Biallelic PKP2 loss of function variants are associated with a lethal perinatal-onset biventricular dilated cardiomyopathy with excessive trabeculations and ventricular septal defects.

Homozygous plakophilin-2 (PKP2) variants have been identified as a cause of a lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET) in three cases. We report three more cases from two families with homozygous pathogenic PKP2 variants and perinatal-onset, lethal DCM-ET. Identification of the genetic abnormalities played a key role in decision-making and family counselling in these cases. This case series supports the published evidence that biallelic loss of function PKP2 variants cause a lethal, perinatal-onset cardiomyopathy.

Novel mutation leading to splice donor loss in a conserved site of DMD gene causes Duchenne muscular dystrophy with cryptorchidism.

BACKGROUND: As one of the most common congenital abnormalities in male births, cryptorchidism has been found to have a polygenic aetiology according to previous studies of common variants. However, little is known about genetic predisposition of rare variants for cryptorchidism, since rare variants have larger effective size on diseases than common variants. METHODS: In this study, a cohort of 115 Chinese probands with cryptorchidism was analysed using whole-genome sequencing, alongside 19 parental controls and 2136 unaffected men. Additionally, CRISPR-Cas9 editing of a conserved variant was performed in a mouse model, with MRI screening used to observe the phenotype. RESULTS: In 30 of 115 patients (26.1%), we identified four novel genes (ARSH, DMD, MAGEA4 and SHROOM2) affecting at least five unrelated patients and four known genes (USP9Y, UBA1, BCORL1 and KDM6A) with the candidate rare pathogenic variants affecting at least two cases. Burden tests of rare variants revealed the genome-wide significances for newly identified genes (p<2.5×10-6) under the Bonferroni correction. Surprisingly, novel and known genes were mainly found on X chromosome (seven on X and one on Y) and all rare X-chromosomal segregating variants exhibited a maternal inheritance rather than de novo origin. CRISPR-Cas9 mouse modelling of a splice donor loss variant in DMD (NC_000023.11:g.32454661C>G), which resides in a conserved site across vertebrates, replicated bilateral cryptorchidism phenotypes, confirmed by MRI at 4 and 10 weeks. The movement tests further revealed symptoms of Duchenne muscular dystrophy (DMD) in transgenic mice. CONCLUSION: Our results revealed the role of the DMD gene mutation in causing cryptorchidism. The results also suggest that maternal-X inheritance of pathogenic defects could have a predominant role in the development of cryptorchidism.

No association between long-chain n-3 fatty acid intake during pregnancy and risk of type 1 diabetes in offspring in two large Scandinavian pregnancy cohorts.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether higher dietary intake of marine n-3 fatty acids during pregnancy is associated with a lower risk of type 1 diabetes in children. METHODS: The Danish National Birth Cohort (DNBC) and the Norwegian Mother, Father and Child Cohort Study (MoBa) together include 153,843 mother-child pairs with prospectively collected data on eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake during pregnancy from validated food frequency questionnaires. Type 1 diabetes diagnosis in children (n=634) was ascertained from national diabetes registries. RESULTS: There was no association between the sum of EPA and DHA intake during pregnancy and risk of type 1 diabetes in offspring (pooled HR per g/day of intake: 1.00, 95% CI 0.88, 1.14), with consistent results for both the MoBa and the DNBC. Robustness analyses gave very similar results. CONCLUSIONS/INTERPRETATION: Initiation of a trial of EPA and DHA during pregnancy to prevent type 1 diabetes in offspring should not be prioritised.

Next Generation, Modifiable Cardiometabolic Biomarkers: Mitochondrial Adaptation and Metabolic Resilience: A Scientific Statement From the American Heart Association.

Cardiometabolic risk is increasing in prevalence across the life span with disproportionate ramifications for youth at socioeconomic disadvantage. Established risk factors and associated disease progression are harder to reverse as they become entrenched over time; if current trends are unchecked, the consequences for individual and societal wellness will become untenable. Interrelated root causes of ectopic adiposity and insulin resistance are understood but identified late in the trajectory of systemic metabolic dysregulation when traditional cardiometabolic risk factors cross current diagnostic thresholds of disease. Thus, children at cardiometabolic risk are often exposed to suboptimal metabolism over years before they present with clinical symptoms, at which point life-long reliance on pharmacotherapy may only mitigate but not reverse the risk. Leading-edge indicators are needed to detect the earliest departure from healthy metabolism, so that targeted, primordial, and primary prevention of cardiometabolic risk is possible. Better understanding of biomarkers that reflect the earliest transitions to dysmetabolism, beginning in utero, ideally biomarkers that are also mechanistic/causal and modifiable, is critically needed. This scientific statement explores emerging biomarkers of cardiometabolic risk across rapidly evolving and interrelated "omic" fields of research (the epigenome, microbiome, metabolome, lipidome, and inflammasome). Connections in each domain to mitochondrial function are identified that may mediate the favorable responses of each of the omic biomarkers featured to a heart-healthy lifestyle, notably to nutritional interventions. Fuller implementation of evidence-based nutrition must address environmental and socioeconomic disparities that can either facilitate or impede response to therapy.

