Publications by authors named "Ewa Wender-Ożegowska"

120 Publications

Comparison of Polish and international guidelines on diet supplements in pregnancy - review.

Ginekol Pol 2021 Apr 12. Epub 2021 Apr 12.

Department of Treatment of Obesity, Metabolic Disorders & Clinical Dietetics, Poznan University of Medical Sciences, Poznan, Poland.

Proper nutrition is an important element that determines the course of pregnancy. Unfortunately, the everyday diet is not always able to cover the increased in pregnancy essential vitamins and minerals requirements. Therefore, pregnant women often use dietary supplements. This study aimed to compare Polish and international recommendations regarding dietary supplementation during pregnancy. The Polish Society of Gynaecologists and Obstetricians (PSGO) recommends in every pregnant woman the dietary supplementation of folates, vitamin D and iodine. Additionally, the benefits of iron supplementation in pregnant women with anemia or at high risk of developing anemia are also highlighted. In the light of Polish guidelines, the magnesium supplementation is recommended in the condition of its reduced level in blood. In the case of limited consumption of DHA (docosahexaenoic acid), Polish guidelines recommend in pregnant women's diet, at least 600 mg of DHA every day. Still, in case of the high risk of premature birth - at least 1000 mg DHA a day during the entire pregnancy period should be taken.
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http://dx.doi.org/10.5603/GP.a2021.0001DOI Listing
April 2021

Fetal growth trajectory in type 1 pregestational diabetes (PGDM) - an ultrasound study.

Ginekol Pol 2021 ;92(2):110-117

Department of Reproduction, Chair of Obstertics, Gynecology and Gynecological Oncology, Poznan University of Medical Sciences, Poland, Poland.

Objectives: Growth disorders are frequent in diabetic pregnancies. However, they are difficult to predict and capture early during pregnancy. These newborns are at risk of obesity, diabetes, and cardiovascular disease. While developing, fetal growth abnormalities are typically progressive. Therefore, capturing the earliest moment when they emerge is essential to guide subsequent obstetric management.

Material And Methods: We aimed to analyze fetal ultrasound growth trajectories in type 1 diabetics. Moreover, we aimed to establish time points when first ultrasound manifestations of fetal growth abnormalities appear and to identify factors that affect fetal growth in women with diabetes. We collected clinical and ultrasound data from 200 patients with PGDM managed in the third-referential centre for diabetes in pregnancy. During every visit, patients underwent an ultrasound examination according to a standard protocol giving 1072 ultrasound scan's records. Every ultrasound consisted of fetal weight estimation, according to the Hadlock 3 formula. Retrospectively patients were divided into three groups depending on neonatal weight. In the group of 200 patients, 60 (30%) delivered LGA and 9 (4.5%) SGA newborns.

Results: Fetal growth trajectories show different patterns among fetuses with growth abnormalities in women with type 1 diabetes. The moment, when fetal growth curves diverge, seems to take place in the second trimester, just after the 23rd week of gestation.

Conclusions: It suggests that fetal growth abnormalities in type 1 diabetes may have its roots much earlier than expected. In the first trimester, there were differences in LDL-cholesterol, total cholesterol, triglyceride levels and in insulin requirements between AGA, SGA and LGA subgroups.
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http://dx.doi.org/10.5603/GP.a2020.0136DOI Listing
January 2021

The influence of prepubertal onset of type 1 diabetes and age of menarche on polycystic ovary syndrome diagnosis.

J Clin Endocrinol Metab 2021 Feb 4. Epub 2021 Feb 4.

Department of Internal Medicine and Metabolic Diseases, Medical University of Bialystok, M. Sklodowskiej-Curie, Bialystok, Poland.

Context: Higher prevalence of polycystic ovary syndrome (PCOS) in women with type 1 diabetes (T1DM) is linked to exogenous insulin, especially when diabetes is diagnosed before puberty.

Objective: The study evaluates the impact of prepubertal onset of T1DM and insulin therapy on PCOS diagnosis and phenotypic characteristics in women with T1DM.

Design, Setting And Patients: We studied 83 women with T1DM (age - 26±5 years, BMI - 24±3 kg/m 2) - 36 with premenarchal onset of T1DM (17 with PCOS diagnosed - PCOS+PM, 19 without PCOS - noPCOS+PM) and 47 with postmenarchal onset of T1DM (24 with PCOS - PCOS-noPM and 23 without PCOS - noPCOS-noPM).

Outcome Measurements: Clinical examination, assessment of serum sex hormones, glycated haemoglobin (HbA1c) and ultrasonographic evaluation of the ovaries were performed in all women.

Results: Applying Rotterdam criteria, 49% of women with T1DM were diagnosed with PCOS. There were no differences in hormonal profile and ovarian parameters between PCOS+PM and PCOS-noPM. Women with T1DM+PM had higher insulin dose/24h and U/kg bw/24h than T1DM-noPM (p=0.014; p=0.001, respectively). Both PCOS+PM and noPCOS+PM groups had higher insulin dose U/kg bw/24h in comparison to PCOS-noPM (p=0.004; p=0.006, respectively). In multivariable logistic regression analysis, age of menarche (OR: 0.672; 95% CI: 0.465-0.971) and HbA1c (OR: 0.569; 95% CI: 0.383-0.846) were associated with the diagnosis of PCOS.

Conclusions: There were no differences in the prevalence of PCOS between T1DM+PM and T1DM-noPM; however, earlier menarche might have an influence on PCOS diagnosis in women with T1DM.
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http://dx.doi.org/10.1210/clinem/dgab062DOI Listing
February 2021

The transcriptome-wide association search for genes and genetic variants which associate with BMI and gestational weight gain in women with type 1 diabetes.

Mol Med 2021 01 20;27(1). Epub 2021 Jan 20.

Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Kraków, Poland.

Background: Clinical data suggest that BMI and gestational weight gain (GWG) are strongly interconnected phenotypes; however, the genetic basis of the latter is rather unclear. Here we aim to find genes and genetic variants which influence BMI and/or GWG.

Methods: We have genotyped 316 type 1 diabetics using Illumina Infinium Omni Express Exome-8 v1.4 arrays. The GIANT, ARIC and T2D-GENES summary statistics were used for TWAS (performed with PrediXcan) in adipose tissue. Next, the analysis of association of imputed expression with BMI in the general and diabetic cohorts (Analysis 1 and 2) or GWG (Analysis 3 and 4) was performed, followed by variant association analysis (1 Mb around identified loci) with the mentioned phenotypes.

