Gastro-Esophageal Reflux in Children

Gastro-esophageal reflux (GER) is common in infants and children and has a varied clinical presentation: from infants with innocent regurgitation to infants and children with severe esophageal and extra-esophageal complications that define pathological gastro-esophageal reflux disease (GERD). Although the pathophysiology is similar to that of adults, symptoms of GERD in infants and children are often distinct from classic ones such as heartburn. The passage of gastric contents into the esophagus is a normal phenomenon occurring many times a day both in adults and children, but, in infants, several factors contribute to exacerbate this phenomenon, including a liquid milk-based diet, recumbent position and both structural and functional immaturity of the gastro-esophageal junction. This article focuses on the presentation, diagnosis and treatment of GERD that occurs in infants and children, based on available and current guidelines

Disentangling nature from nurture in examining the interplay between parent–child relationships, ADHD, and early academic attainment

Background: Attention Deficit Hyperactivity Disorder (ADHD) is highly heritable and is associated with lower educational attainment. ADHD is linked to family adversity, including hostile parenting. Questions remain regarding the role of genetic and environmental factors underlying processes through which ADHD symptoms develop and influence academic attainment. Method: This study employed a parent-offspring adoption design (N=345) to examine the interplay between genetic susceptibility to child attention problems (birth mother ADHD symptoms) and adoptive parent (mother and father) hostility on child lower academic outcomes, via child ADHD symptoms. Questionnaires assessed birth mother ADHD symptoms, adoptive parent (mother and father) hostility to child, early child impulsivity/activation, and child ADHD symptoms. The Woodcock-Johnson test was used to examine child reading and math aptitude. Results: Building on a previous study (Harold et al., 2013), heritable influences were found: birth mother ADHD symptoms predicted child impulsivity/activation. In turn, child impulsivity/activation (4.5 years) evoked maternal and paternal hostility, which was associated with children’s ADHD continuity (6 years). Both maternal and paternal hostility (4.5 years) contributed to impairments in math but not reading (7 years), via impacts on ADHD symptoms (6 years). Conclusion: Findings highlight the importance of early child behavior dysregulation evoking parent hostility in both mothers and fathers, with maternal and paternal hostility contributing to the continuation of ADHD symptoms and lower levels of later math ability. Early interventions may be important for the promotion of child math skills in those with ADHD symptoms, especially where children have high levels of early behavior dysregulation

Enhancing the utility of antroduodenal manometry in pediatric intestinal pseudo-obstruction

BACKGROUND: Antroduodenal manometry (ADM) and histopathology are currently employed to aid the diagnosis of pediatric intestinal pseudo-obstruction (PIPO). Limited data are available on the reliability of ADM analysis and its correlation with histopathology. We aimed to develop a protocol for enhanced analysis of ADM contractile patterns, including a scoring system, and explore whether this provided better correlation with histopathology. METHODS: Children referred with suspected PIPO between April 2012-December 2019 who underwent both ADM and full-thickness biopsies were included. ADM tracings were analyzed using both standard (conventional ADM) and novel (enhanced ADM) motility parameters. A novel ADM score (GLASS score) was generated based on the enhanced ADM analysis. Conventional and enhanced ADM analyses were then correlated with histopathology. RESULTS: Forty patients were included. Using conventional clinical criteria, 29 of these were diagnosed with PIPO and the other 11 with non-PIPO diagnoses. Twenty-three of the PIPO patients had abnormal histopathology: 6 myopathy, 4 neuropathy, 3 neuro-myopathy, and 10 non-specific changes. No agreement in diagnosis was found between conventional ADM analysis and histopathology (ϰ = 0.068; p = 0.197), whereas the latter significantly correlated with enhanced ADM analysis (ϰ = 0.191; p = 0.003). The enhanced ADM score was significantly higher in PIPO versus non-PIPO (16.0 vs. 8.0; p < 0.001). CONCLUSIONS: As opposed to conventional analysis protocols, the newly developed enhanced ADM analysis and associated score is not only able to discriminate between PIPO and non-PIPO patients, but also between distinct histopathological pathologies. Further studies are required to assess the utility of enhanced ADM analysis in larger populations

Is there a relationship between joint hypermobility and gastrointestinal disorders in children?