How the Environmental influences on Child Health Outcome (ECHO) Cohort can spur discoveries in environmental epidemiology.

NIH's Environmental influences on Child Health Outcome (ECHO) program is an innovative, large, collaborative research initiative whose mission is to enhance the health of children for generations to come. The goal of the ECHO Cohort is to examine effects of a broad array of early environmental exposures on child health and development. It includes longitudinal data and biospecimens from over 100,000 children and family members from diverse settings across the U.S. ECHO investigators have published collaborative analyses showing associations of environmental exposures--primarily in the developmentally sensitive pre-, peri-, and post-natal periods--with preterm birth and childhood asthma, obesity, neurodevelopment, and positive health. Investigators have addressed health disparities, joint effects of environmental and social determinants, and effects of mixtures of chemicals. The ECHO Cohort is now entering its second 7-year cycle (2023-2030), which will add the preconception period to its current focus on prenatal through adolescence. Through a controlled access public use database, ECHO makes its deidentified data available to the general scientific community. ECHO Cohort data provide opportunities to fill major knowledge gaps in in environmental epidemiology, and to inform policies, practices, and programs to enhance child health.

The Study of the Epidemiology of Pediatric Hypertension Registry (SUPERHERO): Rationale and Methods.

Despite increasing prevalence of hypertension in youth and high adult cardiovascular mortality rates, the long-term consequences of youth-onset hypertension remain unknown. This is due to limitations of prior research such as small sample sizes, reliance on manual record review, and limited analytic methods that did not address major biases. The Study of the Epidemiology of Pediatric Hypertension (SUPERHERO) is a multisite retrospective Registry of youth evaluated by subspecialists for hypertension disorders. Sites obtain harmonized electronic health record data using standardized biomedical informatics scripts validated with randomized manual record review. Inclusion criteria are index visit for International Classification of Diseases Diagnostic Codes, 10th Revision (ICD-10 code)-defined hypertension disorder ≥January 1, 2015 and age <19 years. We exclude patients with ICD-10 code-defined pregnancy, kidney failure on dialysis, or kidney transplantation. Data include demographics, anthropomorphics, U.S. Census Bureau tract, histories, blood pressure, ICD-10 codes, medications, laboratory and imaging results, and ambulatory blood pressure. SUPERHERO leverages expertise in epidemiology, statistics, clinical care, and biomedical informatics to create the largest and most diverse registry of youth with newly diagnosed hypertension disorders. SUPERHERO's goals are to (i) reduce CVD burden across the life course and (ii) establish gold-standard biomedical informatics methods for youth with hypertension disorders.

Evolution in key indicators of maternal and child health across the wealth gradient in 41 sub-Saharan African countries, 1986-2019.

BACKGROUND: Aggregate trends can be useful for summarizing large amounts of information, but this can obscure important distributional aspects. Some population subgroups can be worse off even as averages climb, for example. Distributional information can identify health inequalities, which is essential to understanding their drivers and possible remedies. METHODS: Using publicly available Demographic and Health Survey (DHS) data from 41 sub-Saharan African countries from 1986 to 2019, we analyzed changes in coverage for eight key maternal and child health indicators: first dose of measles vaccine (MCV1); Diphtheria-Pertussis-Tetanus (DPT) first dose (DPT1); DPT third dose (DPT3); care-seeking for diarrhea, acute respiratory infections (ARI), or fever; skilled birth attendance (SBA); and having four antenatal care (ANC) visits. To evaluate whether coverage diverged or converged over time across the wealth gradient, we computed several dispersion metrics including the coefficient of variation across wealth quintiles. Slopes and 5-year moving averages were computed to identify overall long-term trends. RESULTS: Average coverage increased for all quintiles and indicators, although the range and the speed at which they increased varied widely. There were small changes in the wealth-related gap for SBA, ANC, and fever. The wealth-related gap of vaccination-related indicators (DPT1, DPT3, MCV1) decreased over time. Compared to 2017, the wealth-gap between richest and poorest quintiles in 1995 was 7 percentage points larger for ANC and 17 percentage points larger for measles vaccination. CONCLUSIONS: Maternal and child health indicators show progress, but the distributional effects show differential evolutions in inequalities. Several reasons may explain why countries had smaller wealth-related gap trends in vaccination-related indicators compared to others. In addition to service delivery differences, we hypothesize that the allocation of development assistance for health, the prioritization of vaccine-preventable diseases on the global agenda, and indirect effects of structural adjustment programs on health system-related indicators might have played a role.