Results: In Analysis 1 we have found 175 BMI associated genes and 19 variants (p < 10) which influenced GWG, with the strongest association for rs11465293 in CCL24 (p = 3.18E-06). Analysis 2, with diabetes included in the model, led to discovery of 1812 BMI associated loci and 207 variants (p < 10) influencing GWG, with the strongest association for rs9690213 in PODXL (p = 9.86E-07). In Analysis 3, among 648 GWG associated loci, 2091 variants were associated with BMI (FDR < 0.05). In Analysis 4, 7 variants in GWG associated loci influenced BMI in the ARIC cohort.

Conclusions: Here, we have shown that loci influencing BMI might have an impact on GWG and GWG associated loci might influence BMI, both in the general and T1DM cohorts. The results suggest that both phenotypes are related to insulin signaling, glucose homeostasis, mitochondrial metabolism, ubiquitinoylation and inflammatory responses.
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http://dx.doi.org/10.1186/s10020-020-00266-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818927PMC
January 2021

The Role of the Adipokines in the Most Common Gestational Complications.

Int J Mol Sci 2020 Dec 10;21(24). Epub 2020 Dec 10.

Department of Reproduction, Chair of Obstetrics, Gynecology, and Gynecologic Oncology, Poznań University of Medical Sciences, 60-535 Poznan, Poland.

Adipocytokines are hormonally active molecules that are believed to play a key role in the regulation of crucial biological processes in the human body. Numerous experimental studies established significant alterations in the adipokine secretion patterns throughout pregnancy. The exact etiology of various gestational complications, such as gestational diabetes, preeclampsia, and fetal growth abnormalities, needs to be fully elucidated. The discovery of adipokines raised questions about their potential contribution to the molecular pathophysiology of those diseases. Multiple studies analyzed their local mRNA expression and circulating protein levels. However, most studies report conflicting results. Several adipokines such as leptin, resistin, irisin, apelin, chemerin, and omentin were proposed as potential novel early markers of heterogeneous gestational complications. The inclusion of the adipokines in the standard predictive multifactorial models could improve their prognostic values. Nonetheless, their independent diagnostic value is mostly insufficient to be implemented into standard clinical practice. Routine assessments of adipokine levels during pregnancy are not recommended in the management of both normal and complicated pregnancies. Based on the animal models (e.g., apelin and its receptors in the rodent preeclampsia models), future implementation of adipokines and their receptors as new therapeutic targets appears promising but requires further validation in humans.
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http://dx.doi.org/10.3390/ijms21249408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762997PMC
December 2020

Utility of biochemical tests in prediction, diagnostics and clinical management of preeclampsia: a review.

Arch Med Sci 2020 3;16(6):1370-1375. Epub 2020 Aug 3.

Division of Reproduction, Poznan University of Medical Sciences, Poznan, Poland.

The most widely accepted theory for the development of preeclampsia is the "two-stage theory". An imbalance between antiangiogenic and proangiogenic factors is considered the link between the two stages. Nowadays, an increasing amount of data is available on the use of measurements of serum concentrations of these factors in the prediction, diagnosis and management of preeclampsia. The most useful, modern biochemical test that may help in making crucial clinical decisions in patients with preeclampsia is the sFlt-1/PlGF (soluble fms-like tyrosine kinase 1/placental growth factor) ratio. The aim of this review is to present the current use of different biochemical tests in the prediction, diagnosis and management of preeclampsia. Development of these diagnostic methods in recent years and a belief in their ground-breaking role in modern management of preeclampsia make this review especially important.
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http://dx.doi.org/10.5114/aoms.2020.97762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667413PMC
August 2020

Early Screening for Gestational Diabetes Using IADPSG Criteria May Be a Useful Predictor for Congenital Anomalies: Preliminary Data from a High-Risk Population.

J Clin Med 2020 Nov 4;9(11). Epub 2020 Nov 4.

Department of Reproduction, Poznan University of Medical Sciences, 60-512 Poznan, Poland.

Background: Our aim was to investigate whether the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) glycemic thresholds used for detecting hyperglycemia in pregnancy can be predictive for malformations in women with hyperglycemia detected in early pregnancy.

Methods: a single-center, retrospective observational trial of 125 mother-infant pairs from singleton pregnancies with hyperglycemia according to the IADPSG criteria diagnosed at the gestational age below 16 weeks. Glucose values obtained from 75-g OGTT (oral glucose tolerance test) were investigated as predictors for congenital malformations in newborns.

Results: Characteristics of the cohort: maternal age: 31.5 ± 5.2, pre-pregnancy body mass index (BMI) ≥ 30 kg/m: 42.0%, gestational age at diagnosis (weeks): 12.0 ± 4.0, and newborns with congenital malformations: 8.8%. Fasting blood glycemia (FBG) and HbA1c (Haemoglobin A1c) at baseline significantly predicted the outcome (expB: 1.06 (1.02-1.1), = 0.007 and expB: 2.05 (1.24-3.38), = 0.005, respectively). Both the fasting blood glucose (FBG) value of 5.1 mmol/dL (diagnostic for gestational diabetes mellitus (GDM)) and 5.5 mmol/dL (upper limit for normoglycemia in the general population) significantly increased the likelihood ratio (LR) for fetal malformations: 1.3 (1.1; 1.4) and 1.5 (1.0; 2.4), respectively.

Conclusions: (1) Fasting glycemia diagnostic for GDM measured in early pregnancy is associated with a significantly elevated risk for congenital malformations. (2) Our data suggest that women at elevated risks of GDM/diabetes in pregnancy (DiP) should have their fasting blood glucose assessed before becoming pregnant, and the optimization of glycemic control should be considered if the FBG exceeds 5.1 mmol/dL.
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http://dx.doi.org/10.3390/jcm9113553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694288PMC
November 2020

Markers of Endothelial Injury and Dysfunction in Early- and Late-Onset Preeclampsia.

Life (Basel) 2020 Oct 14;10(10). Epub 2020 Oct 14.

Division of Reproduction, Department of Obstetrics, Gynecology, and Gynecologic Oncology, Poznan University of Medical Sciences, 60-535 Poznan, Poland.

With regard to differences in the clinical symptoms of preeclampsia (PE), the degree of endothelial dysfunction may differ between early and late-onset preeclampsia (EOP and LOP). The authors of this study examined it by assessing the endothelial injury level in women with EOP (20 patients) and LOP (20 patients) and in normotensive pregnant women (20 patients) in their late second and third trimesters of pregnancy, using the two markers-the serum concentration of hyaluronan (HA) and the serum level of soluble vascular cell adhesion molecule-1 (sVCAM-1). The serum concentrations of HA and sVCAM-1 did not differ significantly between the EOP and LOP patients. However, these were statistically higher than that of the control group participants ( < 0.05; < 0.001). A significant correlation between the levels of HA and sVCAM-1 was found both in the entire group of patients with preeclampsia ( = 0.0277) and in women with late-onset disease ( = 0.0364), but not in the patients with early-onset preeclampsia ( = 0.331). The obtained results indicated a comparable level of endothelial injury in the two types of PE. The presence of a similar degree of endothelial injury in patients with EOP and LOP should create awareness among all clinicians about the possible fatal complications in both groups of patients with PE.
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http://dx.doi.org/10.3390/life10100239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602169PMC
October 2020

Pregnancy Outcomes in Women with Long-Duration Type 1 Diabetes-25 Years of Experience.

