger than risk of separate conditions. Intermediate variables explained part of the association. After full-adjustment, an association remained (RRR [95% CI] at 23y = 2.00 [1.08-3.72]). Comorbidity risk related to ACEs differed by sex at 42. Our study provides evidence on the link and potential mechanisms between ACEs and the co-occurrence of mental and physical diseases throughout the life-course. We suggest addressing ACEs in intervention strategies and public policies to go beyond single disease prevention.

How do schools influence the emotional and behavioural health of their pupils? A multi-level analysis of 135 schools in the Born in Bradford inner city multi-ethnic birth cohort

PurposeTo estimate variation in emotional and behavioural problems between primary schools in Bradford, an ethnically diverse and relatively deprived city in the UK.MethodsWe did a cross-sectional analysis of data collected from 2017 to 2021 as part of the ‘Born In Bradford’ birth cohort study. We used multilevel linear regression in which the dependent variable was the Strengths and Difficulties Questionnaire (SDQ) total score, with a random intercept for schools. We adjusted for pupil-level characteristics including age, ethnicity, socioeconomic status, and parental mental health.ResultsThe study included 5,036 participants from 135 schools. Participants were aged 7–11 years and 56% were of Pakistani heritage. The mean SDQ score was 8.84 out of a maximum 40. We estimated that the standard deviation in school-level scores was 1.41 (95% CI 1.11–1.74) and 5.49% (95% CI 3.19–9.37%) of variation was explained at school level. After adjusting for pupil characteristics, the standard deviation of school-level scores was 1.04 (95% CI 0.76–1.32) and 3.51% (95% CI 1.75–6.18%) of variation was explained at school level. Simulation suggested that a primary school with 396 pupils at the middle of the distribution has 63 pupils (95% CI 49–78) with a ‘raised’ SDQ score of 15 + /40; and shifting a school from the lower to the upper quartile would prevent 26 cases (95% CI 5–46).ConclusionThe prevalence of emotional and behavioural problems varies between schools. This is partially explained by pupil characteristics; though residual variation in adjusted scores may suggest that schools have a differential impact on mental wellbeing.

Structural Relationships between Asthma and Dental Caries in Children: A Birth Cohort Study in Southern Brazil

Introduction: There is an inconclusive causal association between asthma symptoms and dental caries in the primary dentition. This study aimed to investigate, using SEM (structural equation modeling), a possible causal relation between asthma and dental caries in the primary dentition. Methods: Using data from the 2004 Pelotas Birth Cohort Study, a sub-sample of 1,303 individuals was selected. Dental caries was clinically evaluated at 5 years old based on decayed, missing, and filled tooth (dmft) index criteria. Asthma-related symptoms (wheezing and shortness of breath) at 1- and 4-year-olds composed a latent variable and were the main exposures to caries occurrence. SEM was used to identify possible direct, indirect, and mediated effects of asthma in primary dentition dental caries. Results: The general prevalence of caries at age 5 was 1.95 (SD: 3.56). When comparing the dmft values for children with asthma symptoms and those without, they presented similar values in both periods where asthma symptoms were evaluated (1- and 4-year-old). SEM analysis showed that asthma was neither directly nor indirectly related to dental caries. Conclusion: Asthma, using a latent variable constructed based on asthma symptoms, showed no causal effect on dental caries occurrence in the primary dentition.

Associations of socioeconomic and lifestyle characteristics, psychological symptoms, multimorbidity, and multisite pain with sciatica – a 15-year longitudinal study

Sciatica is defined as pain radiating from the low back to the leg, usually below the knee. It is a disabling condition that causes a major burden to health care and society. Previous evidence of the multifactorial etiology of sciatica comes mostly from cross-sectional studies. Larger, longitudinal studies with a multidimensional set of variables are needed. To examine how socioeconomic and lifestyle characteristics, psychological symptoms, multimorbidity, and multisite pain are associated with sciatica. A longitudinal study of the Northern Finland Birth Cohort 1966. In total 6,683 working-aged members of the Northern Finland Birth Cohort 1966. Self-reported sciatic pain status over a 15-year study period. We conducted a 15-year longitudinal study from the age of 31 to 46. We used multivariable generalized estimation equations analysis to examine how socioeconomic characteristics (low education, unemployment, and living alone), lifestyle characteristics (overweight, obesity, current smoking, and physical inactivity), psychological symptoms (depression, anxiety), multimorbidity, and multisite pain were associated with sciatica. At the age of 31, 21.1% of the study population reported sciatic pain and at the age of 46, 36.7%. Multisite pain was clearly the strongest factor associated with sciatica (odds ratio [OR] 2.61, 95% confidence interval [CI] 2.34‒2.92). In descending order of effect size, older age, low education, psychological symptoms, multimorbidity, overweight, obesity, physical inactivity and current smoking were positively associated with sciatica. Their ORs varied between 1.17 and 2.18. Living alone was negatively associated with sciatica (OR 0.81, 95% CI 0.72‒0.90). Multisite pain had the strongest association with sciatica. The effect sizes of the other factors were clearly smaller. To our knowledge this is the first study to evaluate the association of multisite pain with sciatica. This finding may have considerable implications for clinical work treating patients with sciatica.