Impact of mHealth interventions on maternal, newborn, and child health from conception to 24 months postpartum in low- and middle-income countries: a systematic review.

BACKGROUND: Mobile health (mHealth) technologies have been harnessed in low- and middle-income countries (LMICs) to address the intricate challenges confronting maternal, newborn, and child health (MNCH). This review aspires to scrutinize the effectiveness of mHealth interventions on MNCH outcomes during the pivotal first 1000 days of life, encompassing the period from conception through pregnancy, childbirth, and post-delivery, up to the age of 2 years. METHODS: A comprehensive search was systematically conducted in May 2022 across databases, including PubMed, Cochrane Library, Embase, Cumulative Index to Nursing & Allied Health (CINAHL), Web of Science, Scopus, PsycINFO, and Trip Pro, to unearth peer-reviewed articles published between 2000 and 2022. The inclusion criteria consisted of (i) mHealth interventions directed at MNCH; (ii) study designs, including randomized controlled trials (RCTs), RCT variations, quasi-experimental designs, controlled before-and-after studies, or interrupted time series studies); (iii) reports of outcomes pertinent to the first 1000 days concept; and (iv) inclusion of participants from LMICs. Each study was screened for quality in alignment with the Cochrane Handbook for Systematic Reviews of Interventions and the Joanne Briggs Institute Critical Appraisal tools. The included articles were then analyzed and categorized into 12 mHealth functions and outcome domain categories (antenatal, delivery, and postnatal care), followed by forest plot comparisons of effect measures. RESULTS: From the initial pool of 7119 articles, we included 131 in this review, comprising 56 RCTs, 38 cluster-RCTs, and 37 quasi-experimental studies. Notably, 62% of these articles exhibited a moderate or high risk of bias. Promisingly, mHealth strategies, such as dispatching text message reminders to women and equipping healthcare providers with digital planning and scheduling tools, exhibited the capacity to augment antenatal clinic attendance and enhance the punctuality of child immunization. However, findings regarding facility-based delivery, child immunization attendance, and infant feeding practices were inconclusive. CONCLUSIONS: This review suggests that mHealth interventions can improve antenatal care attendance and child immunization timeliness in LMICs. However, their impact on facility-based delivery and infant feeding practices varies. Nevertheless, the potential of mHealth to enhance MNCH services in resource-limited settings is promising. More context-specific implementation studies with rigorous evaluations are essential.

Risk of Incident Asthma Among Young Asian American, Native Hawaiian, and Pacific Islander Children from Age 3 to 7 Years in a Northern California Healthcare System.

Incident childhood asthma risk has not been examined among diverse Asian American, Native Hawaiian, and Pacific Islander subgroups. In a large California healthcare system, incident asthma was higher among young Filipino/a, Native Hawaiian/Pacific Islander, and South Asian children compared with non-Hispanic White children, whereas Chinese and Japanese children were similar.

A Decade of Efforts to Add Value to Child Health Research Practices.

OBJECTIVE: To identify practices that add value to improve the design, conduct, and reporting of child health research and reduce research waste. STUDY DESIGN: In order to categorize the contributions of members of Standards for Research (StaR) in Child Health network, we developed a novel Child Health Improving Research Practices (CHIRP) framework comprised of 5 domains meant to counteract avoidable child health research waste and improve quality: 1) address research questions relevant to children, their families, clinicians, and researchers; 2) apply appropriate research design, conduct and analysis; 3) ensure efficient research oversight and regulation; 4) Provide accessible research protocols and reports; and 5) develop unbiased and usable research reports, including 17 responsible research practice recommendations. All child health research relevant publications by the 48 original StaR standards' authors over the last decade were identified, and main topic areas were categorized using this framework. RESULTS: A total of 247 publications were included in the final sample: 100 publications (41%) in domain 1 (3 recommendations), 77 publications (31%) in domain 2 (3), 35 publications (14%) in domain 3 (4), 20 publications (8%) in domain 4 (4), and 15 publications (6%) in domain 5 (3). We identified readily implementable "responsible" research practices to counter child health research waste and improve quality, especially in the areas of patients and families' engagement throughout the research process, developing Core Outcome Sets, and addressing ethics and regulatory oversight issues. CONCLUSION: While most of the practices are readily implementable, increased awareness of methodological issues and wider guideline uptake is needed to improve child health research. The CHIRP Framework can be used to guide responsible research practices that add value to child health research.