J Clin Med 2020 Oct 8;9(10). Epub 2020 Oct 8.

Department of Reproduction, Poznan University of Medical Sciences, Polna 33, 60-525 Poznań, Poland.

Aims: Our study aimed to examine the pregnancy outcomes (maternal and fetal) concerning different models of antenatal care across a period of over 25 years (1993-2018) in 459 women with type 1 diabetes. Data from patients with a history of the condition lasting at least 15 years were considered eligible for analysis.

Methods: The study group was divided into three cohorts based on the different models of treatment used in Poznan University Hospital, Poland: 1993-2000 (cohort I, = 91), 2001-2005 (cohort II, = 83), 2006-2018 (cohort III, = 284). To identify predictors for the selected dichotomous outcomes, we calculated the risks for fetal or maternal complications as dependent variables for cohorts II and III against cohort I, using multivariate logistic regression analysis.

Results: The mean gestational age was 36.8 ± 2.4 weeks in the total cohort. The percentages of deliveries before the 33rd and the 37th weeks was high. We observed a decreasing percentage during the following periods, from 41.5% in the first period to 30.4% in the third group. There was a tendency for newborn weight to show a gradual increase across three time periods (2850, 3189, 3321 g, < 0.0001). In the last period, we noticed significantly more newborns delivered after 36 weeks with a weight above 4000 g and below 2500 g. Caesarean section was performed in 88% of patients from the whole group, but in the subsequent periods this number visibly decreased (from 97.6%, 86.7%, to 71%, = 0.001). The number of emergency caesarean sections was lowest in the third period (27.5%, 16.7%, 11.2%, = 0.006). We observed a decreasing number of "small for gestational age" newborns (SGA) in consecutive periods of treatment (from 24.4% to 8.7%, = 0.002), but also a higher percentage of "large for gestational age" (LGA) newborns (from 6.1% to 21.6%, = 0.001). Modification of treatment might be associated with the gradual reduction of SGA rates (cohort I 3.6%, cohort III 2.3% < 0,0005).

Conclusions: Strict glycemic and blood pressure control from the very beginning of pregnancy, as well as modern fetal surveillance techniques, may contribute to the improvement of perinatal outcomes in women with long-duration type 1 diabetes.
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http://dx.doi.org/10.3390/jcm9103223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600991PMC
October 2020

Poor glycaemic control contributes to a shift towards prothrombotic and antifibrinolytic state in pregnant women with type 1 diabetes mellitus.

PLoS One 2020 8;15(10):e0237843. Epub 2020 Oct 8.

Department of Reproduction, Chair of Obstetrics, Gynaecology and Oncology, Poznan University of Medical Sciences, Poznan, Poland.

Ojectives: Thrombotic and antifibrinolytic influence of Diabetes mellitus type 1 (T1DM) on haemostasis have been well demonstrated. There has been no research assessing the influence of poor glycemic control on thrombus formation under flow conditions in vitro or in pregnant type 1 diabetic women to date.

Patients/methods: This study compared singleton pregnant T1DM women (n = 21) and control pregnant subjects without any metabolic disease (n = 15). The T1DM group was divided into two subgroups of sufficient (SGC-DM; HbA1c ≤6,5%,n = 15) and poor glycaemic control (PGC-DM; HbA1c >6,5%,n = 6). Evaluation of the whole blood thrombogenicity we assessed using T-TAS® at a shear rate of 240 s-1 (Total-Thrombus Analysis System, Zacros, Japan).

Results: Blood clot formation initiation time (T10) was significantly shortened in PGC-DM subgroup when compared to SGC-DM subgroup (p = 0,03). The area under the curve (AUC30) of blood clot time formation and the MPV (mean platelet volume) values were substantially higher in the PGC-DM subgroup in comparison to the SGC-DM group (p = 0,03). Negative correlations were noted between HbA1c and T10 values (p = 0,02) and between T10 and MPV values in the T1DM group (p = 0,04).

Conclusions: Poor glycaemic control in T1DM subjects triggers a shift towards a prothrombotic and antifibrinolytic state. This phenomenon can be detected using the novel system for quantitative assessment of the platelet thrombus formation process under flow conditions in vitro. The alteration of T-TAS values in PGC-DM subgroup proves that a poor glycemic control-related shift of the equilibrium toward thrombogenesis occurs in this group of patients. Our findings need a further elucidation in research on more massive data sets to be confirmed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237843PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544075PMC
November 2020

Performance of early pregnancy HbA for predicting gestational diabetes mellitus and adverse pregnancy outcomes in obese European women.

Diabetes Res Clin Pract 2020 Oct 21;168:108378. Epub 2020 Aug 21.

Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Public and Occupational Health, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands; Institute of Sport Science, University of Graz, Graz, Austria.

Aims: To investigate the performance of early pregnancy HbA for predicting gestational diabetes mellitus (GDM) and adverse pregnancy outcomes in obese women.

Methods: Post hoc analysis using data from the Vitamin D And Lifestyle Intervention for GDM prevention trials conducted across 9 European countries (2012-2014). Pregnant women (BMI ≥ 29 kg/m) underwent a baseline HbA and oral glucose tolerance tests at < 20 weeks, 24-28 weeks, and 35-37 weeks. Women with GDM were referred for treatment.

Results: Among the 869 women tested, the prevalence of GDM was 25.9% before 20 weeks, with a further 8.6% at 24-28 weeks. The areas under the curves for HbA at the two time points were 0.55 (0.50-0.59) and 0.54 (0.47-0.61), respectively. An early HbA ≥ 5.7% (39 mmol/mol) (N = 111) showed low sensitivity (18.2%) with 89.1% specificity for GDM before 20 weeks, at 24-28 weeks (sensitivity of 8.0% and specificity of 88.6% after excluding early GDM), and throughout gestation (sensitivity of 15.9% and specificity of 89.4%). The ≥ 5.7% (39 mmol/mol) threshold was significantly associated with concurrent GDM before 20 weeks (adjusted OR (aOR) 2.77(1.39-5.51)) and throughout gestation (aOR 1.72 (1.02-2.89)), but not adverse pregnancy outcomes.

Conclusions: Early pregnancy HbA is of limited use for predicting either GDM or adverse outcomes in overweight/obese European women.
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http://dx.doi.org/10.1016/j.diabres.2020.108378DOI Listing
October 2020

Less sedentary time is associated with a more favourable glucose-insulin axis in obese pregnant women-a secondary analysis of the DALI study.

