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      Parents' depression and loneliness during pregnancy and respiratory infections in the offspring: A prospective birth cohort study

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          Abstract

          Background

          An association between maternal prenatal stress and increased rates of respiratory tract infections in the offspring has been described earlier. Data regarding the father’s role is lacking. In this study our aim was to evaluate, whether mothers’ and fathers’ depressive symptoms and loneliness during pregnancy predict higher rates of respiratory tract infections in the offspring.

          Methods

          In this longitudinal cohort study we gathered information on parental psychological risk during gestational week 20 using the BDI-II and UCLA loneliness scale questionnaires for the parents of 929 children. Loneliness was divided into social and emotional components, the former describing patterns of social isolation and the latter a perceived lack of intimate attachments. Episodes of acute otitis media, physician visits due to respiratory tract infections, and antibiotic consumption relating to respiratory tract infections were documented in the infants, excluding twins, from birth until 10 months of age using study diaries. Analyses were carried out by structural equation modeling, which provides dynamic estimates of covariances.

          Results

          Maternal depressive symptoms during pregnancy predicted higher rates of acute otitis media in the infant and maternal emotional loneliness predicted higher rates of physician visits. Acute otitis media, physician visits and antibiotic consumption in the infant were slightly less frequent for families who reported social loneliness in the father or mother. Associations remained when taking into account confounders.

          Conclusions

          Maternal prenatal depression and emotional loneliness predicted a higher burden of respiratory tract infections in the offspring. The protective influence of parental social loneliness on the burden of respiratory tract infections in infants was not in line with our study hypothesis, but could be explained by reduced use of healthcare services in these socially isolated families.

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          Most cited references22

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          The influence of maternal prenatal and early childhood nutrition and maternal prenatal stress on offspring immune system development and neurodevelopmental disorders

          The developing immune system and central nervous system in the fetus and child are extremely sensitive to both exogenous and endogenous signals. Early immune system programming, leading to changes that can persist over the life course, has been suggested, and other evidence suggests that immune dysregulation in the early developing brain may play a role in neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. The timing of immune dysregulation with respect to gestational age and neurologic development of the fetus may shape the elicited response. This creates a possible sensitive window of programming or vulnerability. This review will explore the effects of maternal prenatal and infant nutritional status (from conception until early childhood) as well as maternal prenatal stress and anxiety on early programming of immune function, and how this might influence neurodevelopment. We will describe fetal immune system development and maternal-fetal immune interactions to provide a better context for understanding the influence of nutrition and stress on the immune system. Finally, we will discuss the implications for prevention of neurodevelopmental disorders, with a focus on nutrition. Although certain micronutrient supplements have shown to both reduce the risk of neurodevelopmental disorders and enhance fetal immune development, we do not know whether their impact on immune development contributes to the preventive effect on neurodevelopmental disorders. Future studies are needed to elucidate this relationship, which may contribute to a better understanding of preventative mechanisms. Integrating studies of neurodevelopmental disorders and prenatal exposures with the simultaneous evaluation of neural and immune systems will shed light on mechanisms that underlie individual vulnerability or resilience to neurodevelopmental disorders and ultimately contribute to the development of primary preventions and early interventions.
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            Prenatal stress, fetal imprinting and immunity.

            A comprehensive number of epidemiological and animal studies suggests that prenatal and early life events are important determinants for disorders later in life. Among them, prenatal stress (i.e. stress experienced by the pregnant mother with impact on the fetal ontogeny) has programming effects on the hypothalamic-pituitary-adrenocortical axis, brain neurotransmitter systems and cognitive abilities of the offspring. This review focuses on the impact of maternal stress during gestation on the immune function in the offspring. It compares results from different animal species and highlights potential mechanisms for the immune effects of prenatal stress, including maternal glucocorticoids and placental functions. The existence of possible windows of increased vulnerability of the immune system to prenatal stress during gestation is discussed. Several gaps in the present knowledge are pointed out, especially concerning the time when prenatal stress effects are expressed during postnatal life, why this expression is delayed after birth and whether prenatal stress predisposes to immune-related pathologies later in life.
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              Stress during Pregnancy and Offspring Pediatric Disease: A National Cohort Study

