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      Pre-Pregnancy Obesity, Excessive Gestational Weight Gain, and the Risk of Pregnancy-Induced Hypertension and Gestational Diabetes Mellitus

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          Abstract

          Excessive pre-pregnancy weight is a known risk factor of pregnancy complications. The purpose of this analysis was to assess the relationship between several categories of maternal weight and the risk of developing hypertension and diabetes in pregnancy, and the relationship of these complications with the results of the newborn. It was carried out in a common cohort of pregnant women and taking into account the influence of disturbing factors. Our analysis was conducted in a prospective cohort of 912 Polish pregnant women, recruited during 2015–2016. We evaluated the women who subsequently developed diabetes with dietary modification (GDM-1) ( n = 125) and with insulin therapy (GDM-2) ( n = 21), as well as the women who developed gestational hypertension (GH) ( n = 113) and preeclampsia (PE) ( n = 24), compared to the healthy controls. Odds ratios of the complications (and confidence intervals (95%)) were calculated in the multivariate logistic regression. In the cohort, 10.8% of the women had pre-pregnancy obesity (body mass index (BMI) ≥ 30 kg/m 2), and 36.8% had gestational weight gain (GWG) above the range of the Institute of Medicine recommendation. After correction for excessive GWG and other confounders, pre-pregnancy obesity (vs. normal BMI) was associated with a higher odds ratio of GH (AOR = 4.94; p < 0.001), PE (AOR = 8.61; p < 0.001), GDM-1 (AOR = 2.99; p < 0.001), and GDM-2 (AOR = 11.88; p <0.001). The threshold risk of development of GDM-2 occurred at lower BMI values (26.9 kg/m 2), compared to GDM-1 (29.1 kg/m 2). The threshold point for GH was 24.3 kg/m 2, and for PE 23.1 kg/m 2. For GWG above the range (vs. GWG in the range), the adjusted odds ratios of GH, PE, GDM-1, and GDM-2 were AOR = 1.71 ( p = 0.045), AOR = 1.14 ( p = 0.803), AOR = 0.74 ( p = 0.245), and AOR = 0.76 ( p = 0.672), respectively. The effect of maternal edema on all the results was negligible. In our cohort, hypertension and diabetes were associated with incorrect birth weight and gestational age at delivery. Conclusions: This study highlights the importance and influence of excessive pre-pregnancy maternal weight on the risk of pregnancy complications such as diabetes and hypertension which can impact fetal outcomes.

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          The Pathophysiology of Gestational Diabetes Mellitus

          Gestational diabetes mellitus (GDM) is a serious pregnancy complication, in which women without previously diagnosed diabetes develop chronic hyperglycemia during gestation. In most cases, this hyperglycemia is the result of impaired glucose tolerance due to pancreatic β-cell dysfunction on a background of chronic insulin resistance. Risk factors for GDM include overweight and obesity, advanced maternal age, and a family history or any form of diabetes. Consequences of GDM include increased risk of maternal cardiovascular disease and type 2 diabetes and macrosomia and birth complications in the infant. There is also a longer-term risk of obesity, type 2 diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5% of pregnancies worldwide, and this number is set to increase with the escalating obesity epidemic. While several management strategies exist—including insulin and lifestyle interventions—there is not yet a cure or an efficacious prevention strategy. One reason for this is that the molecular mechanisms underlying GDM are poorly defined. This review discusses what is known about the pathophysiology of GDM, and where there are gaps in the literature that warrant further exploration.
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            Cardiovascular and Metabolic Heterogeneity of Obesity