Int J Obes (Lond) 2021 Feb 13;45(2):296-307. Epub 2020 Jul 13.

Institute of Sport Science, University of Graz, Graz, Austria.

Background/objectives: Obese pregnant women are at high risk of developing gestational diabetes mellitus (GDM), which might be reduced by sufficient physical activity (PA) and reduced sedentary time (ST). We assessed whether PA and ST are longitudinally associated with the glucose-insulin axis in obese pregnant women.

Subjects/methods: In this secondary analysis of the DALI (vitamin D And Lifestyle Intervention for gestational diabetes mellitus prevention) study, pregnant women, <20 weeks gestation, with a pre-pregnancy body mass index (BMI) ≥ 29 kg/m, without GDM on entry were included. Time spent in moderate-to-vigorous PA (MVPA) and ST were measured objectively with accelerometers at <20 weeks, 24-28 weeks and 35-37 weeks of gestation. Fasting glucose (mmol/l) and insulin (mU/l), insulin resistance (HOMA-IR) and first-phase and second-phase insulin release (Stumvoll first and second phase) were assessed at the same time. Linear mixed regression models were used to calculate between-participant differences and within-participant changes over time. Analyses were adjusted for gestational age, randomisation, pre-pregnancy BMI, education and age. MVPA, Insulin, HOMA-IR and Stumvoll first and second phase were log-transformed for analyses due to skewness.

Results: 232 women were included in the analysis. Concerning differences between participants, more ST was associated with higher fasting glucose (Estimate: 0.008; 95% CI: 0.002, 0.014), fasting insulin (0.011; 0.002, 0.019), HOMA-IR (0.012; 0.004, 0.021) and Stumvoll first and second phase (0.008; 0.001, 0.014 and 0.007; 0.001, 0.014). Participants with more MVPA had lower Stumvoll first and second phase (-0.137; -0.210, -0.064 and -0.133; -0.202, -0.063). Concerning changes over time, an increase in ST during gestation was associated with elevated Stumvoll first and second phase (0.006; 0.000, 0.011).

Conclusions: As the glucose-insulin axis is more strongly associated with ST than MVPA in our obese population, pregnant women could be advised to reduce ST in addition to increasing MVPA. Moreover, our findings suggest that behaviour change interventions aiming at GDM risk reduction should start in early or pre-pregnancy.
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http://dx.doi.org/10.1038/s41366-020-0639-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840500PMC
February 2021

Mitochondrial GWAS and association of nuclear - mitochondrial epistasis with BMI in T1DM patients.

BMC Med Genomics 2020 07 7;13(1):97. Epub 2020 Jul 7.

Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Kraków, Poland.

Background: BMI is a strong indicator of complications from type I diabetes, especially under intensive treatment.

Methods: We have genotyped 435 type 1 diabetics using Illumina Infinium Omni Express Exome-8 v1.4 arrays and performed mitoGWAS on BMI. We identified additive interactions between mitochondrial and nuclear variants in genes associated with mitochondrial functioning MitoCarta2.0 and confirmed and refined the results on external cohorts: the Framingham Heart Study (FHS) and GTEx data. Linear mixed model analysis was performed using the GENESIS package in R/Bioconductor.

Results: We find a borderline significant association between the mitochondrial variant rs28357980, localized to MT-ND2, and BMI (β = - 0.69, p = 0.056). This BMI association was confirmed on 1889 patients from FHS cohort (β = - 0.312, p = 0.047). Next, we searched for additive interactions between mitochondrial and nuclear variants. MT-ND2 variants interacted with variants in the genes SIRT3, ATP5B, CYCS, TFB2M and POLRMT. TFB2M is a mitochondrial transcription factor and together with TFAM creates a transcription promoter complex for the mitochondrial polymerase POLRMT. We have found an interaction between rs3021088 in MT-ND2 and rs6701836 in TFB2M leading to BMI decrease (inter_pval = 0.0241), while interaction of rs3021088 in MT-ND2 and rs41542013 in POLRMT led to BMI increase (inter_pval = 0.0004). The influence of these interactions on BMI was confirmed in external cohorts.

Conclusions: Here, we have shown that variants in the mitochondrial genome as well as additive interactions between mitochondrial and nuclear SNPs influence BMI in T1DM and general cohorts.
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http://dx.doi.org/10.1186/s12920-020-00752-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341625PMC
July 2020

Evaluation of predictive value of biochemical markers for adverse obstetrics outcomes in pregnancies complicated by cholestasis.

Ginekol Pol 2020;91(5):269-276

Department of Reproduction, Chair of Obstetrics, Gynaecology, and Gynaecological Oncology, Poznan University of Medical Sciences, Poland.

Objectives: Intrahepatic cholestasis of pregnancy (ICP) is significantly more often associated with an abnormal perinatal outcome compared to a group of healthy pregnant women. The aim of the study was to analyse the correlation between the adverse perinatal outcome and the biochemical parameters in pregnancy complicated by cholestasis, and to assess their predictive value for neonatal complications.

Material And Methods: Eighty-six patients with ICP were divided into 3 groups according to their fasting serum bile acid level [group I n = 60, 10-39.90 μmol/L; group II n = 20, 40-99.90 μmol /L; group III n = 6, TBA (total bile acids) ≥ 100.00 μmol/L]. Linear regression models were created to determine the relation of serum TBA, ALT, and AST concentration with total adverse perinatal outcome, defined as an occurrence of at least one perinatal outcome: stillbirth, preterm birth, spontaneous and iatrogenic preterm birth, presence of meconium in amniotic fluid, Apgar score (< 7 in 5th min), pH from umbilical artery (< 7.1), necessity for NICU admission, the presence of breathing disorders, and the need to perform phototherapy.

Results: TBA ≥ 40.00 μmol/L is connected to an elevated risk of the occurrence of total adverse perinatal outcome (OR = 4.17, p = 0.0037, AUC = 0.62, p = 0.046). TBA ≥ 40.00 μmol/L is a predictor of preterm birth (OR 2.3, p = 0.0117), iatrogenic preterm birth (OR 2.5, p = 0.006), admission to NICU (OR 2.38, p = 0.0094), intubation or assisted ventilation (OR 2.16, p = 0.0301), and phototherapy (OR 2.0, p = 0.0438). The threshold value of TBA for the need for phototherapy was 52.7 μmol/L (AUC = 0.67, p = 0.0089) and for preterm birth, 32.1 μmol/L (AUC = 0.62, p = 0.0251).

