Bacterial carriage in infancy: Risk factors and consequences - The Generation R Study

In this thesis various studies on the prevalence, risk factors and consequences of carriage of Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus in young children are presented. These bacteria are considered important (airway) pathogens in this age group. The definition of pathogen needs further explanation, since the boundary between commensal organisms and pathogenic organisms is not always obvious. According to Casadevall and Pirofski, defining a pathogen as an organism that causes disease in a host is inadequate because some pathogens do not cause disease in all human hosts. The adjective opportunistic is used for pathogens that cause disease only in hosts that are immunocompromised or whose pathogenesis is facilitated by traumatic breaching of an epithelial barrier. For example, about 50% of children two years of age are colonized by S. pneumoniae. This does not lead to disease in most cases, and thus, the pneumococcus can be considered a commensal organism. Weiser et al. have shown that colonization is the natural state of the pneumococcus, and invasive disease, also from the perspective of the pneumococcus, is not favourable. However, S. pneumoniae is the main cause of bacterial otitis media and bacterial pneumonia in young children worldwide. It is also an important cause of life threatening sepsis and meningitis. Moreover, pneumonia is “the leading killer in children”, and since S. pneumoniae is considered to cause more than half the cases of bacterial pneumonia worldwide, it is without any doubt a fearful pathogen

Fetal growth influences lymphocyte subset counts at birth: The generation R study

Background: Preterm born and low-birth-weight infants are at risk for severe infections in infancy. It has been suggested that these infants have an immature immune system. Objective:To assess the associations of gestational age, birth weight and fetal growth with absolute lymphocyte subset counts at birth. Methods: This study was conducted in 571 infants participating in the Generation R Study, a population-based prospective cohort study from fetal life onwards. Gestational age and birth weight were obtained from midwives and hospital registries. Fetal growth was defined as increase in weight between late pregnancy and birth. Lymphocytes and T lymphocyte subset counts in cord blood were determined by 6-color flow cytometry. Multivariate linear regression models with adjustment for gender, maternal education, smoking, alcohol use, fever and mode of delivery were applied. Results: Per week increase of gestational age, T, B and NK lymphocyte counts increased with 3, 5 and 6%, respectively (p < 0.05). Helper, cytotoxic and naive T lymphocyte counts increased with 3, 4 and 5%, respectively (p < 0.05), but memory T lymphocyte counts did not. Increased birth weight and fetal growth were significantly associated with higher B lymphocyte counts, independent of gestational age, but not with the other lymphocyte subset counts. Conclusions: Lymphocyte subset counts increase with prolonged gestation, suggesting an ongoing development of the immune system. Birth weight and fetal growth seem to influence only B lymphocyte counts. Copyrigh

Fulminant cerebral edema as a lethal manifestation of COVID-19

The contribution of neurological symptomatology to morbidity and mortality after infection with Severe Acute Respiratory Syndrome-associated Coronavirus (SARS CoV II) is ill-defined. We hereby present a case of a 57-year old male patient, in excellent physical condition, who was admitted to the Intensive Care Unit (ICU), with respiratory distress duo to SARS Co

Risk factors for otitis media in children with special emphasis on the role of colonization with bacterial airway pathogens: the Generation R study

Acute otitis media is the most frequent diagnosis in children visiting physicians’ offices. Risk factors for otitis media have been widely studied. Yet, the correlation between bacterial carriage and the development of otitis media is not entirely clear. Our aim was to study in a population-based prospective cohort the risk factors for otitis media in the second year of life with special emphasis on the role of colonization with Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. The study was embedded in the Generation R Study. Data on risk factors and doctor-diagnosed otitis media were obtained by midwives, hospital registries and postal questionnaires in the whole cohort (n = 7,295). Nasopharyngeal swabs were obtained at the age of 1.5, 6 and 14 months in the focus cohort (n = 1,079). Of these children, 2,515 (47.2%) suffered at least one period of otitis media in their second year of life. The occurrence of otitis media during the follow-up period in the first 6 months of life and between 6 and 12 months of age was associated with the risk of otitis media in the second year of life (aOR, 1.83 95% CI 1.24–2.71 and aOR 2.72, 95% CI 2.18–3.38, respectively). Having siblings was associated with an increased risk for otitis media in the second year of life (aOR 1.42, 95% CI 1.13–1.79). No associations were found between bacterial carriage in the first year of life and otitis media in the second year of life. In our study, otitis media in the first year of life is an independent risk factor for otitis media in the second year of life. Surprisingly, bacterial carriage in the first year of life did not add to this risk. Moreover, no association was observed between bacterial carriage in the first year of life and otitis in the second year of life

Fetal and infant origins of asthma

Previous studies have suggested that asthma, like other common diseases, has at least part of its origin early in life. Low birth weight has been shown to be associated with increased risks of asthma, chronic obstructive airway disease, and impaired lung function in adults, and increased risks of respiratory symptoms in early childhood. The developmental plasticity hypothesis suggests that the associations between low birth weight and diseases in later life are explained by adaptation mechanisms in fetal life and infancy in response to various adverse exposures. Various pathways leading from adverse fetal and infant exposures to growth adaptations and respiratory health outcomes have been studied, including fetal and early infant growth patterns, maternal smoking and diet, children’s diet, respiratory tract infections and acetaminophen use, and genetic susceptibility. Still, the specific adverse exposures in fetal and early postnatal life leading to respiratory disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life, and their epigenetic mechanisms may underlie the complex associations of low birth weight with respiratory disease in later life. New well-designed epidemiological studies are needed to identify the specific underlying mechanisms. This review is focused on specific adverse fetal and infant growth patterns and exposures, genetic susceptibility, possible respiratory adaptations and perspectives for new studies

The Generation R Study: design and cohort update 2010

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health during fetal life, childhood and adulthood. The study focuses on four primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) diseases in childhood; and (4) health and healthcare for pregnant women and children. In total, 9,778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. General follow-up rates until the age of 4 years exceed 75%. Data collection in mothers, fathers and preschool children included questionnaires, detailed physical and ultrasound examinations, behavioural observations, and biological samples. A genome wide association screen is available in the participating children. Regular detailed hands on assessment are performed from the age of 5 years onwards. Eventually, results forthcoming from the Generation R Study have to contribute to the development of strategies for optimizing health and healthcare for pregnant women and children