Browsing by Subject "MATERNAL OBESITY"

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  • Badeau, Robert M.; Honka, Miikka-Juhani; Bucci, Marco; Iozzo, Patricia; Eriksson, Johan G.; Nuutila, Pirjo (2017)
    Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. The circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: Thirty-seven elderly women were separated into elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using proton nuclear magnetic resonance (1H-NMR) and insulin-dependent tissue-specific glucose uptake in skeletal muscle was assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the docosahexaenoic acid percentage of the total long-chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (p = 0.015). DHA/FA associated significantly with skeletal muscle glucose uptake (GU) (p = 0.031) and the metabolizable glucose value derived from hyperinsulinemic-euglycemic clamp technique (M-value) in the OLM group only (p = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and this association is significantly weakened in the offspring of obese mothers.
  • Lahti-Pulkkinen, Marius; Bhattacharya, Sohinee; Wild, Sarah H.; Lindsay, Robert S.; Räikkönen, Katri; Norman, Jane E.; Bhattacharya, Siladitya; Reynolds, Rebecca M. (2019)
    Aims/hypothesis Maternal obesity in pregnancy is associated with cardiovascular disease and mortality rate in the offspring. We aimed to determine whether maternal obesity is also associated with increased incidence of type 2 and type 1 diabetes in the offspring, independently of maternal diabetes as a candidate mechanistic pathway. Methods Birth records of 118,201 children from 1950 to 2011 in the Aberdeen Maternity and Neonatal Databank were linked to Scottish Care Information-Diabetes, the national register for diagnosed diabetes in Scotland, to identify incident and prevalent type 1 and type 2 diabetes up to 1 January 2012. Maternal BMI was calculated from height and weight measured at the first antenatal visit. The effect of maternal obesity on offspring outcomes was tested using time-to-event analysis with Cox proportional hazards regression to compare outcomes in offspring of mothers in underweight, overweight or obese categories of BMI, compared with offspring of women with normal BMI. Results Offspring of obese (BMI >= 30 kg/m(2)) and overweight (BMI 25-29.9 kg/m(2)) mothers had an increased hazard of type 2 diabetes compared with mothers with normal BMI, after adjustment for gestation when weight was measured, maternal history of diabetes before pregnancy, maternal history of hypertension, age at delivery, parity, socioeconomic status, and sex of the offspring: HR 3.48 (95% CI 2.33, 5.06) and HR 1.39 (1.06, 1.83), respectively. Conclusions/interpretation Maternal obesity is associated with increased incidence of type 2 diabetes in the offspring. Evidence-based strategies that reduce obesity among women of reproductive age and that might reduce the incidence of diabetes in their offspring are urgently required.
  • Eriksson, Johan G. (2019)
    Type 2 diabetes (T2D) is a major, rapidly increasing global public health challenge. The major risk factors for T2D include overweight and obesity, lifestyle-related factors and genetic factors. Early life exposures shape the developmental trajectories and alter susceptibility to T2D. Based on epidemiological studies it has been suggested that fetal undernutrition plays a role in the etiology of T2D. A low birth weight has been considered a proxy for fetal undernutrition. A meta-analysis reported that a 1 kg increase in birth weight is associated with a roughly 20% lower risk of T2D. Although fetal life is of major importance for future health, the period spanning the first 1000 days of life, is characterized by great plasticity and largely influencing later health. Different growth trajectories during this time period have also been associated with an increased risk of T2D. Studies assessing the association between age at BMI rebound in childhood and later risk for T2D have reported a fivefold difference in T2D according to age at BMI rebound. Developmental and epidemiological cohort studies focusing on T2D have major public health implications supporting a paradigm shift; a shift from focusing upon risk factor modification in adult life to adopting a life course perspective when studying T2D. This paradigm shift will not only help us in getting a better understanding of the pathophysiology underlying T2D, but it will also open new possibilities and opportunities in the prevention of T2D and related disorders.