Conclusions: Pregnant women with ICP and TBA serum level over 40.00 μmol/L have a worse prognosis regarding obstetric outcomes. The concentration of bile acids is a predictor of the occurrence of adverse perinatal outcomes, although the concentration of ALT and AST failed to show such a connection.
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http://dx.doi.org/10.5603/GP.2020.0051DOI Listing
January 2020

Mid-trimester ultrasound parameters for predicting birth weight in low risk pregnancies vs high-risk pregnancies complicated with pre-gestational diabetes mellitus.

Ginekol Pol 2020 ;91(4):216-222

Prenatal Diagnostic Centre, Gynaecology and Obstetrics Hospital, Poznan University of Medical Sciences, Poznan, Poland.

Objectives: The aim of the study was to assess the utility of mid-trimester ultrasound parameters in predicting birth weight in low-risk pregnancy and high-risk pregnancy complicated with pregestational diabetes mellitus.

Material And Methods: A study group comprised 97 healthy women and 160 women with pregestational diabetes (PGDM, type 1), all in singleton pregnancy. Ultrasound examination was performed between weeks 11 and 14, and in weeks 20 and 30 of gestation, based on recommendations of the Polish Society of Gynecologists and Obstetricians, Ultrasonography Division. We also checked uterine artery blood flow parameters.

Results: There is a correlation between the birth weight and ultrasound-ascertained parameters, including those characterising uterine artery blood flow and foetal biometry [abdominal circumference (AC), femoral length (FL), biparietal dimension (BPD)].The biparietal dimension (BPD), head circumference (HC) abdominal circumference (AC) and pre-existing diabetes are the ultrasound predictors of LGA. The presence of an early-diastolic uterine artery blood flow waveform notching, as well as the uterine artery pulsatility index (UAPI), femoral length (FL) and hypertension in pregnancy are the ultrasound predictors of SGA. In the subset of women with pre-gestational diabetes (PGDM), there is a negative correlation between the birth weight and the uterine artery pulsatility index and early-diastolic uterine artery blood flow waveform notching. In women with pre-gestational diabetes mellitus (PGDM), femoral length (FL) is a significant predictor of LGA and in case of SGA significant predictors are uterine artery pulsatility index, artery blood flow waveform notching and femoral length (FL).

Conclusions: Midtrimester ultrasound parameters with confirmed usefulness in the prediction of birth weight in low-risk pregnancy and high-risk pregnancy complicated with pregestational diabetes mellitus include: uterine artery PI, early-diastolic uterine artery blood flow waveform notching and foetal biometry.
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http://dx.doi.org/10.5603/GP.2020.0043DOI Listing
January 2020

The importance of maternal insulin resistance throughout pregnancy on neonatal adiposity.

Paediatr Perinat Epidemiol 2021 Jan 30;35(1):83-91. Epub 2020 Apr 30.

Institution of Sport Science, University of Graz, Graz, Austria.

Background: Although previous studies evaluated the association of maternal health parameters with neonatal adiposity, little is known regarding the complexity of the relationships among different maternal health parameters throughout pregnancy and its impact on neonatal adiposity.

Objectives: To evaluate the direct and indirect associations between maternal insulin resistance during pregnancy, in women with obesity, and neonatal adiposity. In addition, associations between maternal fasting glucose, triglycerides (TG), non-esterified fatty acids (NEFA), and neonatal adiposity were also assessed.

Methods: This is a longitudinal, secondary analysis of the DALI study, an international project conducted in nine European countries with pregnant women with obesity. Maternal insulin resistance (HOMA-IR), fasting glucose, TG, and NEFA were measured three times during pregnancy (<20, 24-28, and 35-37 weeks of gestation). Offspring neonatal adiposity was estimated by the sum of four skinfolds. Structural equation modelling was conducted to evaluate the direct and indirect relationships among the variables of interest.

Results: Data on 657 mother-infant pairs (50.7% boys) were analysed. Neonatal boys exhibited lower mean sum of skinfolds compared to girls (20.3 mm, 95% CI 19.7, 21.0 vs 21.5 mm, 95% CI 20.8, 22.2). In boys, maternal HOMA-IR at <20 weeks was directly associated with neonatal adiposity (β = 0.35 mm, 95% CI 0.01, 0.70). In girls, maternal HOMA-IR at 24-28 weeks was only indirectly associated with neonatal adiposity, which implies that this association was mediated via maternal HOMA-IR, glucose, triglycerides, and NEFA during pregnancy (β = 0.26 mm, 95% CI 0.08, 0.44).

Conclusions: The timing of the role of maternal insulin resistance on neonatal adiposity depends on fetal sex. Although the association was time-dependent, maternal insulin resistance was associated with neonatal adiposity in both sexes.
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http://dx.doi.org/10.1111/ppe.12682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891448PMC
January 2021

Placental Lactogen as a Marker of Maternal Obesity, Diabetes, and Fetal Growth Abnormalities: Current Knowledge and Clinical Perspectives.

J Clin Med 2020 Apr 16;9(4). Epub 2020 Apr 16.

Division of Reproduction, Department of Obstetrics, Gynecology, and Gynecologic Oncology, Poznań University of Medical Sciences, 33 Polna St, 60-535 Poznan, Poland.

Placental lactogen (PL) is a peptide hormone secreted throughout pregnancy by both animal and human specialized endocrine cells. PL plays an important role in the regulation of insulin secretion in pancreatic β-cells, stimulating their proliferation and promoting the expression of anti-apoptotic proteins. Cases of pregnancy affected by metabolic conditions, including obesity and diabetes, are related to alterations in the PL secretion pattern. Whereas obesity is most often associated with lower PL serum concentrations, diabetes results in increased PL blood levels. Disruptions in PL secretion are thought to be associated with an increased prevalence of gestational complications, such as placental dysfunction, diabetic retinopathy, and abnormalities in fetal growth. PL is believed to be positively correlated with birth weight. The impaired regulation of PL secretion could contribute to an increased incidence of both growth retardation and fetal macrosomia. Moreover, the dysregulation of PL production during the intrauterine period could affect the metabolic status in adulthood. PL concentration measurement could be useful in the prediction of fetal macrosomia in women with normal oral glucose tolerance test (OGTT) results or in evaluating the risk of fetal growth restriction, but its application in standard clinical practice seems to be limited in the era of ultrasonography.
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http://dx.doi.org/10.3390/jcm9041142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230810PMC
April 2020

A core outcome set for studies of gestational diabetes mellitus prevention and treatment.

Diabetologia 2020 06 20;63(6):1120-1127. Epub 2020 Mar 20.

School of Medicine, National University of Ireland Galway, Galway, Ireland.

Aims/hypothesis: The aim of this systematic review was to develop core outcome sets (COSs) for trials evaluating interventions for the prevention or treatment of gestational diabetes mellitus (GDM).

