Infectious diseases and immune system in infants Risk factors and consequences: The Generation R Study

Preterm birth and low birth weight are considered as important public health concerns since both are important causes of perinatal morbidity and mortality (1-3). Furthermore, these adverse birth outcomes seem to have long term consequences. Preterm birth infants are at risk for neurodevelopmental problems (4). Low birth weight infants are at risk for the development of coronary heart disease and diabetes mellitus (5). Several determinants of preterm birth and low birth weight have been identifi ed, including biological, genetic and socio-demographic determinants (6-8). Of the biological determinants, Chlamydia trachomatis during pregnancy may lead to low birth weight, preterm birth, premature rupture of membranes and other adverse pregnancy outcomes (9-11). However, the literature regarding the adverse eff ects of these infections yields confl icting results mainly due to diff erences in study design and population and microbiological tests employed (12-22). Laboratory testing on C. trachomatis or other urogenital infections during pregnancy is not routinely performed. Specifi c antenatal attention for urogenital symptoms, indicating a possible underlying urogenital tract infection, may be helpful in identifying women at increased risk for delivering preterm or low birth weight infants. Not much is known of the eff ects of urogenital symptoms in diff erent periods of pregnancy with pregnancy outcomes. This may be relevant for identifying critical periods during pregnancy that could be used for targeting preventive strategies

Invloed van DNA-methylatie op gezondheid en ziekte van kinderen

De ontwikkeling in de eerste fase van het leven is van groot belang voor de gezondheid van kinderen en volwassenen. Ongunstige invloeden in specifieke kritieke perioden tijdens de vroege ontwikkeling hebben nadelige effecten op de gezondheid op latere leeftijd. Er zijn steeds meer aanwijzingen dat vroege en permanente epigenetische veranderingen een belangrijke rol spelen in de onderliggende mechanismen. In dit artikel bespreken wij de rol van DNA-methylatie, het bekendste epigenetische mechanisme, op gezondheid en ziekte van kinderen. Wij gaan in op de achtergrond van DNA-methylatie, op factoren die hierop van invloed zijn en op gevolgen van DNA-methylatie. Onderzoek gericht op het identificeren van factoren tijdens en kort na de zwangerschap die via epigenetische mechanismen bijdragen aan de kans op ziekten, moet uiteindelijk leiden tot preventieprogramma’s gericht op de vroegste fase van het leven

Airway bacterial carriage and childhood respiratory health: A population-based prospective cohort study

Background Airway bacterial carriage might play a role in respiratory disease. We hypothesize that nasal carriage with Staphylococcus aureus or nasopharyngeal carriage with Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae predisposes individuals to adverse respiratory health. Objective To examine the association of early‐life airway bacterial carriage with respiratory tract infections and vice versa, and of early‐life airway bacterial carriage with wheezing, lung function, and asthma in later childhood. Methods We collected upper airway swabs for bacterial culturing for S aureus, H influenzae, M catarrhalis, and H influenzae at six timepoints between the ages of 6 weeks and 6 years among 945 children participating in a population‐based prospective cohort study. Information on respiratory tract infections and wheezing until age 6 years, and asthma at age 10 years was obtained by questionnaires. Lung function at age 10 years was measured by spirometry. We tested possible bidirectional associations between airway bacterial carriage and respiratory tract infections by cross‐lagged models, and associations of repeatedly measured airway bacterial carriage with wheezing, lung function, and asthma by generalized estimating equations models and regression models. Results Cross‐lagged modeling showed that early‐life airway bacterial carriage was not consistently associated with upper and lower respiratory tract infections or vice versa. Nasopharyngeal carriage with any bacteria in infancy was associated with an increased risk of wheezing (OR [95% CI]: 1.66 [1.31, 2.10]). Airway bacterial carriage was not consistently associated with school‐age lung function or asthma. Conclusion Nasopharyngeal carriage with any bacteria is associated with wheezing, but not respiratory tract infections, asthma, or lung function

Associations of eczema phenotypes with emotional and behavioural problems from birth until school age. The Generation R Study.