              Background: Identifying risk factors for adverse health outcomes in children is important. The intrauterine environment plays a pivotal role for health and disease across life. Objectives: We conducted a comprehensive study to determine whether common psychosocial stress during pregnancy is a risk factor for a wide spectrum of pediatric diseases in the offspring. Methods: The study was conducted using prospective data in a population-based sample of mothers with live singleton births (n = 66,203; 71.4% of those eligible) from the Danish National Birth Cohort. We estimated the association between maternal stress during pregnancy (classified based on two a priori–defined indicators of common stress forms, life stress and emotional stress) and offspring diseases during childhood (grouped into 16 categories of diagnoses from the International Classification of Diseases, 10th Revision, based on data from national registries), controlling for maternal stress after pregnancy. Results: Median age at end of follow-up was 6.2 (range, 3.6–8.9) years. Life stress (highest compared with lowest quartile) was associated with an increased risk of conditions originating in the perinatal period [odds ratio (OR) = 1.13; 95% confidence interval (CI): 1.06, 1.21] and congenital malformations (OR=1.17; CI: 1.06, 1.28) and of the first diagnosis of infection [hazard ratio (HR) = 1.28; CI: 1.17, 1.39], mental disorders (age 0–2.5 years: HR = 2.03; CI: 1.32, 3.14), and eye (age 0–4.5 years: HR = 1.27; CI: 1.06, 1.53), ear (HR = 1.36; CI: 1.23, 1.51), respiratory (HR = 1.27; CI; 1.19, 1.35), digestive (HR = 1.23; CI: 1.11, 1.37), skin (HR = 1.24; CI: 1.09, 1.43), musculoskeletal (HR = 1.15; CI: 1.01–1.30), and genitourinary diseases (HR = 1.25; CI; 1.08, 1.45). Emotional stress was associated with an increased risk for the first diagnosis of infection (HR = 1.09; CI: 1.01, 1.18) and a decreased risk for the first diagnosis of endocrine (HR = 0.81; CI; 0.67, 0.99), eye (HR = 0.84; CI; 0.71, 0.99), and circulatory diseases (age 0–3 years: HR = 0.63; CI: 0.42, 0.95). Conclusions: Maternal life stress during pregnancy may be a common risk factor for impaired child health. The results suggest new approaches to reduce childhood diseases.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                7 September 2018
                2018
                : 13
                : 9
                : e0203650
                Affiliations
                [1 ] Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland
                [2 ] Outpatient Clinic for Children and Adolescents, City of Turku, Turku, Finland
                [3 ] Department of Psychology, University of Turku, Turku, Finland
                [4 ] Department of Teacher Education, University of Turku, Turku, Finland
                [5 ] Department of Public Health, University of Turku and Clinical Research Centre, Turku University Hospital, Turku, Finland
                Chiba Daigaku, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-7937-255X
                Article
                PONE-D-17-27158
                10.1371/journal.pone.0203650
                6128609
                30192872
                0af88fe8-09c3-4dc2-b35f-5df0486862cd
                © 2018 Schuez-Havupalo et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 20 July 2017
                : 26 August 2018
                Page count
                Figures: 3, Tables: 2, Pages: 13
                Funding
                Funded by: Academy of Finland
                Award ID: 123571, 140251, and 277535
                Award Recipient :
                Funded by: University of Turku Foundation
                Award Recipient :
                Funded by: TYKS Foundation
                Award Recipient :
                Funded by: Foundation for Pediatric Research
                Award Recipient :
                Funded by: Hospital District of Southwest Finland
                Award Recipient :
                Funded by: City of Turku
                Award Recipient :
                This work was supported by the Academy of Finland, grants 123571, 140251, and 277535; the Foundation for Pediatric Research; research funds from Specified Government Transfers, Hospital District of Southwest Finland and City of Turku. Dr Schuez-Havupalo was supported by the University of Turku Foundation and TYKS Foundation.
                Categories
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                Medicine and Health Sciences
                Mental Health and Psychiatry
                Mood Disorders
                Depression
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                Custom metadata
                Data contain potentially sensitive information. The Clinical Research Centre of the Hospital District of Southwest Finland has specified that legal and ethical restrictions prevent public sharing of deidentified individual participant data. Requests for data are handled by the directory board of the STEPS Study and can be sent to Hanna Lagström ( hanlag@ 123456utu.fi ).

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