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  • Masalin, Senja; Rönö, Kristiina; Kautiainen, Hannu; Gissler, Mika; Eriksson, Johan G.; Laine, Merja K. (2019)
    AimsTo assess the relationship between body surface area (BSA) at birth and future risk for gestational diabetes mellitus (GDM).MethodsThis is an observational cohort study from Vantaa, Finland. The cohort included 1548 Finnish primiparous women, aged 15-28 years, without pre-existing diabetes, who gave birth 2009-2015. All women were born full-term and had complete information about their birth weight and length, from the Finnish Medical Birth Register. Additional data for the study were provided by individual patient health records and Statistics Finland. Study participants were divided into five levels (I-V) according to BSA at birth, based on normal distribution.ResultsThere was an inverse association between BSA at birth and risk for GDM (p=0.015 for linearity, after adjustments for age, educational attainment, pre-pregnancy BMI and smoking). The odds ratio (OR) for GDM in level V, with the largest BSA at birth, compared with level I, with the smallest BSA at birth, was 0.43 [95% confidence interval (CI) 0.22-0.83]; adjusted for age, educational attainment, pre-pregnancy body mass index and smoking. The OR for GDM was 0.8 (95% CI 0.68-0.95, p=0.009) for each one standard deviation increase in BSA at birth, adjusted for the same confounders. BSA at birth correlated with adult anthropometry: correlation coefficients were r=0.16 (95% CI 0.11-0.21) for weight, r=0.31 (95% CI 0.26-0.35) for height, and r=0.06 (95% CI 0.01-0.11) for BMI.ConclusionsBody surface area at birth is inversely associated with future risk for GDM in primiparous women.
  • Komulainen, Kaisla; Mittleman, Murray A.; Ruohonen, Saku; Laitinen, Tomi T.; Pahkala, Katja; Elovainio, Marko; Tammelin, Tuija; Kähönen, Mika; Juonala, Markus; Keltikangas-Järvinen, Liisa; Raitakari, Olli; Pulkki-Råback, Laura; Jokela, Markus (2019)
    Introduction: This study used causal mediation analysis to assess the life-course associations of a favorable childhood psychosocial environment with left ventricular mass and diastolic function in adulthood and the extent to which adult health behaviors mediate these associations. Methods: The sample included 880 participants (56% women) from the Young Finns Study with data on the childhood environment from 1980, adult health behaviors (smoking, physical activity, diet, and BMI) from 2001 and an echocardiographic assessment of the left ventricular mass (g/m(2.7)) and diastolic function (E/e' ratio; higher values indicating a lower diastolic function) from 2011. The associations of the childhood environment with the left ventricular mass and E/e' ratio and mediation pathways through health behaviors were assessed using marginal structural models that were controlled for age, sex, and time-dependent confounding by adult socioeconomic position (measured as educational attainment) via inverse probability weighting. The data were analyzed in 2018-2019. Results: The mean age in 2011 was 41 (range 34-49) years. Those above versus below the median childhood score had a 1.28 g/m(2.7) lower left ventricular mass (95% CI = -2.63, 0.07) and a 0.18 lower E/e' ratio (95% CI = -0.39, 0.03). There was no evidence for indirect effects from childhood environments to left ventricular outcomes through adult health behaviors after controlling for time-dependent confounding by the adult socioeconomic position (indirect effect beta = -0.30, 95% CI = -1.22, 0.63 for left ventricular mass; beta = -0.04, 95% CI = -0.18, 0.11 for E/e' ratio). The results after multiple imputation were similar. Conclusions: A favorable childhood environment is associated with more optimal cardiac structure and function in adulthood. After accounting for socioeconomic positions, adult health behaviors explain little of the associations. (C) 2019 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
  • Chen, Jing; Bacelis, Jonas; Sole-Navais, Pol; Srivastava, Amit; Juodakis, Julius; Rouse, Amy; Hallman, Mikko; Teramo, Kari; Melbye, Mads; Feenstra, Bjarke; Freathy, Rachel M.; Smith, George Davey; Lawlor, Deborah A.; Murray, Jeffrey C.; Williams, Scott M.; Jacobsson, Bo; Muglia, Louis J.; Zhang, Ge (2020)