Cord blood lipid correlation network profiles are associated with subsequent attention-deficit/hyperactivity disorder and autism spectrum disorder symptoms at 2 years: a prospective birth cohort study

BackgroundAttention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are neurodevelopmental conditions with early life origins. Alterations in blood lipids have been linked to ADHD and ASD; however, prospective early life data are limited. This study examined (i) associations between the cord blood lipidome and ADHD/ASD symptoms at 2 years of age, (ii) associations between prenatal and perinatal predictors of ADHD/ASD symptoms and cord blood lipidome, and (iii) mediation by the cord blood lipidome. MethodsFrom the Barwon Infant Study cohort (1074 mother-child pairs, 52.3% male children), child circulating lipid levels at birth were analysed using ultra-high-performance liquid chromatography-tandem mass spectrometry. These were clustered into lipid network modules via Weighted Gene Correlation Network Analysis. Associations between lipid modules and ADHD/ASD symptoms at 2 years, assessed with the Child Behavior Checklist, were explored via linear regression analyses. Mediation analysis identified indirect effects of prenatal and perinatal risk factors on ADHD/ASD symptoms through lipid modules. FindingsThe acylcarnitine lipid module is associated with both ADHD and ASD symptoms at 2 years of age. Risk factors of these outcomes such as low income, Apgar score, and maternal inflammation were partly mediated by higher birth acylcarnitine levels. Other cord blood lipid profiles were also associated with ADHD and ASD symptoms. InterpretationThis study highlights that elevated cord blood birth acylcarnitine levels, either directly or as a possible marker of disrupted cell energy metabolism, are on the causal pathway of prenatal and perinatal risk factors for ADHD and ASD symptoms in early life. FundingThe foundational work and infrastructure for the BIS was sponsored by the Murdoch Children's Research Institute, Deakin University, and Barwon Health. Subsequent funding was secured from the Minderoo Foundation, the European Union's Horizon 2020 research and innovation programme (ENDpoiNTs: No 825759), National Health and Medical Research Council of Australia (NHMRC) and Agency for Science, Technology and Research Singapore [APP1149047], The William and Vera Ellen Houston Memorial Trust Fund (via HOMER Hack), The Shepherd Foundation, The Jack Brockhoff Foundation, the Scobie & Claire McKinnon Trust, the Shane O'Brien Memorial Asthma Foundation, the Our Women Our Children's Fund Raising Committee Barwon Health, the Rotary Club of Geelong, the Ilhan Food Allergy Foundation, Geelong Medical and Hospital Benefits Association, Vanguard Investments Australia Ltd, the Percy Baxter Charitable Trust, and Perpetual Trustees.

Discrepancy between Caregivers’ Reports and Physicians’ Evaluation of Causative Foods in Food Protein-Induced Enterocolitis Syndrome in Japan: The Japan Environment and Children’s Study

Introduction: Food protein-induced enterocolitis syndrome (FPIES) is a form of non-IgE-mediated gastrointestinal food allergy. FPIES is considered a rare food allergy disorder and is often under-recognized. Therefore, clinicians should have a better understanding of its manifestations and maintain a high index of suspicion for a correct diagnosis. To this end, information about differences in the characteristics of caregiver-reported and physician-diagnosed FPIES is important. Methods: The present, national, multicentric, prospective birth cohort study, called the Japan Environment and Children’s Study (JECS), enrolled a general population of 104,062 fetal records. The characteristics of FPIES in 1.5-year-old children were categorized as cases reported by caregivers or as those diagnosed by a physician using questionnaire data. Results: The prevalence of caregiver-reported and physician-diagnosed FPIES cases was 0.69% and 0.06%, respectively. Among the former, the most common causative food was hen’s egg (HE), and the second most common causative food was cow’s milk (CM) (51.0% and 17.1% of patients responded to HE and CM, which accounted for 46% and 15% of all the causative foods, respectively). Conversely, among the physician-diagnosed cases, the most common causative food was CM followed by HE (57.7% and 36.5% of patients responded to CM and HE, which accounted for 46% and 29% of all the causative foods, respectively). CM accounted for a significantly higher proportion of causative foods in physician-diagnosed FPIES while HE accounted for a significantly higher proportion of caregiver-reported FPIES (p < 0.05). Conclusion: A discrepancy was found in reports of the most common causative food between caregiver-reported and physician-diagnosed cases of FPIES.