Quantifying the Association between Pump Use and Breastfeeding Duration.

OBJECTIVE: To quantify the extent to which pump use is associated with breastfeeding duration. STUDY DESIGN: We conducted a cross-sectional analysis of weighted data from the Centers for Disease Control and Prevention Pregnancy Risk Assessment Monitoring System from Maine, Michigan, New Mexico, and Utah between 2016 and 2021. Included respondents had a live-born infant at survey completion, initiated breastfeeding, and had nonmissing data for reported pump use and breastfeeding duration. Using Cox proportional hazard regression, we quantified the hazard of breastfeeding cessation and median duration (weeks) of breastfeeding by pump use. Pump use was suspected to be differentially impacted by race and ethnicity; an interaction was tested in our regression model. RESULTS: Our sample included 19 719 mothers (weighted n = 723 808) with mean age (SD) 29.5 years (5.6). Mothers with age <18 years, Medicaid enrollment, race, and ethnicity other than non-Hispanic White, lower income or education, and unmarried status demonstrated lower pump use (P < .001). Pump use was associated with 37% lower hazard of breastfeeding cessation (adjusted hazard ratio 0.63; 95% CI: 0.56-0.70) and 21 additional weeks of breastfeeding on average. The association varied by race and ethnicity (significant interaction observed between pump use and non-Hispanic Black mothers, P = .013); stratified analysis demonstrated the lowest hazard of breastfeeding cessation among non-Hispanic Black and Native American pump users (adjusted hazard ratio 0.47 [0.40-0.54] and 0.51 [0.37-0.70], respectively). CONCLUSIONS: Pump use was associated with longer breastfeeding duration; the greatest magnitudes of association were found among non-Hispanic Black and Native American participants, groups disproportionately affected by breastfeeding inequities. Future research examining the context around and causal impact of pump use on breastfeeding outcomes is needed.

Cohort-Based Reference Values for Serum Ferritin and Transferrin and Longitudinal Determinants of Iron Status in European Children Aged 3-15 Years.

BACKGROUND: Reference values of ferritin and transferrin for European children do not exist. OBJECTIVE: We aimed to provide sex-, age-, and body mass index (BMI)-specific serum ferritin and transferrin reference percentiles of 3-15-y-old children based on cohort data and to investigate determinants of iron status. METHODS: A total of 3390 ferritin and 3416 transferrin measurements from children residing in 8 European countries participating in the IDEFICS/I.Family cohort (https://www.isrctn.com/ISRCTN62310987) at baseline (W0) and 6 y later (W3) were used to estimate percentiles using the generalized additive model for location, scale and shape. Associations of serum ferritin and transferrin concentrations with total iron intake, total iron intake additionally adjusted for vitamin C intake, and iron from heme sources were investigated separately with adjustment for sex, age, country of residence, parental education, usual energy intake and BMI z-score in regression models using cross-sectional and longitudinal data. RESULTS: The age-specific ferritin and transferrin 5th and 95th reference percentiles ranged from 10.9 to 81.1 µg/L and 2.23 to 3.56 g/L, respectively. A deficient iron status was observed in 3% of children at W0 and 7% of children and adolescents at W3, respectively. At both waves, a higher iron intake from heme sources was positively associated with serum ferritin {W0: ß = 3.21 [95% confidence interval (CI): 0.71, 5.71]; W3: ß = 4.48 [95% CI: 2.09, 6.87]}, that is, children consuming one mg more heme iron had a 3.21 and 4.48 µg/L higher ferritin concentration. Adherence to a mainly vegetarian diet was associated with a lower chance for sufficient serum ferritin cross-sectionally at W3 [odds ratio (OR) 0.40 (95% CI: 0.21, 0.81)] and longitudinally [OR 0.35 (95% CI: 0.15, 0.93)]. CONCLUSIONS: Age-, sex-, and BMI-specific reference percentiles of serum ferritin and transferrin concentrations based on cohort data are provided for European children aged 3-15 y and may be used in clinical practice.

Prescription for Cash? Cash Support to Low-Income Families in Maternal and Pediatric Health Care Settings.