Background Eczema phenotypes and emotional and behavioural problems are highly prevalent in childhood, but their mutual relationship is not fully clear. Objectives To examine the associations of eczema phenotypes with school-age emotional and behavioural problems, and the bidirectional associations of eczema and emotional and behavioural problems from birth until 10 years. Methods This study among 5265 individuals was embedded in a prospective population-based cohort study. Never, early transient, mid-transient, late transient and persistent eczema phenotypes were identified based on parent-reported, physician-diagnosed eczema from age 6 months until 10 years. Emotional (internalizing) and behavioural (externalizing) problems were measured repeatedly using the Child Behavior Checklist from age 15 to 10 years. Cross-lagged models were applied for bidirectional analyses. Results All eczema phenotypes were associated with more internalizing problems and attention problems at age 10 years, compared with never having eczema: range of Z-score differences 014 [95% confidence interval (CI) 001–027] to 039 (95% CI 018–060). Children with early transient eczema had more aggressive behaviour symptoms at age 10 years (Z = 016, 95% CI 005–027). Bidirectional analysis showed that eczema at 0–2 years was associated with more internalizing and externalizing problems at ages 3–6 and 10 years, while, inversely, only internalizing problems at 0–2 years were associated with an increased risk of eczema at age 10 years. Conclusions Eczema phenotypes are very modestly associated with more somatic symptoms and attention problems at school age. Early transient eczema is associated with more aggressive behaviour symptoms. Directional effects seem to occur from early-life eczema to later-life internalizing and externalizing problems, rather than the reverse

Maternal hemoglobin and iron status in early pregnancy and childhood cardiac outcomes

Background & aims: Dysregulation of iron homeostasis is associated with cardiac alterations in a sex-dependent manner in adults. It is unknown whether iron status during pregnancy has long-term impact on cardiovascular health, and if this association is influenced by sex. Therefore, this study aimed to evaluate sex-specific association between maternal iron status during early pregnancy and cardiac outcomes in children aged 10 years. Methods: In a population-based cohort study among 1972 mother–child pairs, hemoglobin and ferritin were measured in early pregnancy (150 μg/L). At 10 years of age, cardiac MRI was performed to measure right and left cardiac outcomes of function (ventricular end-diastolic volume (RVEDV and LVEDV) and ejection fraction (RVEF and LVEF)), and structure (left ventricular mass (LVM), and left ventricular mass-to-volume ratio (LMVR)). Results are presented for boys and girls separately and models were adjusted for confounders and multiple testing. Results: In boys, one standard deviation score (SDS) increase in maternal hemoglobin was associated with lower RVEDV and LVEDV (difference (95%CI) −0.10 (−0.17, −0.03) SDS and −0.09 (−0.16, −0.03) SDS, respectively). In boys, maternal anemia, as compared to normal hemoglobin levels, was associated with higher LVEDV (difference 0.34 (0.10, 0.59) SDS). No associations were observed for other cardiac outcomes and for ferritin in boys. No associations were observed in girls. Conclusion: In boys, dysregulated iron status during early pregnancy might permanently alter cardiovascular RVEDV and LVEDV function. Underlying mechanisms need further study. © 2024 The AuthorsThe Generation R Study is made possible by financial support from the Erasmus Medical Centre, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. Hugo G. Quezada-Pinedo received funding from Academy Ter Meulen grant of the Academy Medical Sciences Fund of the Royal Netherlands Academy of Arts & Sciences (grant agreement No KNAWWF/1327/TMB202116). Susana Santos was supported by the European Union Horizon Europe Research and Innovation Programme under the Marie Sklodowska-Curie Postdoctoral Fellowship Grant Agreement No. 101109136 (URBANE). The researchers are independent from the funders. The study sponsors had no role in the study design, data analysis, interpretation of data, or writing of this report

Chest computed tomography in severe bronchopulmonary dysplasia:Comparing quantitative scoring methods

Purpose: Bronchopulmonary dysplasia (BPD) is the most common complication of extreme preterm birth and structural lung abnormalities are frequently found in children with BPD. To quantify lung damage in BPD, three new Hounsfield units (HU) based chest-CT scoring methods were evaluated in terms of 1) intra- and inter-observer variability, 2) correlation with the validated Perth-Rotterdam-Annotated-Grid-Morphometric-Analysis (PRAGMA)-BPD score, and 3) correlation with clinical data. Methods: Chest CT scans of children with severe BPD were performed at a median of 7 months corrected age. Hyper- and hypo-attenuated regions were quantified using PRAGMA-BPD and three new HU based scoring methods (automated, semi-automated, and manual). Intra- and inter-observer variability was measured using intraclass correlation coefficients (ICC) and Bland-Altman plots. The correlation between the 4 scoring methods and clinical data was assessed using Spearman rank correlation. Results: Thirty-five patients (median gestational age 26.1 weeks) were included. Intra- and inter-observer variability was excellent for hyper- and hypo-attenuation regions for the manual HU method and PRAGMA-BPD (ICCs range 0.80–0.97). ICC values for the semi-automated HU method were poorer, in particular for the inter-observer variability of hypo- (0.22–0.71) and hyper-attenuation (-0.06–0.89). The manual HU method was highly correlated with PRAGMA-BPD score for both hyper- (ρs0.92, p &lt; 0.001) and hypo-attenuation (ρs0.79, p &lt; 0.001), while automated and semi-automated HU methods showed poor correlation for hypo- (ρs &lt; 0.22) and good correlation for hyper-attenuation (ρs0.72–0.74, p &lt; 0.001). Several scores of hyperattenuation correlated with the use of inhaled bronchodilators in the first year of life; two hypoattenuation scores correlated with birth weight. Conclusions: PRAGMA-BPD and the manual HU method have the best reproducibility for quantification of CT abnormalities in BPD.</p