            The prevalence of obesity has increased globally over the last 2 decades. Although the body mass index has been a convenient and simple index of obesity at the population level, studies have shown that obesity defined by body mass index alone is a remarkably heterogeneous condition with varying cardiovascular and metabolic manifestations across individuals. Adipose tissue is an exquisitely active metabolic organ engaged in cross-talk between various systems; perturbation of adipose tissue results in a pathological response to positive caloric balance in susceptible individuals that directly and indirectly contributes to cardiovascular and metabolic disease. Inadequate subcutaneous adipose tissue expansion in the face of dietary triglycerides leads to visceral and ectopic fat deposition, inflammatory/adipokine dysregulation, and insulin resistance. Conversely, preferential fat storage in the lower body depot may act as a metabolic buffer and protect other tissues from lipotoxicity caused by lipid overflow and ectopic fat. Translational, epidemiological, and clinical studies over the past 30 years have clearly demonstrated a strong link between visceral and ectopic fat and the development of a clinical syndrome characterized by atherogenic dyslipidemia, hyperinsulinemia/glucose intolerance, hypertension, atherosclerosis, and adverse cardiac remodeling/heart failure. This relationship is even more nuanced when clinical entities such as metabolically healthy obesity phenotype and the obesity paradox are considered. Although it is clear that the accumulation of visceral/ectopic fat is a major contributor to cardiovascular and metabolic risk above and beyond the body mass index, implementation of fat distribution assessment into clinical practice remains a challenge. Anthropometric indexes of obesity are easily implemented, but newer imaging-based methods offer improved sensitivity and specificity for measuring specific depots. Lifestyle, pharmacological, and surgical interventions allow a multidisciplinary approach to overweight/obesity that may improve outcomes and align with a public health message to combat the growing epidemic of obesity worldwide and to build healthier lives free of cardiovascular diseases.
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              Increased Preeclampsia Risk and Reduced Aortic Compliance With In Vitro Fertilization Cycles in the Absence of a Corpus Luteum

              In vitro fertilization involving frozen embryo transfer (FET) and donor oocytes increases preeclampsia risk. These IVF protocols typically yield pregnancies without a corpus luteum (CL), which secretes vasoactive hormones. We investigated whether IVF pregnancies without a CL disrupt maternal circulatory adaptations and increase preeclampsia risk. Women with 0 (n=26), 1 (n=23), or >1 (n=22) CL were serially evaluated before, during and after pregnancy. Because increasing arterial compliance is a major physiological adaptation in pregnancy, we assessed carotid-femoral pulse wave velocity (cfPWV) and transit time (cfPWTT). In a parallel, prospective cohort study, obstetric outcomes for singleton livebirths achieved with autologous oocytes were compared between groups by CL number (n=683). The expected decline in cfPWV and rise in cfPWTT during the first trimester were attenuated in the 0 CL compared to combined single/multiple CL cohorts, which were similar (group-time interaction: p=0.06 and 0.03, respectively). The blunted changes of cfPWV and cfPWTT from pre-pregnancy in the 0 CL cohort were most striking at 10–12 weeks gestation (p=0.01 and 0.006, respectively, versus 1 and >1 CL). 0 CL was predictive of preeclampsia (adjusted odds ratio 2.73; 95%CI 1.14–6.49) and preeclampsia with severe features (6.45; 95%CI 1.94–25.09) compared to 1 CL. Programmed FET cycles (0 CL) were associated with higher rates of preeclampsia (12.8% vs 3.9%, p=0.02) and preeclampsia with severe features (9.6% vs 0.8%, p=0.002) compared with modified natural FET cycles (1 CL). In common IVF protocols, absence of the CL perturbed the maternal circulation in early pregnancy, and increased the incidence of preeclampsia.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                24 June 2020
                June 2020
                : 9
                : 6
                : 1980
                Affiliations
                [1 ]Medical Faculty, Lazarski University, 02-662 Warsaw, Poland
                [2 ]Division of Gynecological Surgery, University Hospital, 33 Polna Str., Poznan University of Medical Sciences, 60-535 Poznan, Poland; ssajdak@ 123456ump.edu.pl
                [3 ]Department of Computer Science and Statistics, Poznan University of Medical Sciences, 60-806 Poznan, Poland; barbara.wieckowska@ 123456ump.edu.pl
                Author notes
                Author information
                https://orcid.org/0000-0001-8613-4955
                Article
                jcm-09-01980
                10.3390/jcm9061980
                7355601
                32599847
                adf6626a-b598-489d-b751-0f2c68785b7e
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 18 May 2020
                : 19 June 2020
                Categories
                Article

                obesity,weight gain,pregnancy,hypertension,preeclampsia,diabetes,overweight,risk

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