Policy Points Pregnancy and childhood are periods of heightened economic vulnerability, but current policies for addressing health-related social needs, including screening and referral programs, may be insufficient because of persistent gaps, incomplete follow-up, administrative burden, and limited take-up. To bridge gaps in the social safety net, direct provision of cash transfers to low-income families experiencing health challenges during pregnancy, infancy, and early childhood could provide families with the flexibility and support to enable caregiving, increase access to health care, and improve health outcomes.

Impact of seasonal malaria chemoprevention based on the number of medicines doses received on malaria burden among children aged 3-59 months in Nigeria: A propensity score-matched analysis.

BACKGROUND: Seasonal malaria chemoprevention using sulfadoxine-pyrimethamine plus amodiaquine (sulfadoxine-pyrimethamine plus amodiaquine on Day 1 and amodiaquine on both Day 2 and Day 3) is delivered to children aged 3-59 months in areas of highly season malaria transmission. While the overall population-level impact of seasonal malaria chemoprevention on malaria control has been documented in various countries and time periods, there is no clear evidence regarding seasonal malaria chemoprevention impact based on the number of medicine doses children receive in one cycle in routine programmatic conditions. METHODS: Data were extracted from Nigeria's routinely collected seasonal malaria chemoprevention end-of-round coverage surveys (2021, 2022). We matched seasonal malaria chemoprevention-targeted children who received specific numbers of seasonal malaria chemoprevention medicines with those who did not receive any doses of seasonal malaria chemoprevention medicines (non-sulfadoxine-pyrimethamine plus amodiaquine) using multiple sets of propensity score matches. We performed multilevel logistic regression for each matched group to evaluate the association between the number of doses of seasonal malaria chemoprevention medicines and monthly confirmed malaria cases (caregiver-reported malaria infection diagnosed by rapid diagnostic test at a health facility following the penultimate cycle of seasonal malaria chemoprevention). RESULTS: Among 21,621 SMC-targeted children, 9.7% received non-sulfadoxine-pyrimethamine plus amodiaquine, 0.5% received only Day 1 sulfadoxine-pyrimethamine plus amodiaquine, 1.0% received Day 1 sulfadoxine-pyrimethamine plus amodiaquine and either Day 2 amodiaquine or Day 3 amodiaquine (sulfadoxine-pyrimethamine plus amodiaquine + amodiaquine), and 88.8% received Day 1 sulfadoxine-pyrimethamine plus amodiaquine and both Day 2 and Day 3 amodiaquine (sulfadoxine-pyrimethamine plus amodiaquine + amodiaquine + amodiaquine). Children receiving only Day 1 sulfadoxine-pyrimethamine plus amodiaquine did not have significant lower odds of rapid diagnostic tests-confirmed malaria than those receiving non-sulfadoxine-pyrimethamine plus amodiaquine (OR 0.77, 0.42-1.42). However, children receiving sulfadoxine-pyrimethamine plus amodiaquine + amodiaquine had significantly lower odds of rapid diagnostic tests-confirmed malaria than those receiving non-sulfadoxine-pyrimethamine plus amodiaquine (OR 0.42, 95% CI 0.28-0.63). Similarly, children receiving sulfadoxine-pyrimethamine plus amodiaquine + amodiaquine + amodiaquine also had significantly lower odds of rapid diagnostic test-confirmed malaria than those receiving non-sulfadoxine-pyrimethamine plus amodiaquine (OR 0.54, 95% CI 0.47-0.62). CONCLUSION: Adherence to at least one daily dose of amodiaquine administration following receipt of Day 1 sulfadoxine-pyrimethamine plus amodiaquine by eligible children is crucial to ensure the effectiveness of seasonal malaria chemoprevention. This demonstrates the importance of enhancing caregiver awareness regarding the importance of amodiaquine and identifying barriers toward amodiaquine administration at the community level.

Determinants of diarrheal disease in children undergoing complementary feeding in a low-income urban setting in Kenya.