Background. The main aim of the study was to assess the association between joint hypermobility (JH) and gastrointestinal (GI) disorders in children. Methods. All children aged 4-17 years attending the clinics of the participating Pediatric Gastroenterology Centres for functional GI disorders (FGIDs) and inflammatory bowel disease (IBD) were screened for joint laxity. JH diagnosis was inferred using the Beighton Score. JHS diagnosis was inferred based on the Brighton Criteria. Rome III Diagnostic Criteria were used to diagnose possible FGIDs. Ulcerative colitis and Crohn’s disease diagnoses were made according to the Porto Criteria. Age and sex- matched healthy children were enrolled as controls. Results. One-hundred-seventy children with GI disorders (70 with FGIDs, 50 with Crohn’s disease, and 50 with ulcerative colitis) and 100 healthy controls were enrolled in the study. JH was reported in 7/70 (10%) children with FGIDs (p=0.26 compared to controls), 4/50 (8%) children with Crohn’s disease (p=0.21 compared to controls) and 15/50 (30%) children with ulcerative colitis (p=0.09 compared to controls; p=0.01 compared to FGIDs; p=0.01 compared to Crohn’s). Conclusions. JH is more prevalent in patients suffering from ulcerative colitis compared to the healthy general population, yet the difference did not reach statistical significance. Likely, a proportion of children with ulcerative colitis and JH may show connective tissue abnormalities. However, whether JH can be considered a possible feature of pediatric GI disorders deserves further investigation

Compression hosiery to avoid post-thrombotic syndrome (CHAPS) protocol for a randomised controlled trial (ISRCTN73041168).

INTRODUCTION: Up to 50% of patients develop post-thrombotic syndrome (PTS) after an above knee deep vein thrombosis (DVT). The aim of the study was to determine the effect of graduated compression stockings in preventing PTS after DVT. METHODS AND ANALYSIS: Pragmatic, UK multicentre randomised trial in adults with first above knee DVT. The standard of care arm is anticoagulation. The intervention arm will receive anticoagulation plus stockings (European class II, 23-32 mm Hg compression) worn for a median of 18 months. The primary endpoint is PTS using the Villalta score. Analysis of this will be through a time to event approach and cumulative incidence at median 6, 12 and 18 months. An ongoing process evaluation will examine factors contributing to adherence to stockings to understand if and how the behavioural interventions were effective. ETHICS AND DISSEMINATION: UK research ethics committee approval (reference 19/LO/1585). Dissemination though the charity Thrombosis UK, the Imperial College London website, peer-reviewed publications and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN registration number 73041168

Using a genetically informative design to examine the relationship between breastfeeding and childhood conduct problems

A number of public health interventions aimed at increasing the uptake of breastfeeding are in place in the United States and other Western countries. While the physical health and nutritional benefits of breastfeeding for the mother and child are relatively well established, the evidence for psychological effects is less clear. This study aimed to examine whether there is an association between breastfeeding and later conduct problems in children. It also considered the extent to which any relationship is attributable to maternally-provided inherited characteristics that influence both likelihood of breastfeeding and child conduct problems. A prenatal cross-fostering design with a sample of 870 families with a child aged 4–11 years was used. Mothers were genetically related or unrelated to their child as a result of assisted reproductive technologies. The relationship between breastfeeding and conduct problems was assessed while controlling for theorised measured confounders by multivariate regression (e.g. maternal smoking, education, and antisocial behaviour), and for unmeasured inherited factors by testing associations separately for related and unrelated mother-child pairs. Breastfeeding was associated with lower levels of conduct disorder symptoms in offspring in middle childhood. Breastfeeding was associated with lower levels of conduct problems even after controlling for observed confounders in the genetically related group, but not in the genetically unrelated group. In contrast, maternal antisocial behaviour showed robust associations with child conduct problems after controlling for measured and inherited confounders. These findings highlight the importance of using genetically sensitive designs in order to test causal environmental influences

The links between prenatal stress and offspring development and psychopathology: disentangling environmental and inherited influences

Background. Exposure to prenatal stress is associated with later adverse health and adjustment outcomes. This is generally presumed to arise through early environmentally mediated programming effects on the foetus. However, associations could arise through factors that influence mothers’ characteristics and behaviour during pregnancy which are inherited by offspring. Method. A ‘ prenatal cross-fostering ’ design where pregnant mothers are related or unrelated to their child as a result of in vitro fertilization (IVF) was used to disentangle maternally inherited and environmental influences. If links between prenatal stress and offspring outcome are environmental, association should be observed in unrelated as well as related mother–child pairs. Offspring birth weight and gestational age as well as mental health were the outcomes assessed. Results. Associations between prenatal stress and offspring birth weight, gestational age and antisocial behaviour were seen in both related and unrelated mother–offspring pairs, consistent with there being environmental links. The association between prenatal stress and offspring anxiety in related and unrelated groups appeared to be due to current maternal anxiety/depression rather than prenatal stress. In contrast, the link between prenatal stress and offspring attention deficit hyperactivity disorder was only present in related mother–offspring pairs and therefore was attributable to inherited factors. Conclusions. Genetically informative designs can be helpful in testing whether inherited factors contribute to the association between environmental risk factors and health outcomes. These results suggest that associations between prenatal stress and offspring outcomes could arise from inherited factors and post-natal environmental factors in addition to causal prenatal risk effects