Methods: We identified previously reported outcomes through a systematic review of the literature. These outcomes were presented to key stakeholders (including patient representatives, researchers and clinicians) for prioritisation using a three-round, e-Delphi study. A priori consensus criteria informed which outcomes were brought forward for discussion at a face-to-face consensus meeting where the COS was finalised.

Results: Our review identified 74 GDM prevention and 116 GDM treatment outcomes, which were presented to stakeholders in round 1 of the e-Delphi study. Round 1 was completed by 173 stakeholders, 70% (121/173) of whom went on to complete round 2; 84% (102/121) of round 2 responders completed round 3. Twenty-two GDM prevention outcomes and 30 GDM treatment outcomes were discussed at the consensus meeting. Owing to significant overlap between included prevention and treatment outcomes, consensus meeting stakeholders agreed to develop a single prevention/treatment COS. Fourteen outcomes were included in the final COS. These consisted of six maternal outcomes (GDM diagnosis, adherence to the intervention, hypertensive disorders of pregnancy, requirement and type of pharmacological therapy for hyperglycaemia, gestational weight gain and mode of birth) and eight neonatal outcomes (birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, neonatal hypoglycaemia, neonatal death and stillbirth).

Conclusions/interpretation: This COS will enable future GDM prevention and treatment trials to measure similar outcomes that matter to stakeholders and facilitate comparison and combination of these studies.

Trial Registration: This study was registered prospectively with the Core Outcome Measures in Effectiveness Trials (COMET) database: http://www.comet-initiative.org/studies/details/686/.
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http://dx.doi.org/10.1007/s00125-020-05123-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228989PMC
June 2020

Determinants of adiponectin levels during pregnancy in women with type 1 diabetes mellitus.

Pol Arch Intern Med 2020 03 10;130(3):252-254. Epub 2020 Mar 10.

Department of Reproduction, Poznan University of Medical Sciences, Poznań, Poland

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http://dx.doi.org/10.20452/pamw.15227DOI Listing
March 2020

Temporal relationships between maternal metabolic parameters with neonatal adiposity in women with obesity differ by neonatal sex: Secondary analysis of the DALI study.

Pediatr Obes 2020 07 6;15(7):e12628. Epub 2020 Mar 6.

Institute of Sport Science, University of Graz, Graz, Austria.

Objectives: To investigate the importance of time in pregnancy and neonatal sex on the association between maternal metabolic parameters and neonatal sum of skinfolds.

Methods: This was a longitudinal, secondary analysis of the vitamin D and lifestyle intervention for gestational diabetes mellitus study, conducted in nine European countries during 2012 to 2015. Pregnant women with a pre-pregnancy body mass index (BMI) of ≥29 kg/m were invited to participate. We measured 14 maternal metabolic parameters at three times during pregnancy: <20 weeks, 24 to 28 weeks, and 35 to 37 weeks of gestation. The sum of four skinfolds assessed within 2 days after birth was the measure of neonatal adiposity.

Results: In total, 458 mother-infant pairs (50.2% female infants) were included. Insulin resistance (fasting insulin and HOMA-index of insulin resistance) in early pregnancy was an important predictor for boys' sum of skinfolds, in addition to fasting glucose and maternal adiposity (leptin, BMI and neck circumference) throughout pregnancy. In girls, maternal lipids (triglycerides and fatty acids) in the first half of pregnancy were important predictors of sum of skinfolds, as well as fasting glucose in the second half of pregnancy.

Conclusions: Associations between maternal metabolic parameters and neonatal adiposity vary between different periods during pregnancy. This time-dependency is different between sexes, suggesting different growth strategies.
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http://dx.doi.org/10.1111/ijpo.12628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317347PMC
July 2020

Value of cervicovaginal fluid cytokines in prediction of fetal inflammatory response syndrome in pregnancies complicated with preterm premature rupture of membranes (pPROM).

J Perinat Med 2020 Mar;48(3):249-255

Department of Reproduction, Poznan University of Medical Sciences, Poznań, Poland.

Background Preterm premature rupture of membranes (pPROM) is associated with a high risk of prematurity and complications of fetal inflammatory response syndrome (FIRS). The aim of the study is to determine any correlations between the concentration of selected cytokines contained in the cervicovaginal secretion eluates and in the umbilical cord plasma in patients with pPROM and to find the noninvasive markers of FIRS in order to pinpoint the optimal time of the delivery. Methods The study included 80 patients with pPROM between the 24th and 34th week of gestation. The cervicovaginal fluid and umbilical cord blood were collected. Interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 19 (IL-19) and tumor necrosis factor-α (TNF-α) concentrations were measured in both materials. For the statistical analysis, SigmaStat3.5 software was used. Results There was no direct association in levels of IL-6, TNF-α, IL-10 and IL-19 between the cord blood and cervicovaginal secretions within the studied group. The cut-off point of IL-6 of 26.8 pg/mL in the vaginal fluid had high sensitivity and specificity in order to discriminate between newborns with and without FIRS (81.08%; 76.74%). Conclusion Further studies are needed on a larger group of participants to demonstrate that an elevated concentration of IL-6 above 26.8 pg/mL in the cervicovaginal secretion eluate is an indirect noninvasive marker of FIRS.
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http://dx.doi.org/10.1515/jpm-2019-0280DOI Listing
March 2020

The Effects of Lifestyle and/or Vitamin D Supplementation Interventions on Pregnancy Outcomes: What Have We Learned from the DALI Studies?

Curr Diab Rep 2019 12 16;19(12):162. Epub 2019 Dec 16.

Institute of Metabolic Science, Addenbrookes Hospital, Cambridge, England.

Purpose Of Review: The DALI (vitamin D and lifestyle intervention in the prevention of gestational diabetes mellitus (GDM)) study aimed to prevent GDM with lifestyle interventions or Vitamin D supplementation (1600 IU/day). This review summarizes the learnings from the DALI studies among pregnant women with a BMI ≥ 29 kg/m.

Recent Findings: Women diagnosed with GDM earlier in pregnancy had a worse metabolic profile than those diagnosed later. A combined physical activity (PA) and healthy eating (HE) lifestyle intervention improved both behaviours, limited gestational weight gain (GWG) and was cost-effective. Although GDM risk was unchanged, neonatal adiposity was reduced due to less sedentary time. Neither PA nor HE alone limited GWG or GDM risk. Fasting glucose was higher with HE only intervention, and lower with Vitamin D supplementation. Our combined intervention did not prevent GDM, but was cost-effective, limited GWG and reduced neonatal adiposity.
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http://dx.doi.org/10.1007/s11892-019-1282-7DOI Listing
December 2019

Levels of syndecan-1 and hyaluronan in early- and late-onset preeclampsia.

Pregnancy Hypertens 2019 Oct 3;18:108-111. Epub 2019 Oct 3.