OBJECTIVES: This study aimed to identify and characterise the determinants influencing the occurrence of diarrheal diseases in children aged 6-24 months undergoing complementary feeding within a low-income urban community in Kenya. METHODS: This study followed a cross-sectional design and recruited caregivers of children aged 6-24 months from 302 households. The dependent variable was the 2-week diarrhoea prevalence among children, with independent variables including sociodemographic characteristics, child immunisation and feeding status, and water and sanitation facilities. Data analysis was performed using SPSS. Descriptive statistics and logistic regression analyses were used to assess associations between independent variables and the occurrence of diarrheal diseases. RESULTS: The majority of caregivers were female (n = 282, 93.4%), aged 25-34 years (n = 156, 51.7%), had attained secondary school education (n = 154, 51%), were unemployed (n = 162, 53.6%), and earned Ksh 10,000 (USD 100) or less. 296 (98%) indexed children were fully vaccinated against rotavirus. Most households used improved drinking water sources (n = 272, 90.1%). Most caregivers did not regularly wash their hands with soap and water (n = 225, 74.5%). The 2-week diarrhoea prevalence among children was 34.1% (103/302), with 69.9% (72/103) of these cases seeking care at a healthcare facility. Logistic regression analysis revealed that children of caregivers earning Ksh 20,000 and below (aOR = 2.9[1.3-6.5], p = 0.01), and those from households using unimproved sanitation facilities (aOR = 1.9 [CI 1-3.4], p = 0.042), had significantly higher odds of having diarrhoea. CONCLUSION: The study found a high prevalence of diarrhoea in Kenyan children aged 6-24 months, with caregiver income and household sanitation facilities significantly impacting the occurrence of the disease. The study suggests integrated approaches, including education, income generation, hygiene, and improved nutrition, to address the burden of diarrheal disease.

Understanding pre-hospital disease management of fever and diarrhoea in children-Care pathways in rural Tanzania.

OBJECTIVE: Many children in sub-Saharan Africa die from infectious diseases like malaria, pneumonia, and diarrhoea that can be prevented by early diagnosis, effective and targeted treatment. This study aimed to gain insights into case management practices by parents before they present their children to hospital. METHODS: We conducted a cross-sectional study among 332 parents attending a district hospital with their under-fives symptomatic with fever and/or diarrhoea between November 2019 and July 2020 in rural Tanzania. Timely and targeted treatment was defined as seeking health care within 24 h of fever onset, and continued fluid intake in case of diarrhoea. RESULTS: The main admission diagnoses were acute respiratory infections (61.8%), malaria (25.3%), diarrhoea (18.4%) and suspected sepsis (8.1%). The majority of children (91%) received treatment prior to admission, mostly antipyretics (75.6%), local herbal medicines (26.8%), and antibiotics (17.8%)-half of them without prescription from a clinician. For diarrhoea, the use of oral rehydration solution was rare (9.0%), although perceived as easily accessible and affordable. 49.4% of the parents presented their children directly to the hospital, 23.2% went to a pharmacy/drug shop and 19.3% to a primary health facility first. Malaria symptoms began mostly 3 days before the hospital visit; only 25.4% of febrile children visited any health facility within 24 h of disease onset. Prior use of local herbal medicine (AOR = 3.2; 95% CI 1.4-7.3), visiting the pharmacy (adjusted Odds Ratio [AOR] = 3.1; 95% confidence interval [CI]: 1.0-9.8), the dispensary being the nearest health facility (AOR = 3.0; 95% CI: 1.5-6.2), and financial difficulties (AOR = 2.2; 95% CI 1.1-4.5) were associated with delayed treatment. CONCLUSION: This study suggests that antipyretics and antibiotics dispensed at pharmacies/drug shops, as well as use of local herbal medicines, delay early diagnosis and treatment, which can be life-threatening. Pharmacies/drug shops could be integrated as key focal points for sensitising community members on how to respond to paediatric illnesses and encourage the use of oral rehydration solutions.

Impact of hypertensive disorders of pregnancy and gestational diabetes mellitus on offspring cardiovascular health in early adolescence.