Liver Fat and Cardiometabolic Risk Factors Among School-Age Children

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease is a major risk factor for cardiometabolic disease in adults. The burden of liver fat and associated cardiometabolic risk factors in healthy children is unknown. In a

Population screening for gestational hypertensive disorders using maternal, fetal and placental characteristics

Objective: To determine screening performance of maternal, fetal and placental characteristics for selecting pregnancies at risk of gestational hypertension and preeclampsia in a low-risk multi-ethnic population. Method: In a prospective population-based cohort among 7124 pregnant women, we collected maternal characteristics including body mass index, ethnicity, parity, smoking and blood pressure in early-pregnancy. Fetal characteristics included second and third trimester estimated fetal weight and sex determined by ultrasound. Placental characteristics included first and second trimester placental growth factor concentrations and second and third trimester uterine artery resistance indices. Results: Maternal characteristics provided the best screening result for gestational hypertension (area-under-the-curve [AUC] 0.79 [95% Confidence interval {CI} 0.76-0.81]) with 40% sensitivity at 90% specificity. For preeclampsia, the maternal characteristics model led to a screening performance of AUC 0.74 (95% CI 0.70-0.78) with 33% sensitivity at 90% specificity. Addition of second and third trimester placental ultrasound characteristics only improved screening performance for preeclampsia (AUC 0.78 [95% CI 0.75-0.82], with 48% sensitivity at 90% specificity). Conclusion: Routinely measured maternal characteristics, known at the start of pregnancy, can be used in screening for pregnancies at risk of gestational hypertension or preeclampsia within a low-risk multi-ethnic population. Addition of combined second and third trimester placental ultrasound characteristics only improved screening for preeclampsia

Residential Proximity to Major Roadways at Birth, DNA Methylation at Birth and Midchildhood, and Childhood Cognitive Test Scores: Project Viva(Massachusetts, USA).

BackgroundEpigenetic variability is hypothesized as a regulatory pathway through which prenatal exposures may influence child development and health.ObjectiveWe sought to examine the associations of residential proximity to roadways at birth and epigenome-wide DNA methylation. We also assessed associations of differential methylation with child cognitive outcomes.MethodsWe estimated residential proximity to roadways at birth using a geographic information system (GIS) and cord blood methylation using Illumina's HumanMethylation450-array in 482 mother-child pairs in Project Viva. We identified individual CpGs associated with residential-proximity-to-roadways at birth using robust linear regression [[Formula: see text]]. We also estimated association between proximity-to-roadways at birth and methylation of the same sites in blood samples collected at age 7-11 y ([Formula: see text]). We ran the same analyses in the Generation R Study for replication ([Formula: see text]). In Project Viva, we investigated associations of differential methylation at birth with midchildhood cognition using linear regression.ResultsLiving closer to major roadways at birth was associated with higher cord blood (and-more weakly-midchildhood blood) methylation of four sites in LAMB2. For each halving of residential-proximity-to-major-roadways, we observed a 0.82% increase in DNA methylation at cg05654765 [95% confidence interval (CI): (0.54%, 1.10%)], 0.88% at cg14099457 [95% CI: (0.56%, 1.19%)], 0.19% at cg03732535 [95% CI: (0.11%, 0.28)], and 1.08% at cg02954987 [95% CI: (0.65%, 1.51%)]. Higher cord blood methylation of these sites was associated with lower midchildhood nonverbal cognitive scores. Our results did not replicate in the Generation R Study.ConclusionsOur discovery results must be interpreted with caution, given that they were not replicated in a separate cohort. However, living close to major roadways at birth was associated with cord blood methylation of sites in LAMB2-a gene known to be linked to axonal development-in our U.S. cohort. Higher methylation of these sites associated with lower nonverbal cognitive scores at age 7-11 y in the same children. https://doi.org/10.1289/EHP2034

Second and third trimester fetal ultrasound population screening for risks of preterm birth and small-size and large-size for gestational age at birth: a population-based prospective cohort study

BACKGROUND: Preterm birth, small size for gestational age (SGA) and large size for gestational age (LGA) at birth are major risk factors for neonatal and long-term morbidity and mortality. It is unclear which periods of pregnancy are optimal for ultrasound screening to identify fetuses at risk of preterm birth, SGA or LGA at birth. We aimed to examine whether single or combined second and third trimes