  • Johnson, Linda S. B.; Salonen, Minna; Kajantie, Eero; Conen, David; Healey, Jeff S.; Osmond, Clive; Eriksson, Johan G. (2017)
    Background-Early life risk factors are associated with cardiometabolic disease, but have not been fully studied in atrial fibrillation (AF). There are discordant results from existing studies of birth weight and AF, and the impact of maternal body size, gestational age, placental size, and birth length is unknown. Methods and Results-The Helsinki Birth Cohort Study includes 13 345 people born as singletons in Helsinki in the years 1934-1944. Follow-up was through national registries, and ended on December 31, 2013, with 907 incident cases. Cox regression analyses stratified on year of birth were constructed for perinatal variables and incident AF, adjusting for offspring sex, gestational age, and socioeconomic status at birth. There was a significant U-shaped association between birth weight and AF (P for quadratic term = 0.01). The lowest risk of AF was found among those with a birth weight of 3.4 kg (3.8 kg for women [85th percentile] and 3.0 kg for men [17th percentile]). High maternal body mass index (>= 30 kg/m(2)) predicted offspring AF; hazard ratio 1.36 (95% CI 1.07-1.74, P = 0.01) compared with normal body mass index ( Conclusions-High maternal body mass index during pregnancy and maternal height are previously undescribed predictors of offspring AF. Efforts to prevent maternal obesity might reduce later AF in offspring. Birth weight has a U-shaped relation to incident AF independent of other perinatal variables.
  • Jian, Ching; Carpén, Noora K; Helve, Otto; Vos de, Willem Meindert; Korpela, Katri; Salonen, Anne (2021)
    The colonisation and development of the gut microbiota has been implicated in paediatric metabolic disorders via its powerful effect on host metabolic and immune homeostasis. Here we summarise the evidence from human studies on the early gut microbiota and paediatric overweight and obesity. Manipulation of the early gut microbiota may represent a promising target for countering the burgeoning metabolic disorders in the paediatric population, provided the assembly patterns of microbiota and their health consequences can be decoded. Therefore, in this review, we pay particular attention to the important ecological drivers affecting the community dynamics of the early gut microbiota. We then discuss the knowledge gaps in commonly studied exposures linking the gut microbiota to metabolic disorders, especially regarding maternal factors and antibiotic use. This review also attempts to give directions for future studies aiming to identify predictive and corrective measures for paediatric metabolic disorders based on the gut microbiota.
  • Huovinen, Ville; Bucci, Marco; Lipponen, Heta; Kiviranta, Riku; Sandboge, Samuel; Raiko, Juho; Koskinen, Suvi; Koskensalo, Kalle; Eriksson, Johan G.; Parkkola, Riitta; Iozzo, Patricia; Nuutila, Pirjo (2016)
    Bone marrow insulin sensitivity may be an important factor for bone health in addition to bone mineral density especially in insulin resistant conditions. First we aimed to study if prenatal maternal obesity plays a role in determining bone marrow insulin sensitivity in elderly female offspring. Secondly we studied if a four-month individualized resistance training intervention increases bone marrow insulin sensitivity in elderly female offspring and whether this possible positive outcome is regulated by the offspring's mother's obesity status. 37 frail elderly females (mean age 71.9 +/- 3.1 years) of which 20 were offspring of lean/normal-weight mothers (OLM, maternal BMI = 28.1 kg/m(2)) were studied before and after a four-month individualized resistance training intervention. Nine age-and sex-matched non-frail controls (maternal BMI
  • Mokkala, Kati; Pellonpera, Outi; Roytio, Henna; Pussinen, Pirkko; Ronnemaa, Tapani; Laitinen, Kirsi (2017)
    Background. Increased intestinal permeability with subsequent metabolic endotoxemia, i.e., elevated circulating levels of bacterial lipopolysaccharide, LPS, has been introduced as a novel initiator of obesity related metabolic disturbances in non-pregnant individuals. The objective was to investigate the extent to which intestinal permeability, measured by serum zonulin concentration, is related to metabolic endotoxemia and metabolic risk markers in overweight pregnant women. Methods. This was a cross-sectional study including 100 pregnant overweight women in early pregnancy. Serum zonulin was analyzed using ELISA, and markers for metabolic endotoxemia (LPS), inflammation (high-sensitive C-reactive protein and glycoprotein acetylation GIyA), glucose metabolism (fasting glucose and insulin), and lipid metabolism were measured. Results. Higher serum zonulin concentration associated positively with LPS (P = 0.02), inflammatory markers (P <0.001), insulin (P <0.001), insulin resistance (P <0.001), and triglycerides (P = 0.001), and negatively with insulin sensitivity (P = 0.001) (ANOVA with Tukey's corrections or Kruskal-Wallis nonparametric test with Bonferroni correction for zonulin quartiles). All the observed associations were confirmed (P <0.015) in a linear regression model adjusted with potential confounding factors. Both LPS and GlycA showed positive relationship with insulin resistance, serum insulin, triglycerides, total and LDL-cholesterol and negative relationship with insulin sensitivity (P Conclusions. Our findings suggest that increased serum zonulin concentration, i.e., increased intestinal permeability, contributes to metabolic endotoxemia, systemic inflammation, and insulin resistance in overweight pregnant women. By reinforcingintestinal barrier, it may be possible to manipulate maternal metabolism during pregnancy with subsequent health benefits. (C) 2017 Elsevier Inc. All rights reserved.