BACKGROUND: Adverse pregnancy outcomes, including hypertensive disorders of pregnancy and gestational diabetes mellitus, influence maternal cardiovascular health long after pregnancy, but their relationship to offspring cardiovascular health following in-utero exposure remains uncertain. OBJECTIVE: To examine associations of hypertensive disorders of pregnancy or gestational diabetes mellitus with offspring cardiovascular health in early adolescence. STUDY DESIGN: This analysis used data from the prospective Hyperglycemia and Adverse Pregnancy Outcome Study from 2000 to 2006 and the Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study from 2013 to 2016. This analysis included 3317 mother-child dyads from 10 field centers, comprising 70.8% of Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study participants. Those with pregestational diabetes and chronic hypertension were excluded. The exposures included having any hypertensive disorders of pregnancy or gestational diabetes mellitus vs not having hypertensive disorders of pregnancy or gestational diabetes mellitus, respectively (reference). The outcome was offspring cardiovascular health when aged 10-14 years, on the basis of 4 metrics: body mass index, blood pressure, total cholesterol level, and glucose level. Each metric was categorized as ideal, intermediate, or poor using a framework provided by the American Heart Association. The primary outcome was defined as having at least 1 cardiovascular health metric that was nonideal vs all ideal (reference), and the second outcome was the number of nonideal cardiovascular health metrics (ie, at least 1 intermediate metric, 1 poor metric, or at least 2 poor metrics vs all ideal [reference]). Modified poisson regression with robust error variance was used and adjusted for covariates at pregnancy enrollment, including field center, parity, age, gestational age, alcohol or tobacco use, child's assigned sex at birth, and child's age at follow-up. RESULTS: Among 3317 maternal-child dyads, the median (interquartile) ages were 30.4 (25.6-33.9) years for pregnant individuals and 11.6 (10.9-12.3) years for children. During pregnancy, 10.4% of individuals developed hypertensive disorders of pregnancy, and 14.6% developed gestational diabetes mellitus. At follow-up, 55.5% of offspring had at least 1 nonideal cardiovascular health metric. In adjusted models, having hypertensive disorders of pregnancy (adjusted risk ratio, 1.14 [95% confidence interval, 1.04-1.25]) or having gestational diabetes mellitus (adjusted risk ratio, 1.10 [95% confidence interval, 1.02-1.19]) was associated with a greater risk that offspring developed less-than-ideal cardiovascular health when aged 10-14 years. The above associations strengthened in magnitude as the severity of adverse cardiovascular health metrics increased (ie, with the outcome measured as ≥1 intermediate, 1 poor, and ≥2 poor adverse metrics), albeit the only statistically significant association was with the "1-poor-metric" exposure. CONCLUSION: In this multinational prospective cohort, pregnant individuals who experienced either hypertensive disorders of pregnancy or gestational diabetes mellitus were at significantly increased risk of having offspring with worse cardiovascular health in early adolescence. Reducing adverse pregnancy outcomes and increasing surveillance with targeted interventions after an adverse pregnancy outcome should be studied as potential avenues to enhance long-term cardiovascular health in the offspring exposed in utero.

Comparing population-based fetal growth standards in a US cohort.

BACKGROUND: No fetal growth standard is currently endorsed for universal use in the United States. Newer standards improve upon the methodologic limitations of older studies; however, before adopting into practice, it is important to know how recent standards perform at identifying fetal undergrowth or overgrowth and at predicting subsequent neonatal morbidity or mortality in US populations. OBJECTIVE: To compare classification of estimated fetal weight that is <5th or 10th percentile or >90th percentile by 6 population-based fetal growth standards and the ability of these standards to predict a composite of neonatal morbidity and mortality. STUDY DESIGN: We used data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be cohort, which recruited nulliparous women in the first trimester at 8 US clinical centers (2010-2014). Estimated fetal weight was obtained from ultrasounds at 16 to 21 and 22 to 29 weeks of gestation (N=9534 women). We calculated rates of fetal growth restriction (estimated fetal weight <5th and 10th percentiles; fetal growth restriction<5 and fetal growth restriction<10) and estimated fetal weight >90th percentile (estimated fetal weight>90) from 3 large prospective fetal growth cohorts with similar rigorous methodologies: INTERGROWTH-21, World Health Organization-sex-specific and combined, Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific and unified, and the historic Hadlock reference. To determine whether differential classification of fetal growth restriction or estimated fetal weight >90 among standards was clinically meaningful, we then compared area under the curve and sensitivity of each standard to predict small for gestational age or large for gestational age at birth, composite perinatal morbidity and mortality alone, and small for gestational age or large for gestational age with composite perinatal morbidity and mortality. RESULTS: The standards classified different proportions of fetal growth restriction and estimated fetal weight>90 for ultrasounds at 16 to 21 (visit 2) and 22 to 29 (visit 3) weeks of gestation. At visit 2, the Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific, World Health Organization sex-specific and World Health Organization-combined identified similar rates of fetal growth restriction<10 (8.4%-8.5%) with the other 2 having lower rates, whereas Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific identified the highest rate of fetal growth restriction<5 (5.0%) compared with the other references. At visit 3, World Health Organization sex-specific classified 9.2% of fetuses as fetal growth restriction<10, whereas the other 5 classified a lower proportion as follows: World Health Organization-combined (8.4%), Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific (7.7%), INTERGROWTH (6.2%), Hadlock (6.1%), and Eunice Kennedy Shriver National Institute of Child Health and Human Development unified (5.1%). INTERGROWTH classified the highest (21.3%) as estimated fetal weight>90 whereas Hadlock classified the lowest (8.3%). When predicting composite perinatal morbidity and mortality in the setting of early-onset fetal growth restriction, World Health Organization had the highest area under the curve of 0.53 (95% confidence interval, 0.51-0.53) for fetal growth restriction<10 at 22 to 29 weeks of gestation, but the areas under the curve were similar among standards (0.52). Sensitivity was generally low across standards (22.7%-29.1%). When predicting small for gestational age birthweight with composite neonatal morbidity or mortality, for fetal growth restriction<10 at 22 to 29 weeks of gestation, World Health Organization sex-specific had the highest area under the curve (0.64; 95% confidence interval, 0.60-0.67) and INTERGROWTH had the lowest (area under the curve=0.58; 95% confidence interval 0.55-0.62), though all standards had low sensitivity (7.0%-9.6%). CONCLUSION: Despite classifying different proportions of fetuses as fetal growth restriction or estimated fetal weight>90, all standards performed similarly in predicting perinatal morbidity and mortality. Classification of different percentages of fetuses as fetal growth restriction or estimated fetal weight>90 among references may have clinical implications in the management of pregnancies, such as increased antenatal monitoring for fetal growth restriction or cesarean delivery for suspected large for gestational age. Our findings highlight the importance of knowing how standards perform in local populations, but more research is needed to determine if any standard performs better at identifying the risk of morbidity or mortality.