    Author summaryWhy was this study done? Maternal height, BMI, blood glucose, and blood pressure are associated with gestational duration, birth weight, and birth length. These birth outcomes are subsequently associated with late-onset health conditions. The causal mechanisms and the relative contributions of maternal and fetal genetic effects underlying these observed associations are not clear. What did the researchers do and find? We dissected the relative contributions of maternal and fetal genetic effects using haplotype genetic score analysis in 10,734 mother-infant pairs of European ancestry. Genetically elevated maternal height is associated with longer gestational duration and larger birth size. In the fetus, alleles associated with adult height are positively associated with birth size. Alleles elevating blood pressure are associated with shorter gestational duration through a maternal effect and are associated with reduced fetal growth through a fetal genetic effect. Alleles that increase blood glucose in the mother are associated with increased birth weight, whereas risk alleles for type 2 diabetes in the fetus are associated with reduced birth weight. Alleles raising birth weight in fetus are associated with shorter gestational duration and higher maternal blood pressure during pregnancy. What do these findings mean? Maternal size and fetal growth are important factors in shaping the duration of gestation. Fetal growth is influenced by both maternal and fetal effects. Higher maternal BMI and glucose levels positively associate with birth weight through maternal effects. In the fetus, alleles associated with higher metabolic risks are negatively associated with birth weight. More rapid fetal growth is associated with shorter gestational duration and higher maternal blood pressure. These maternal and fetal genetic effects can largely explain the observed associations between maternal phenotypes and birth outcomes, as well as the life-course associations between these birth outcomes and adult phenotypes. Background Many maternal traits are associated with a neonate's gestational duration, birth weight, and birth length. These birth outcomes are subsequently associated with late-onset health conditions. The causal mechanisms and the relative contributions of maternal and fetal genetic effects behind these observed associations are unresolved. Methods and findings Based on 10,734 mother-infant duos of European ancestry from the UK, Northern Europe, Australia, and North America, we constructed haplotype genetic scores using single-nucleotide polymorphisms (SNPs) known to be associated with adult height, body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), and type 2 diabetes (T2D). Using these scores as genetic instruments, we estimated the maternal and fetal genetic effects underlying the observed associations between maternal phenotypes and pregnancy outcomes. We also used infant-specific birth weight genetic scores as instrument and examined the effects of fetal growth on pregnancy outcomes, maternal BP, and glucose levels during pregnancy. The maternal nontransmitted haplotype score for height was significantly associated with gestational duration (p= 2.2 x 10(-4)). Both maternal and paternal transmitted height haplotype scores were highly significantly associated with birth weight and length (p<1 x 10(-17)). The maternal transmitted BMI scores were associated with birth weight with a significant maternal effect (p= 1.6 x 10(-4)). Both maternal and paternal transmitted BP scores were negatively associated with birth weight with a significant fetal effect (p= 9.4 x 10(-3)), whereas BP alleles were significantly associated with gestational duration and preterm birth through maternal effects (p= 3.3 x 10(-2)andp= 4.5 x 10(-3), respectively). The nontransmitted haplotype score for FPG was strongly associated with birth weight (p= 4.7 x 10(-6)); however, the glucose-increasing alleles in the fetus were associated with reduced birth weight through a fetal effect (p= 2.2 x 10(-3)). The haplotype scores for T2D were associated with birth weight in a similar way but with a weaker maternal effect (p= 6.4 x 10(-3)) and a stronger fetal effect (p= 1.3 x 10(-5)). The paternal transmitted birth weight score was significantly associated with reduced gestational duration (p= 1.8 x 10(-4)) and increased maternal systolic BP during pregnancy (p= 2.2 x 10(-2)). The major limitations of the study include missing and heterogenous phenotype data in some data sets and different instrumental strength of genetic scores for different phenotypic traits. Conclusions We found that both maternal height and fetal growth are important factors in shaping the duration of gestation: genetically elevated maternal height is associated with longer gestational duration, whereas alleles that increase fetal growth are associated with shorter gestational duration. Fetal growth is influenced by both maternal and fetal effects and can reciprocally influence maternal phenotypes: taller maternal stature, higher maternal BMI, and higher maternal blood glucose are associated with larger birth size through maternal effects; in the fetus, the height- and metabolic-risk-increasing alleles are associated with increased and decreased birth size, respectively; alleles raising birth weight in the fetus are associated with shorter gestational duration and higher maternal BP. These maternal and fetal genetic effects may explain the observed associations between the studied maternal phenotypes and birth outcomes, as well as the life-course associations between these birth outcomes and adult phenotypes.
