The MTNR1B rs10830963 Variant in Interaction with Pre-Pregnancy BMI is a Pharmacogenetic Marker for the Initiation of Antenatal Insulin Therapy in Gestational Diabetes Mellitus

The rs10830963 variant of the Melatonin Receptor 1B (MTNR1B) gene is associated with the development of gestational diabetes mellitus (GDM). We hypothesized that carrying the rs10830963/G risk allele had effect on antenatal insulin therapy (AIT) initiation in GDM in a body mass index (BMI)-dependent manner. Design: In this post hoc analysis the MTNR1B rs10830963 genotype and the clinical data of 211 Caucasian GDM patients were assessed. As a first step, a pre-pregnancy BMI threshold was determined where the effect of MTNR1B rs10830963/G allele carrying on AIT initiation was the most significant using logistic regression. Maternal age adjusted real-life odds ratios (OR) values were calculated. The chi-square test was also used to calculate the p value and 10.000 bootstrap simulations were performed in each case to re-assess the statistical power and the OR. Carrying the MTNR1B rs10830963/G allele increased the odds of AIT initiation (OR = 5.2, p = 0.02 [χ2 test], statistical power = 0.53) in GDM patients with pre-pregnancy BMI ≥ 29 kg/m2. The statistical power reached 0.77, when the pre-pregnancy BMI cutoff of 27 kg/m2 was used and the genetic effect on AIT initiation was still significant, but only using the logistic regression model. Carrying the MTNR1B rs10830963/G risk allele—in interaction with pre-pregnancy BMI—is likely be considered as a candidate pharmacogenetic marker of antenatal insulin therapy initiation and should be further assessed in precision medicine trials in GDM

Vitamin D3 Supplementation in Overweight/Obese Pregnant Women:No Effects on the Maternal or Fetal Lipid Profile and Body Fat Distribution—A Secondary Analysis of the Multicentric, Randomized, Controlled Vitamin D and Lifestyle for Gestational Diabetes Prevention Trial (DALI)

Vitamin D deficiency is a common finding in overweight/obese pregnant women and is associated with increased risk for adverse pregnancy outcome. Both maternal vitamin D deficiency and maternal obesity contribute to metabolic derangements in pregnancy. We aimed to assess the effects of vitamin D3 supplementation in pregnancy versus placebo on maternal and fetal lipids. Main inclusion criteria were: women &lt;20 weeks’ gestation, BMI ≥ 29 kg/m2. Eligible women (n = 154) were randomized to receive vitamin D3 (1600 IU/day) or placebo. Assessments were performed &lt;20, 24–28 and 35–37 weeks and at birth. Linear regression models were used to assess effects of vitamin D on maternal and cord blood lipids. In the vitamin D group significantly higher total 25-OHD and 25-OHD3 levels were found in maternal and cord blood compared with placebo. Adjusted regression models did not reveal any differences in triglycerides, LDL-C, HDL-C, free fatty acids, ketone bodies or leptin between groups. Neonatal sum of skinfolds was comparable between the two groups, but correlated positively with cord blood 25-OH-D3 (r = 0.34, p = 0.012). Vitamin D supplementation in pregnancy increases maternal and cord blood vitamin D significantly resulting in high rates of vitamin D sufficiency. Maternal and cord blood lipid parameters were unaffected by Vitamin D3 supplementation.</p

Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development

CONTEXT: Genetic variation in human maternal DNA contributes to the susceptibility for development of gestational diabetes mellitus (GDM). OBJECTIVE: We assessed 77 maternal single nucleotide gene polymorphisms (SNPs) for associations with GDM or plasma glucose levels at OGTT in pregnancy. METHODS: 960 pregnant women (after dropouts 820: case/control: m99'WHO: 303/517, IADPSG: 287/533) were enrolled in two countries into this case-control study. After genomic DNA isolation the 820 samples were collected in a GDM biobank and assessed using KASP (LGC Genomics) genotyping assay. Logistic regression risk models were used to calculate ORs according to IADPSG/m'99WHO criteria based on standard OGTT values. RESULTS: The most important risk alleles associated with GDM were rs10830963/G of MTNR1B (OR = 1.84/1.64 [IADPSG/m'99WHO], p = 0.0007/0.006), rs7754840/C (OR = 1.51/NS, p = 0.016) of CDKAL1 and rs1799884/T (OR = 1.4/1.56, p = 0.04/0.006) of GCK. The rs13266634/T (SLC30A8, OR = 0.74/0.71, p = 0.05/0.02) and rs7578326/G (LOC646736/IRS1, OR = 0.62/0.60, p = 0.001/0.006) variants were associated with lower risk to develop GDM. Carrying a minor allele of rs10830963 (MTNR1B); rs7903146 (TCF7L2); rs1799884 (GCK) SNPs were associated with increased plasma glucose levels at routine OGTT. CONCLUSIONS: We confirmed the robust association of MTNR1B rs10830963/G variant with GDM binary and glycemic traits in this Caucasian case-control study. As novel associations we report the minor, G allele of the rs7578326 SNP in the LOC646736/IRS1 region as a significant and the rs13266634/T SNP (SLC30A8) as a suggestive protective variant against GDM development. Genetic susceptibility appears to be more preponderant in individuals who meet both the modified 99'WHO and the IADPSG GDM diagnostic criteria