Exposure to prenatal infection and the development of internalizing and externalizing problems in children: a longitudinal population-based study.

BACKGROUND: A large body of work has reported a link between prenatal exposure to infection and increased psychiatric risk in offspring. However, studies to date have focused primarily on exposure to severe prenatal infections and/or individual psychiatric diagnoses in clinical samples, typically measured at single time points, and without accounting for important genetic and environmental confounders. In this study, we investigated whether exposure to common infections during pregnancy is prospectively associated with repeatedly assessed child psychiatric symptoms in a large population-based study. METHODS: Our study was embedded in a prospective pregnancy cohort (Generation R; n = 3,598 mother-child dyads). We constructed a comprehensive prenatal infection score comprising common infections for each trimester of pregnancy. Child total, internalizing, and externalizing problems were assessed repeatedly using the parent-rated Child Behavioral Checklist (average age: 1.5, 3, 6, 10, and 14 years). Linear mixed-effects models were run adjusting for a range of confounders, including child polygenic scores for psychopathology, maternal chronic illness, birth complications, and infections during childhood. We also investigated trimester-specific effects and child sex as a potential moderator. RESULTS: Prenatal exposure to infections was associated with higher child total, internalizing, and externalizing problems, showing temporally persistent effects, even after adjusting for important genetic and environmental confounders. We found no evidence that prenatal infections were associated with changes in child psychiatric symptoms over time. Moreover, in our trimester-specific analysis, we did not find evidence of significant timing effects of prenatal infection on child psychiatric symptoms. No interactions with child sex were identified. CONCLUSIONS: Our research adds to evidence that common prenatal infections may be a risk factor for psychiatric symptoms in children. We also extend previous findings by showing that these associations are present early on, and that rather than changing over time, they persist into adolescence. However, unmeasured confounding may still explain in part these associations. In the future, employing more advanced causal inference designs will be crucial to establishing the degree to which these effects are causal.

The Longitudinal Reciprocal Relationships of Tooth Brushing Behaviors Between Underserved Children and Their Caregivers.

BACKGROUND: Tooth brushing is effective in preventing early childhood caries. However, it is unclear how children's and caregiver's tooth brushing are reciprocally related. PURPOSE: The current study investigated whether the longitudinal relationships between children and caregiver tooth brushing are moderated by a caregiver-targeted child oral health intervention and caregiver depression. METHODS: Secondary analysis of a randomized clinical trial that tested whether caregiver-targeted oral health text messages (OHT) outperformed child wellness text messages (CWT) on pediatric dental caries and oral health behaviors (n = 754, mean child age = 2.9 years, 56.2% Black, 68.3%

Tooth brushing is effective in preventing dental cavities in children, but we do not know if or how children and caregiver brushing frequencies are related. This is important because interventions targeting children's oral health may also have the potential to benefit their caregiver's behaviors. Our study examined whether caregiver brushing of their own teeth and caregiver brushing of their young child's teeth positively influenced each other over time. We also explored whether this relationship was less likely if caregivers experienced depressive symptoms and more likely if caregivers participated in a text message program focused on improving their child's oral health. Results showed that caregiver and child tooth brushing behaviors positively influenced each other over time, but this relationship was observed only in caregivers who received the child oral health program (as opposed to the control group) and who reported low depressive symptoms (in contrast to caregivers with high depression symptoms). Our findings suggest that while caregivers and children positively influence each other's tooth-brushing behaviors over time, additional support is essential for caregivers experiencing depression to fully realize these reciprocal benefits.