Effects of low birth weight, maternal smoking in pregnancy and social class on the phenotypic manifestation of Attention Deficit Hyperactivity Disorder and associated antisocial behaviour: investigation in a clinical sample

<p>Abstract</p> <p>Background</p> <p>Attention Deficit Hyperactivity Disorder (ADHD) is a genetically influenced condition although indicators of environmental risk including maternal smoking during pregnancy, low birth weight and low social class have also been found to be associated with the disorder.</p> <p>ADHD is a phenotypically heterogeneous disorder in terms of the predominant symptom types (inattention, hyperactive-impulsivity), their severity and comorbidity, notably Conduct Disorder. It is possible that these different clinical manifestations of the disorder may arise because of the differing effects of the environmental indicators of environmental risk. We set out to test this hypothesis.</p> <p>Methods</p> <p>In a sample of 356 children diagnosed with ADHD, we sought to investigate possible effects of three indicators of environmental risk – maternal smoking during pregnancy, birth weight and social class – on comorbid Conduct Disorder, conduct disorder symptoms and inattentive and hyperactive-impulsive symptom severity.</p> <p>Results</p> <p>Multiple regression analysis revealed that, after controlling for significant covariates, greater hyperactive-impulsive symptom severity was significantly associated with maternal smoking during pregnancy (r²= 0.02, Beta = 0.11, t = 1.96, p = 0.05) and social class (r²= 0.02, Beta = 0.12, t = 2.19, p = 0.03) whilst none of the environmental risk indicators significantly predicted number of inattentive symptoms. Conduct Disorder symptoms were positively predicted by maternal smoking in pregnancy (r²= 0.04, Beta = 0.18, t = 3.34, p = 0.001) whilst both maternal smoking during pregnancy and social class significantly predicted a diagnosis of Conduct Disorder (OR = 3.14, 95% CI: 1.54, 6.41, Wald = 9.95, p = 0.002) and (OR = 1.95 95% CI: 1.18, 3.23 Wald = 6.78, p = 0.009) respectively.</p> <p>Conclusion</p> <p>These findings suggest that indicators of environmental risk, in this instance maternal smoking in pregnancy and environmental adversity indexed by lower social class, independently influence the clinical presentation of the ADHD phenotype. Other types of study design are needed to investigate whether these associations between indicators of environmental risk factors and ADHD clinical heterogeneity are attributable to causal risk effects and to further establish the magnitude of these effects. These findings have implications, not only for our understanding of the aetiology of ADHD, but may also be of clinical value, enabling the identification of individuals who are at higher risk of problematic behaviours in ADHD, notably conduct disorder, to enable earlier, targeted risk reduction strategies.</p

The genetic architecture of neuroticism in 3301 Dutch adolescent twins as a function of age and sex: a study from the Dutch Twin Register

The objective of this study was to estimate the magnitude of genetic and environmental influences to variation in adolescent neuroticism as a function of age and sex. Neuroticism was assessed using the Amsterdamse Biografische Vragenlijst (ABV): a self-report personality instrument similar in content to the Eysenck Personality Questionnaire. Genetic modeling procedures, including age as modifier, were fitted to the total sample of 3301 Dutch adolescent twins aged 12 to 17 years (mean age 15.5). Significant influences of additive genetic factors (.59, 95% confidence intervals [CI] .54–.63) and unshared environmental factors (.41, 95% CI .37–.45) were found. Our data did not support a role of shared environment. Results showed that different genes may influence variation in neuroticism between girls and boys. No interaction was found between the variance components and age. Results generally support prior findings in adults and young children that neuroticism is influenced principally by additive genetic and unique environmental factors. The magnitude of the genetic component appears higher in the present sample of adolescents than in most studies of adults. The present study suggests that, in adolescence, different genes are expressed in boys and girls