  • Robinson, Rachel; Lahti-Pulkkinen, Marius; Heinonen, Kati; Reynolds, Rebecca M.; Räikkönen, Katri (2019)
    BACKGROUND: Maternal depression complicates a large proportion of pregnancies. Current evidence shows numerous harmful effects on the offspring. Reviews, which include depression, concluded that stress has harmful effects on the offspring's outcomes neuro-cognitive development, temperament traits, and mental disorders. OBJECTIVE: This mini review of recent studies, sought to narrow the scope of exposure and identify studies specifically assessing prenatal depression and offspring neuropsychiatric outcomes. STUDY ELIGIBILITY CRITERIA: The review included longitudinal, cohort, cross-sectional, clinical, quasi-experimental, epidemiological, or intervention study designs published in English from 2014 to 2018. PARTICIPANTS: Study populations included mother-child dyads, mother-father-child triads, mother-alternative caregiver-child triads, and family studies utilizing sibling comparisons. METHODS: We searched PubMED and Web of Science. Study inclusion and data extraction were based on standardized templates. The quality of evidence was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: Thirteen studies examining neuropsychiatric outcomes were included. We judged the evidence to be moderate to high quality. CONCLUSIONS: Our review supports that maternal prenatal depression is associated with neuropsychiatric adversities in children.
  • Hemida, Manal; Vuori, Kristiina A.; Salin, Siru; Moore, Robin; Anturaniemi, Johanna; Hielm-Bjorkman, Anna (2020)
    A cross-sectional hypothesis generating study was performed to investigate modifiable exposures such as whether feeding pattern (a non-processed meat based diet, NPMD, or an ultra-processed carbohydrate based diet, UPCD), certain environmental factors and their timing of exposure might be associated with the development of canine atopic dermatitis (CAD). Also, genetic and demographic factors were tested for associations with CAD. The data was collected from the validated internet-based DogRisk food frequency questionnaire in Finland. A total of 2236 dogs were eligible for the study (the owners reported 406 cases and 1830 controls). Our main interest was to analyze modifiable early risk factors of CAD, focusing on nutritional and environmental factors. We tested four early life periods; prenatal, neonatal, early postnatal and late postnatal periods. Twenty-two variables were tested for associations with CAD using logistic regression analysis. From the final models we identified novel dietary associations with CAD: the NPMD during the prenatal and early postnatal periods had a significant negative association with the incidence of CAD in adult dogs (age above 1 year). Oppositely, UPCD was associated with a significantly higher risk for CAD incidence. Other variables that were associated with a significantly lower risk for CAD were maternal deworming during pregnancy, sunlight exposure during early postnatal period, normal body condition score during the early postnatal period, the puppy being born within the same family that it would stay in, and spending time on a dirt or grass surface from 2 to 6 months. Also, the genetic factors regarding maternal history of CAD, allergy-prone breeds and more than 50% white-colored coat all showed a significant positive association with CAD incidence in agreement with previous findings. Although no causality can be established, feeding NPMD early in life seemed to be protective against CAD, while UPCD could be considered a risk factor. Prospective intervention studies are needed to establish the causal effects of the protective role of NPMD on prevalence of CAD during the fetal and early postnatal life.