Division of Reproduction, Department of Obstetrics, Gynecology, and Gynecologic Oncology, Poznan University of Medical Sciences, Poznan, Poland.

Objective: The study aimed to assess serum levels of syndecan-1 (SDC-1) and hyaluronan (HA) in patients with early- and late-onset preeclampsia (PE).

Study Design: Blood samples were collected in the third trimester of pregnancy from 20 women with early-onset PE, 20 with late-onset PE, and 20 with normal pregnancy for the assessment of serum levels of SDC-1 and HA as markers of endothelial injury. PE was categorized as early-onset when diagnosed at <34 weeks of gestation and as late-onset when diagnosed at ≥34 weeks of gestation.

Main Outcome Measures: The degree of endothelial injury in different forms of preeclampsia expressed by serum concentrations of SDC-1 and HA.

Results: Concentration of HA was significantly higher and the level of SDC-1 was significantly lower in patients with PE than in the control group. However, the concentrations of both HA and SDC-1 did not differ significantly between the two groups of PE.

Conclusions: Degree of endothelium injury is comparable in patients with early- and late-onset PE.
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http://dx.doi.org/10.1016/j.preghy.2019.08.165DOI Listing
October 2019

Assessment of selected parameters of placental microstructure in patients with intrahepatic cholestasis of pregnancy.

Ginekol Pol 2019 ;90(8):452-457

Division of Reproduction, Department of Obstetrics, Gynaecology and Gynaecologic Oncology, Poznan University of Medical Sciences, Poznan, Poland.

Objectives: Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder during pregnancy. Cholestasisis associated with increased risk of fetal complications: prematurity, perinatal hypoxia and meconium stained amnioticfluid, and sudden intrauterine fetal death. The exact mechanisms associated with cholestasis fetal sequelae are not fullyunderstood. The aim of the study was the histopathological evaluation of placentas from patients with cholestasis andhealthy pregnant women to establish whether cholestasis is accompanied by changes in placental microstructure.

Material And Methods: The effect of cholestasis on placental microstructure was investigated using placental tissue frompatients with cholestatsis treated with ursodeoxycholic acid (UDCA) and from uncomplicated pregnancies. Five placentalhistopathological features were analyzed: number of syncytial knots, number of capillaries per villous, structure of stroma,presence of Hofbauer cells, and villitis of unknown etiology.

Results: There were no statistically significant differences in any of the studied parameters between cholestasis-affectedand healthy control groups.

Conclusions: There are no diffrences in placental microstructure in cholestasis patients treated with UDCA and in patientswith uncomplicated pregnancy.
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http://dx.doi.org/10.5603/GP.2019.0077DOI Listing
April 2020

Maternal factors, ultrasound and placental function parameters in early pregnancy as predictors of birth weight in low-risk populations and among patients with pre-gestational diabetes.

Ginekol Pol 2019 ;90(7):388-395

Prenatal Diagnostic Center, Gynecology and Obstetrics Hospital, Poznan University of Medical Sciences, Poznan, Poland.

Objectives: The aim of our work was to assess the usefulness of maternal factors, ultrasound and placental function parameters during early pregnancy as predictors of birth weight in populations of healthy pregnant women and women suffering from pregestational diabetes.

Material And Methods: A study group comprised 97 healthy women and 160 women with pregestational diabetes (PGDM, type 1), all in singleton pregnancy. Ultrasound examination was performed between weeks 11 and 14, and in weeks 20 and 30 of gestation, based on recommendations of the Polish Society of Gynecologists and Obstetricians, Ultrasonography Division. We also checked uterine artery blood flow parameters. During the first trimester consultation, all patients were surveyed and the following data were collected: age, BMI, reproductive history, comorbidities and smoking. We also collected blood samples and assessed PlGF, PAPP-A, and BhCG levels.

Results: Our study showed that newborn birth weight negatively correlated with mother's age, her diastolic blood pressure, PI of her uterine arteries and BhCG protein levels. Moreover, birth weight directly correlated with PlGF and PAPPA-A protein levels, and maternal early-pregnancy BMI.

Conclusions: LGA diagnosis in the first trimester of pregnancy allows for selection and modification of some risk factors and closer monitoring of endangered fetuses throughout the pregnancy, with emphasis on the perinatal period. Parameters with confirmed usefulness in the prediction of birth weight in the first trimester included: maternal age, BMI, blood pressure, PAPP-A, BhCG and PlGF levels, fetal CRL and uterine artery PI.
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http://dx.doi.org/10.5603/GP.2019.0067DOI Listing
March 2020

Nutritional Lifestyle Intervention in Obese Pregnant Women, Including Lower Carbohydrate Intake, Is Associated With Increased Maternal Free Fatty Acids, 3-β-Hydroxybutyrate, and Fasting Glucose Concentrations: A Secondary Factorial Analysis of the European Multicenter, Randomized Controlled DALI Lifestyle Intervention Trial.

Diabetes Care 2019 08 10;42(8):1380-1389. Epub 2019 Jun 10.

Gender Medicine Unit, Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria

Objective: In our randomized controlled trial, we investigated the impact of healthy eating (HE) aiming for restricted gestational weight gain (GWG) and physical activity (PA) interventions on maternal and neonatal lipid metabolism.

Research Design And Methods: Obese pregnant women ( = 436) were included before 20 weeks' gestation and underwent glucose testing (oral glucose tolerance test) and lipid profiling at baseline and 24-28 and 35-37 gestational weeks after an at least 10-h overnight fast. This secondary analysis had a factorial design with comparison of HE ( = 221) versus no HE ( = 215) and PA ( = 218) versus no PA ( = 218). Maternal changes in triglycerides (TG), LDL cholesterol, HDL cholesterol, free fatty acids (FFAs), and leptin from baseline to end of pregnancy and neonatal outcomes were analyzed using general linear models with adjustment for relevant parameters.

Results: At 24-28 weeks' gestation, FFAs (mean ± SD, 0.60 ± 0.19 vs. 0.55 ± 0.17 mmol/L, < 0.01) were increased after adjustment for FFA at baseline, maternal age, BMI at time of examination, gestational week, insulin resistance, self-reported food intake, self-reported physical activity, and maternal smoking, and GWG was lower (3.3 ± 2.6 vs. 4.3 ± 2.8 kg, < 0.001, adjusted mean differences -1.0 [95% CI -1.5; -0.5]) in HE versus no HE. Fasting glucose levels (4.7 ± 0.4 vs. 4.6 ± 0.4 mmol/L, < 0.05) and 3-β-hydroxybutyrate (3BHB) (0.082 ± 0.065 vs. 0.068 ± 0.067 mmol/L, < 0.05) were higher in HE. Significant negative associations between carbohydrate intake and FFA, 3BHB, and fasting glucose at 24-28 weeks' gestation were observed. No differences between groups were found in oral glucose tolerance test or leptin or TG levels at any time. Furthermore, in PA versus no PA, no similar changes were found. In cord blood, elevated FFA levels were found in HE after full adjustment (0.34 ± 0.22 vs. 0.29 ± 0.16 mmol/L, = 0.01).