Written Briefing and Oral Counseling Increase the Willingness to Receive the SARS-CoV-2 Vaccination among Women in Puerperium: A Qualitative Prospective Cohort Study

(1) Background: Vaccination rates for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) are low in Austria. International obstetric societies recommend the SARS-CoV-2 mRNA vaccination for women in puerperium. (2) Methods: A prospective two-stage cohort study was conducted at the Medical University of Vienna between October 2022 and December 2022. Firstly, women in puerperium were assigned to the evaluation group (step 1), and secondly, another cohort of unvaccinated women were randomly assigned to study group A (written briefing) or B (written and oral briefing) (step 2). We evaluated the vaccination status among women in the evaluation group and the willingness to receive the vaccination in all three cohorts. (3) Results: We included 217 women in puerperium (evaluation: n = 69, A: n = 68; B: n = 80). In the evaluation group, 66.7% (n = 46/69) of the women were unvaccinated. A total of 45.7% (21/46) of the unvaccinated women categorically declined the SARS-CoV-2 vaccination. A total of 26.5% (n = 18/68) of women in study group A, and 43.8% (n = 35/80) of women in study group B expressed their willingness to receive the vaccination (p = 0.029). There were no differences in willingness to receive the vaccination between different age strata of women in study groups A and B. (D) Conclusion: Our qualitative data demonstrate a benefit from oral counseling in addition to written briefing in order to increase the willingness to receive the vaccination among women in puerperium

Behcet's disease of the uterine cervic - A case report M. Behcet der Cervix uteri - Ein Fallbericht

Behcet's disease is a chronic disorder of unclear pathogenesis defined by multiple genital and oral ulcers, as well as ophthalmic changes. The patient described in this case report presented clinically with recurrent genital discharge, recurrent mild genital pain and a cervical ulcer. The diagnosis of Behcet's disease was established by the presence of cervical ulceration, two minor aphthous lesions in the vestibulum oris and a positive pathergy test. Although rare, Behcet's disease should be considered in the differential diagnosis of genital ulceration of unknown etiology

Gestationsdiabetes (GDM) (Update 2019)