  • Pirilä, Satu Maaria; Taskinen, Mervi; Viljakainen, Heli; Kajosaari, Merja; Turanlahti, Maila; Saarinen-Pihkala, Ulla M.; Mäkitie, Outi (2011)
  • Lahti-Pulkkinen, Marius; Räikkönen, Katri; Bhattacharya, Sohinee; Reynolds, Rebecca M. (2021)
    Maternal obesity in pregnancy predicts offspring psychopathology risk in childhood but it remains unclear whether maternal obesity or underweight associate with adult offspring mental disorders. We examined longitudinally whether maternal body mass index (BMI) in pregnancy predicted mental disorders in her offspring and whether the associations differed by offspring birth year among 68,571 mother–child dyads of Aberdeen Maternity and Neonatal Databank, Scotland. The offspring were born 1950–1999. Maternal BMI was measured at a mean 15.7 gestational weeks and classified into underweight, normal weight, overweight, moderate obesity and severe obesity. Mental disorders were identified from nationwide registers carrying diagnoses of all hospitalizations and deaths in Scotland in 1996–2017. We found that maternal BMI in pregnancy was associated with offspring mental disorders in a time-dependent manner: In offspring born 1950–1974, maternal underweight predicted an increased hazard of mental disorders [Hazard Ratio (HR) = 1.74; 95% Confidence Interval (CI) = 1.01–3.00)]. In offspring born 1975–1999, maternal severe obesity predicted increased hazards of any mental (HR 1.60; 95% CI 1.08–2.38) substance use (HR 1.91; 95% CI 1.03–3.57) and schizophrenia spectrum (HR 2.80; 95% CI 1.40–5.63) disorders. Our findings of time-specific associations between maternal prenatal BMI and adult offspring mental disorders may carry important public health implications by underlining possible lifelong effects of maternal BMI on offspring psychopathology.
  • Lahti, Jari; Lahti, Marius; Pesonen, Anu-Katriina; Heinonen, Kati; Kajantie, Eero; Forsen, Tom; Wahlbeck, Kristian; Osmond, Clive; Barker, David J. P.; Eriksson, Johan G.; Raikkonen, Katri (2014)
  • Eriksson, Johan G.; Salonen, Minna K.; Kajantie, Eero; Osmond, Clive (2018)
    Background: According to the Developmental Origins of Health and Disease (DOHaD) hypothesis, several noncommunicable diseases, including hypertension, type 2 diabetes, and coronary heart disease, have their origins in early life. Chronic kidney disease (CKD) has traditionally been assumed to develop as the result of an interaction between genetic and environmental factors, although more recently, the importance of factors present early in life has been recognized. Study Design: Longitudinal birth cohort study. Setting & Participants: 20,431 people born in 1924 to 1944 in Helsinki, Finland, who were part of the Helsinki Birth Cohort Study were followed up through their life course from birth until death or age 86 years. Predictor: Prenatal growth and socioeconomic factors. Outcomes: Death or hospitalization for CKD. Results: Smaller body size at birth was associated with increased risk for developing CKD. Each standard deviation higher birth weight was associated with an HR for CKD of 0.82 (95% CI, 0.74-0.91; P <0.001). Associations with ponderal index at birth, placental weight, and birth length were also statistically significant (P <0.001, P <0.001, and P = 0.002, respectively), but only among men. Prematurity also predicted increased risk for CKD. Limitations: The study was restricted to people who were born in Helsinki in 1924 to 1944. Conclusions: Smaller body size at birth was associated with increased risk for developing CKD in men. Prematurity was also associated with increased risk for CKD in women. These findings in the Helsinki Birth Cohort Study support the importance of early life factors in the development of CKD.