  • Abbade, Joelcio; Klemetti, Miira; Farrell, Abby; Ermini, Leonardo; Gillmore, Taylor; Sallais, Julien; Tagliaferro, Andrea; Post, Martin; Caniggia, Isabella (2020)
    IntroductionGestational diabetes mellitus (GDM), a common pregnancy disorder, increases the risk of fetal overgrowth and later metabolic morbidity in the offspring. The placenta likely mediates these sequelae, but the exact mechanisms remain elusive. Mitochondrial dynamics refers to the joining and division of these organelles, in attempts to maintain cellular homeostasis in stress conditions or alterations in oxygen and fuel availability. These remodeling processes are critical to optimize mitochondrial function, and their disturbances characterize diabetes and obesity.Methods and resultsHerein we show that placental mitochondrial dynamics are tilted toward fusion in GDM, as evidenced by transmission electron microscopy and changes in the expression of key mechanochemical enzymes such as OPA1 and active phosphorylated DRP1. In vitro experiments using choriocarcinoma JEG-3 cells demonstrated that increased exposure to insulin, which typifies GDM, promotes mitochondrial fusion. As placental ceramide induces mitochondrial fission in pre-eclampsia, we also examined ceramide content in GDM and control placentae and observed a reduction in placental ceramide enrichment in GDM, likely due to an insulin-dependent increase in ceramide-degrading ASAH1 expression.ConclusionsPlacental mitochondrial fusion is enhanced in GDM, possibly as a compensatory response to maternal and fetal metabolic derangements. Alterations in placental insulin exposure and sphingolipid metabolism are among potential contributing factors. Overall, our results suggest that GDM has profound impacts on placental mitochondrial dynamics and metabolism, with plausible implications for the short-term and long-term health of the offspring.
  • Hautala, Johanna; Gissler, Mika; Ritvanen, Annukka; Helle, Emmi; Pihkala, Jaana; Mattila, Ilkka P.; Pätilä, Tommi; Salminen, Jukka; Puntila, Juha; Jokinen, Eero; Räsänen, Juha; Vahlberg, Tero; Ojala, Tiina (2020)
    Introduction Newborn infants with transposition of the great arteries (d-TGA) need immediate care for an optimal outcome. This study comprised a nationwide 11-year population-based cohort of d-TGA infants, and assessed whether the implementation of a nationwide systematic fetal screening program, or other perinatal, or perioperative factors, are associated with mortality or an increased need for hospital care. Material and methods The national cohort consisted of all live-born infants with simple d-TGA (TGA +/- small ventricular septal defect, n = 127) born in Finland during 2004-2014. Data were collected from six national registries. Prenatal diagnosis and perinatal and perioperative factors associated with mortality and length of hospitalization were evaluated. Results Preoperative mortality was 7.9%, and the total mortality was 8.7%. The prenatal detection rate increased after introducing systematic fetal anomaly screening from 5.0% to 37.7% during the study period (P <.0001), but the total mortality rate remained unchanged. All prenatally diagnosed infants (n = 27) survived. Lower gestational age (odds ratio 0.68,P = .012) and higher maternal age at birth (odds ratio 1.16,P = .036) were associated with increased mortality in multivariable analysis. Older infant age at time of operation (P = .002), longer aortic clamp time (P <.001), and higher maternal body mass index (P = .027) were associated with longer initial hospital stay. An extended need for hospital care during the first year of life was multi-factorial. Conclusions In our cohort, none of the prenatally diagnosed d-TGA infants died. As a result of the limited prenatal detection rates, however, the sample size was insufficient to reach statistical significance. The d-TGA infants born with lower gestational age and to older mothers had increased mortality.