Accelerometer-based sleep metrics and gut microbiota during adolescence: Association findings from a Brazilian population-based birth cohort

BackgroundSleep and gut microbiota are emerging putative risk factors for several physical, mental, and cognitive conditions. Sleep deprivation has been shown to be linked with unhealthy microbiome environments in animal studies. However, in humans, the results are mixed. Epidemiological studies evaluating the effect of accelerometer-based sleep measures on gut microbiome are scarce. This study aims to explore the relationship between sleep duration and efficiency with the gut microbiota in adolescence. MethodsA subsample of 352 participants from the 2004 Pelotas (Brazil) Birth Cohort Study with sleep and fecal microbiota data available were included in the study. Sleep duration and sleep efficiency were obtained from actigraphy information at 11 years old whereas microbiota information from fecal samples was collected at 12 years. The fecal microbiota was analyzed via Illumina MiSeq (16S rRNA V3–V4 region) and the UNOISE pipeline. Alpha was assessed in QIIME2. Association measures for sleep variables and microbial α-diversity, and bacterial relative abundance were assessed through generalized models (linear and logistic regression), adjusting for maternal and child variables confounders. ResultsAdjusted models showed that sleep duration was positively associated with Simpson index of α-diversity (β = 0.003; CI95 %: 0.00004; 0.01). Both sleep duration (OR = 0.43; CI95 % 0.25; 0.74) and efficiency (OR = 0.55; CI95 % 0.38; 0.78) were associated with lower Bacteroidetes abundance. ConclusionOur results suggest that sleep duration and efficiency are linked to gut microbiota diversity and composition even with 1–2 years gap from exposure to outcome. The findings support the role of sleep in the gut-brain axis as well as provide insights on how to improve microbiota health.

The Population-Attributable Fractions of Small-for-Gestational-Age Births: Results from the Japan Birth Cohort Consortium.

A fetal growth restriction is related to adverse child outcomes. We investigated risk ratios and population-attributable fractions (PAF) of small-for-gestational-age (SGA) infants in the Japanese population. Among 28,838 infants from five ongoing prospective birth cohort studies under the Japan Birth Cohort Consortium, two-stage individual-participant data meta-analyses were conducted to calculate risk ratios and PAFs for SGA in advanced maternal age, pre-pregnancy underweight, and smoking and alcohol consumption during pregnancy. Risk ratio was calculated using modified Poisson analyses with robust variance and PAF was calculated in each cohort, following common analyses protocols. Then, results from each cohort study were combined by meta-analyses using random-effects models to obtain the overall estimate for the Japanese population. In this meta-analysis, an increased risk (risk ratio, [95% confidence interval of SGA]) was significantly associated with pre-pregnancy underweight (1.72 [1.42-2.09]), gestational weight gain (1.95 [1.61-2.38]), and continued smoking during pregnancy (1.59 [1.01-2.50]). PAF of underweight, inadequate gestational weight gain, and continued smoking during pregnancy was 10.0% [4.6-15.1%], 31.4% [22.1-39.6%], and 3.2% [-4.8-10.5%], respectively. In conclusion, maternal weight status was a major contributor to SGA births in Japan. Improving maternal weight status should be prioritized to prevent fetal growth restriction.

Prenatal paternal anxiety symptoms predict child DHEA levels and internalizing symptoms during adrenarche.

This study examined (1) whether measures of paternal anxious and depressive symptoms collected prenatally and during a follow-up assessment when the child was in middle childhood, predict child neuroendocrine outcomes, and (2) whether neuroendocrine outcomes are intermediate factors between paternal mental health and child cognitive/behavioral outcomes. Middle childhood coincides with increased autonomy as the child transitions into grade school, and with adrenarche, as the maturing adrenal gland increases secretion of dehydroepiandrosterone (DHEA) and its sulfated metabolite (DHEA-S), hormones that are implicated in corticolimbic development which regulate emotions and cognition. Participants were recruited from a subsample of a large prospective birth cohort study (3D study). We conducted a follow-up study when children were 6-8 years old (N = 61 families, 36 boys, 25 girls). Parental symptoms of anxiety, stress and depression were assessed via validated self-report questionnaires: prenatally using an in-house anxiety questionnaire, the Perceived Stress Scale (PSS) and the Center for Epidemiologic Studies Depression (CES-D), and at the follow up, using the Beck Anxiety and Beck Depression Inventories. Children provided salivary hormone samples, and their pituitary gland volume was measured from structural Magnetic Resonance Imaging (MRI) scans. Child behaviors were measured using the Strengths and Difficulties Questionnaire and cognitive outcomes using the WISC-V. Multiple regression analyses were used to test whether paternal mental health symptoms assessed prenatally and during childhood are associated with child neuroendocrine outcomes, adjusting for maternal mental health and child sex. Indirect-effect models assessed whether neuroendocrine factors are important intermediates that link paternal mental health and cognitive/behavioral outcomes. (1) Fathers' prenatal anxiety symptoms predicted lower DHEA levels in the children, but not pituitary volume. (2) Higher prenatal paternal anxiety symptoms predicted higher child internalizing symptoms via an indirect pathway of lower child DHEA. No associations were detected between paternal anxiety symptoms measured in childhood, and neuroendocrine outcomes. No child sex differences were detected on any measure. These results highlight the often-overlooked role of paternal factors during pregnancy on child development, suggesting that paternal prenatal anxiety symptoms are associated with child neuroendocrine function and in turn internalizing symptoms that manifest at least up to middle childhood.