  • Maria, Ambika; Nissilä, Ilkka; Shekhar, Shashank; Kotilahti, Kalle; Tuulari, Jetro J.; Hirvi, Pauliina; Huotilainen, Minna; Heiskala, Juha; Karlsson, Linnea; Karlsson, Hasse (2020)
    Background: Maternal pregnancy-related anxiety (PRA) is reportedly related to neurodevelopmental outcomes of infants. However, the relationship between maternal PRA and the processing of emotions in the infant brain has not been extensively studied with neuroimaging. The objective of the present pilot study is to investigate the relationship between maternal PRA and infant hemodynamic responses to emotional speech at two months of age. Methods: The study sample included 19 mother-infant dyads from a general sample of a population of Caucasian mothers. Self-reported Pregnancy-Related Anxiety Questionnaire (PRAQ-R2) data was collected from mothers during pregnancy at gestational weeks (gwks) 24 (N = 19) and 34 (N = 18). When their infants were two months old, the infants' brains functional responses to emotional speech in the left fronto-temporoparietal cortex were recorded using diffuse optical tomography (DOT). Results: Maternal PRAQ-R2 scores at gwk 24 correlated negatively with the total hemoglobin (HbT) responses to sad speech on both sides of the temporoparietal junction (Spearman's rank correlation coefficient rho = -0.87). The correlation was significantly greater at gwk 24 than gwk 34 (rho = -0.42). Limitations: The field of view of the measurement did not include the right hemisphere or parts of the frontal cortex. The sample size is moderate and the mothers were relatively highly educated, thus there may be some differences between the study sample and the general population. Conclusions: Maternal pregnancy-related anxiety may affect child brain emotion processing development. Further research is needed to understand the functional and developmental significance of the findings.
  • Dieckmann, Linda; Cruceanu, Cristiana; Lahti-Pulkkinen, Marius; Lahti, Jari; Kvist, Tuomas; Laivuori, Hannele; Sammallahti, Sara; Villa, Pia M.; Suomalainen-König, Sanna; Rancourt, Rebecca C.; Plagemann, Andreas; Henrich, Wolfgang; Eriksson, Johan G.; Kajantie, Eero; Entringer, Sonja; Braun, Thorsten; Räikkönen, Katri; Binder, Elisabeth B.; Czamara, Darina (2022)
    The placenta is a central organ during early development, influencing trajectories of health and disease. DNA methylation (DNAm) studies of human placenta improve our understanding of how its function relates to disease risk. However, DNAm studies can be biased by cell type heterogeneity, so it is essential to control for this in order to reduce confounding and increase precision. Computational cell type deconvolution approaches have proven to be very useful for this purpose. For human placenta, however, an assessment of the performance of these estimation methods is still lacking. Here, we examine the performance of a newly available reference-based cell type estimation approach and compare it to an often-used reference-free cell type estimation approach, namely RefFreeEWAS, in placental genome-wide DNAm samples taken at birth and from chorionic villus biopsies early in pregnancy using three independent studies comprising over 1000 samples. We found both reference-free and reference-based estimated cell type proportions to have predictive value for DNAm, however, reference-based cell type estimation outperformed reference-free estimation for the majority of data sets. Reference-based cell type estimations mirror previous histological knowledge on changes in cell type proportions through gestation. Further, CpGs whose variation in DNAm was largely explained by reference-based estimated cell type proportions were in the proximity of genes that are highly tissue-specific for placenta. This was not the case for reference-free estimated cell type proportions. We provide a list of these CpGs as a resource to help researchers to interpret results of existing studies and improve future DNAm studies of human placenta.
  • van Best, Niels; Dominguez-Bello, Maria Gloria; Hornef, Mathias W.; Jasarevic, Eldin; Korpela, Katri; Lawley, Trevor D. (2022)