  • Rönö, Kristiina; Stach-Lempinen, Beata; Eriksson, Johan Gunnar; Pöyhönen-Alho, Maritta; Klemetti, Miira Marjuska; Roine, Risto Paavo; Huvinen, Emilia; Andersson, Sture; Laivuori, Hannele; Valkama, Anita; Meinilä, Jelena; Kautiainen, Hannu; Tiitinen, Aila; Koivusalo, Saila Birgitta (2018)
    Purpose: Lifestyle intervention studies performed during pregnancy have shown inconsistent results in relation to prevention of gestational diabetes mellitus (GDM). Therefore, the aim of this study was to assess the effect of an intervention initiated already before pregnancy in prevention of GDM in high-risk women. Patients and methods: A randomized controlled trial was conducted in four Finnish maternity hospitals between the years 2008 and 2014. Altogether 228 high-risk women planning pregnancy were randomized to an intervention (n=116) or a control group (n=112). The risk factors were body mass index >= 30 kg/m(2) (n=46), prior GDM (n=120), or both (n=62), without manifest diabetes at study inclusion. Trained study nurses provided individualized lifestyle counseling every 3 months in addition to a group session with a dietician. The control group received standard antenatal care. GDM was defined as one or more pathological glucose values in a 75 g 2-hour oral glucose tolerance test, performed between 12 and 16 weeks of gestation and if normal repeated between 24 and 28 weeks of gestation. Results: Within 12 months, 67% of the women (n=72) in the intervention group and 63% of the women (n=71) in the control group (p=0.84) became pregnant. The cumulative incidence of GDM among the women available for the final analyses was 60% (n=39/65) in the intervention group and 54% (n=34/63) in the control group (p=0.49). GDM was diagnosed already before 20 weeks of gestation in 60% (n=44/73) of the cases. Conclusion: The preconceptional lifestyle intervention applied in the present study did not reduce the incidence of GDM.
  • Hautala, J.; Gissler, M.; Ritvanen, A.; Tekay, A.; Pitkänen-Argillander, O.; Stefanovic, V.; Sarkola, T.; Helle, E.; Pihkala, J.; Pätilä, T.; Mattila, I. P.; Jokinen, E.; Räsänen, J.; Ojala, T. (2019)
    Objective To evaluate whether a nationwide prenatal anomaly screening programme improves detection rates of univentricular heart (UVH) and transposition of great arteries (TGA), and whether maternal risk factors for severe fetal heart disease affect prenatal detection. Design Population-based cohort study. Setting Nationwide data from Finnish registries 2004-14. Population A total of 642 456 parturients and 3449 terminated pregnancies due to severe fetal anomaly. Methods Prenatal detection rates were calculated in three time periods (prescreening, transition and screening phase). The effect of maternal risk factors (obesity, in vitro fertilisation, pregestational diabetes and smoking) was evaluated. Main outcome measures Change in detection rates and impact of maternal risk factors on screening programme efficacy. Results In total, 483 cases of UVH and 184 of TGA were detected. The prenatal detection rate of UVH increased from 50.4% to 82.8% and of TGA from 12.3% to 41.0% (P <0.0001). Maternal risk factors did not affect prenatal detection rate, but detection rate differed substantially by region. Conclusions A nationwide screening programme improved overall UVH and TGA detection rates, but regional differences were observed. Obesity or other maternal risk factors did not affect the screening programme efficacy. The establishment of structured guidelines and recommendations is essential when implementing the screening programme. In addition, a prospective screening register is highly recommended to ensure high quality of screening.