Exposure to Residential Green Space and Bone Mineral Density in Young Children

Bone mass accrual is influenced by environmental and lifestyle factors. Targeted interventions at the early stages of life might decrease fracture and/or osteoporosis risk later in life. To investigate whether early-life exposure to residential surrounding green space is associated with a change in bone mineral density in young children. In this prospective birth cohort study (ENVIRONAGE [Environmental Influence on Aging in Early Life]), mother-child pairs from Flanders, Belgium, were recruited at birth and followed up for 4 to 6 years, between October 1, 2014, and July 31, 2021. Data analysis was conducted between January and February 2022. Green space was estimated for high green (>3 m vegetation height), low green (≤3 m vegetation height ), and total green (sum of high and low) within several radii (100-3000 m) around the residence after geocoding of the addresses. Radial bone mineral density was assessed using quantitative ultrasound measurement at follow-up, measured as the mean of the axially transmitted speed of sound in meters per second. Multiple linear and logistic regression models were used while accounting for relevant covariates and potential confounders. The study population comprised 327 children (180 [55.0%] female; mean [SD] age, 4.6 [0.4] years at the follow-up evaluation). Early-life exposure to residential green space was associated with increased childhood bone health. An IQR increment in total green (21.2%) and high green (19.9%) space within 500 m was associated with an increase of 27.38 m/s (95% CI, 9.63-45.13 m/s) and 25.30 m/s (95% CI, 7.93-42.68 m/s) in bone mineral density, respectively. Additionally, an IQR increase in total (25.2%) and high (23.2%) green space within 1000 m was associated with a 67% (odds ratio, 0.33; 95% CI, 0.17-0.61) and 61% (odds ratio, 0.39; 95% CI, 0.18-0.75) lower risk of having a bone density lower than the sex-specific 10th percentile (3567.6 m/s for girls and 3522.8 m/s for boys). In this study of children aged 4 to 6 years, higher bone mineral density and a lower risk of having low bone density were associated with higher residential green space exposure during childhood. These findings highlight the importance of early-life exposure to residential green space on bone health during critical periods of growth and development, with long-term implications.

Trajectories of maternal depressive and anxiety symptoms and child's socio-emotional outcome during early childhood

Maternal symptoms of depression and anxiety during pregnancy and early postnatal years are suggested to impose differential negative effects on child's socio-emotional development depending on the characteristics of the symptoms, such as timing, intensity, and persistence. The aim of this study was to identify trajectories of maternal depressive and anxiety symptoms from pregnancy until 2 years postpartum and to examine their relationship with child socio-emotional problems and competence at 2 and 5 years of age.The sample included 1208 mother-infant dyads from FinnBrain Birth Cohort study. Latent growth mixture modelling (LGMM) was utilized to model the trajectories of maternal depressive symptoms, measured using the Edinburgh Postnatal Depression Scale (EPDS), and general anxiety, measured with Symptom Checklist-90 (SCL-90) at 14, 24, and 34 weeks' gestation (gw) and at 3, 6 and 24 months postpartum. Maternal depression was also assessed at 12 months. Child socio-emotional problems and competence were evaluated using the Brief Infant Toddler Social Emotional Assessment (BITSEA) at 2 years and Strengths and Difficulties Questionnaire (SDQ) at 5 years. Relevant background factors and maternal concurrent symptomatology were controlled for.The trajectories of maternal depressive and anxiety symptoms were associated negatively with differential aspects of child long term socio-emotional outcomes from early toddlerhood to preschool years. The trajectories of depressive symptoms and high-level persistent symptoms that continued from pregnancy to two years of child age had the strongest negative association with child outcomes. This highlights the importance of identifying and treating maternal symptomatology, especially that of depression, as early as possible.