Conclusions: HE intervention was associated with reduced GWG, higher FFAs, higher 3BHB, and higher fasting glucose at 24-28 weeks of gestation, suggesting induction of lipolysis. Increased FFA was negatively associated with carbohydrate intake and was also observed in cord blood. These findings support the hypothesis that maternal antenatal dietary restriction including carbohydrates is associated with increased FFA mobilization.
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http://dx.doi.org/10.2337/dc19-0418DOI Listing
August 2019

The DALI vitamin D randomized controlled trial for gestational diabetes mellitus prevention: No major benefit shown besides vitamin D sufficiency.

Clin Nutr 2020 03 11;39(3):976-984. Epub 2019 Apr 11.

Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Public and Occupational Health, Amsterdam Public Health Research Institute, Amsterdam, Netherlands; Institute of Sport Science, University of Graz, Graz, Austria.

Background & Aims: As vitamin D deficiency is associated with an increased risk of gestational diabetes mellitus (GDM), we aimed to test vitamin D supplementation as a strategy to reduce GDM risk (evaluated after fasting plasma glucose (FPG), insulin resistance and weight gain) in pregnant overweight/obese women.

Methods: The DALI vitamin D multicenter study enrolled women with prepregnancy body mass index (BMI) ≥ 29 kg/m, ≤19 + 6 weeks of gestation and without GDM. Participants were randomized to receive 1600 IU/day vitamin D3 or placebo (each with or without lifestyle intervention) on top of (multi)vitamins supplements. Women were assessed for vitamin D status (sufficiency defined as serum 25-hydroxyvitamin D (25(OH)D) ≥ 50 nmol/l), FPG, insulin resistance and weight at baseline, 24-28 and 35-37 weeks. Linear or logistic regression analyses were performed to assess intervention effects.

Results: Average baseline serum 25(OH)D was ≥50 nmol/l across all study sites. In the vitamin D intervention arm (n = 79), 97% of participants achieved target serum vitamin 25(OH)D (≥50 nmol/l) at 24-28 weeks and 98% at 35-37 weeks vs 74% and 78% respectively in the placebo arm (n = 75, p < 0.001). A small but significantly lower FPG (-0.14 mmol/l; CI95 -0.28, -0.00) was observed at 35-37 weeks with the vitamin D intervention without any additional difference in metabolic status, perinatal outcomes or adverse event rates.

Conclusion: In the DALI vitamin D trial, supplementation with 1600 IU vitamin D3/day achieved vitamin D sufficiency in virtually all pregnant women and a small effect in FPG at 35-37 weeks. The potential of vitamin D supplementation for GDM prevention in vitamin D sufficient populations appears to be limited.

Trial Registration Number: ISRCTN70595832.
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http://dx.doi.org/10.1016/j.clnu.2019.04.006DOI Listing
March 2020

Maternal risk factors for neonatal acidosis in women with type 1 diabetes.

Pol Arch Intern Med 2019 05 25;129(5):316-320. Epub 2019 Apr 25.

Division of Reproduction, Poznan University of Medical Sciences, Poznań, Poland

INTRODUCTION Type 1 diabetes in the mother is associated with high risk of adverse neonatal outcomes. OBJECTIVES The aim of this study was to identify maternal factors associated with low arterial pH values (pH <7.10) in infants of mothers with type 1 diabetes. PATIENTS AND METHODS Data from 789 women were included in the analysis. Based on pH values in the umbilical arteries of infants, women were divided into 2 groups: those with normal pH, defined as pH of 7.1 or higher, and those with low pH, defined as pH lower than 7.1. A logistic regression analysis was used to identify the determinants of low pH in the umbilical artery, with data presented as odds ratios and 95% CIs. RESULTS Low umbilical artery pH was observed in 72 infants (9.1%). There was an association between maternal glycated hemoglobin A1c (HbA1c) levels measured before delivery and low umbilical artery pH (odds ratio [OR] 1.40; 95% CI, 1.11-1.78; P = 0.01). A similar association was found for HbA1c levels measured between 20 and 24 weeks' gestation (OR 1.29; 95% CI, 1.03-1.63; P = 0.03). There was no association between the levels of HbA1c in the first trimester or lack of preconception care and low umbilical artery pH. In logistic regression, urgent cesarean section was associated with low umbilical artery pH (OR, 1.64; 95% CI, 1.11-2.44; P = 0.01), and this association was independent of HbA1c levels measured before delivery. CONCLUSIONS Lack of sufficient glycemic control in pregnancy is the strongest predictor of neonatal acidosis in women with type 1 diabetes.
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http://dx.doi.org/10.20452/pamw.14809DOI Listing
May 2019

Continuous subcutaneous insulin infusion reduces neonatal risk in pregnant women with type 1 diabetes mellitus.

Ginekol Pol 2019 ;90(3):154-160

Department of Reproduction, Poznan University of Medical Sciences, Poznan, Poland.

Objectives: An attempt was made to demonstrate the superiority of the treatment model using continuous subcutaneous insulin infusion (CSII) over multiple daily injections (MDI) of insulin in achieving a successful pregnancy outcome and good newborn's condition in patients with type 1 diabetes.

Material And Methods: The study included 297 infants born to type 1 diabetic patients; 175 patients were treated with MDI and 122 with CSII. Maternal metabolic control during pregnancy, gestational weight gain, insulin requirements, pregnancy outcome and neonatal status were compared between MDI and CSII arm. The composite adverse neonatal outcome was diagnosed if at least one of the following was found: abnormal birth weight (LGA or SGA), congenital malformation, miscarriage, intrauterine fetal death, emergency CS due to fetal risk, iatrogenic prematurity, RDS, hypoglycemia, hyperbilirubinemia, and the postpartum pH in the umbilical artery ≤ 7.1.

Results: The studied groups did not differ regarding gestational week at delivery, a proportion of births at full term, preterm births, miscarriages, or late pregnancy losses (intrauterine fetal death > 22 weeks). Newborns of mothers treated with CSII showed lower incidence of neonatal complications (composite adverse neonatal outcome) compared to those of mothers treated with MDI (60% vs 74%, respectively; p = 0.01). We did not find any association between the mode of treatment and composite adverse maternal outcome.

Conclusions: The use of CSII in the treatment of pregnant women with type 1 diabetes was associated with reduced number of neonatal complications presented as neonatal composite outcome but had no influence on maternal outcome.
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http://dx.doi.org/10.5603/GP.2019.0028DOI Listing
February 2020