Gestationsdiabetes (GDM) wird als Glukosetoleranzstörung definiert, die erstmals in der Schwangerschaft entdeckt wird. GDM ist mit einer erhöhten fetomaternalen Morbidität sowie Langzeitkomplikationen bei Mutter und Kind assoziiert. Frauen, die die Kriterien eines manifesten Diabetes bereits in der Frühschwangerschaft erfüllen (Nüchternplasmaglukose >126 mg/dl, Spontanglukosemessung über 200 mg/dl oder HbA1c > 6,5 % vor der 20. Schwangerschaftswoche), sollen als Schwangere mit manifestem Diabetes klassifiziert und ebenso behandelt werden. Ein Screening auf unerkannten Typ-2-Diabetes bei der ersten pränatalen Kontrolle wird besonders bei Frauen mit hohem Risiko (Anamnese eines GDM oder Prädiabetes; Fehlbildungen, Totgeburt, wiederholte Aborte oder Geburtsgewicht über 4500 g in früheren Schwangerschaften; Adipositas, metabolisches Syndrom, Alter über 35 Jahre, bei Gefäßerkrankungen, Auftreten von Diabetessymptomen wie Glukosurie, ethnische Zugehörigkeit zu Gruppen mit hohem Risiko [arabisch, S und SO-Asien, Lateinamerika]) empfohlen (Evidenzklasse B). GDM wird durch einen oralen Glukosetoleranztest (OGTT) oder durch Nüchternplasmaglukosekonzentrationen über 92 mg/dl diagnostiziert. Bei hohem Risiko kann ein OGTT (120 min; 75 g Glukose) bereits im ersten Trimenon sinnvoll sein, ist aber in jedem Fall bei allen Schwangeren mit bis dahin unauffälligen Glukosewerten zwischen der 24. und 28. Schwangerschaftswoche vorgeschrieben (Evidenzklasse B). Auf Basis der „Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study“ und nach den aktuellen WHO-Empfehlungen liegt ein GDM vor, wenn der Nüchternplasmaglukosewert 92 mg/dl, der 1Stunden-Wert 180 mg/dl oder der 2Stunden-Wert 153 mg/dl überschreiten (OGTT; Internationale Konsensuskriterien). Ein einziger erhöhter Wert ist für die Diagnose ausreichend und bedarf bereits einer strikten Stoffwechselkontrolle. Nach bariatrischer Operation wird aufgrund der Gefahr einer postprandialen Hypoglykämie die Durchführung eines OGTT nicht empfohlen. Alle Frauen mit GDM erhalten eine Ernährungsberatung und müssen ihre Blutzuckerwerte regelmäßig kontrollieren. Ebenso sollte, falls nicht kontraindiziert, die körperliche Aktivität erhöht werden. Falls die Blutzuckerspiegel nicht im Therapiebereich liegen (nüchtern <95 mg/dl und 1 h nach den Mahlzeiten <140 mg/dl) soll als erste Wahl eine Insulintherapie initiiert werden. Neben der mütterlichen Stoffwechselüberwachung ist auch ein fetales Monitoring notwendig, um die mütterliche und fetale/neonatale Morbidität und die perinatale Mortalität möglichst gering zu halten. Alle Frauen mit GDM müssen 4 bis 12 Wochen nach der Entbindung neuerlich einen OGTT (75 g; WHO-Kriterien) durchführen lassen, um ihre Glukosetoleranz neu zu klassifizieren. Bei Normalbefund soll der OGTT alle 2 Jahre wiederholt werden (Evidenzklasse B). Alle Frauen müssen über ihr (7-fach erhöhtes relatives) Risiko informiert werden, im weiteren Verlauf einen Typ-2-Diabetes zu entwickeln, sowie über mögliche Präventionsmaßnahmen. Dazu gehören Gewichtsreduktion bei Übergewicht, gesunde Ernährung und ausreichend körperliche Aktivität. Auch die Kinder sollen hinsichtlich einer unauffälligen Entwicklung regelmäßig nachuntersucht werden, und die ganze Familie soll über Lebensstilmaßnahmen zur Aufrechterhaltung/Verbesserung der Gesundheit informiert werden. Die regelmäßige Durchführung von geburtshilflichen Kontrollen sowie Ultraschalluntersuchungen wird empfohlen. Im Rahmen der neonatalen Untersuchungen müssen bei Neugeborenen von GDM-Müttern Blutzuckerkontrollen erfolgen und bei Erfordernis geeignete Maßnahmen eingeleitet werden.Gestational diabetes mellitus (GDM) is defined as a glucose tolerance disorder with onset during pregnancy and is associated with increased feto-maternal morbidity as well as long-term complications in mother and child. Women who fulfil the criteria of a manifest diabetes in early pregnancy (fasting plasma glucose >126 mg/dl, spontaneous glucose level >200 mg/dl or HbA1c > 6.5% before 20 weeks of gestation) should be classified as having manifest diabetes in pregnancy and treated as such. Screening for undiagnosed type 2 diabetes at the first prenatal visit (evidence level B) is particularly recommended in women at increased risk (history of GDM or prediabetes, malformation, stillbirth, successive abortions or birth weight >4500 g in previous pregnancies, obesity, metabolic syndrome, age >35 years, vascular disease, clinical symptoms of diabetes, e. g. glucosuria, or ethnic groups with increased risk for GDM/T2DM, e.g. Arabian countries, south and southeast Asia and Latin America). A GDM is diagnosed by an oral glucose tolerance test (OGTT) or a fasting glucose concentration 92 mg/dl. Performance of the OGTT (120 min, 75 g glucose) may already be indicated in the first trimester in high risk women but is mandatory between 2428 gestational weeks in all pregnant women with previous non-pathological glucose metabolism (evidence level B). Based on the results of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study and following the recent WHO recommendations, GDM is present if the fasting plasma glucose level exceeds 92 mg/dl, the 1 h level exceeds 180 mg/dl or the 2 h level exceeds 153 mg/dl after glucose loading (OGTT international consensus criteria). A single increased value is sufficient for the diagnosis and a strict metabolic control is mandatory. After bariatric surgery an OGTT is not recommended due to the risk of postprandial hypoglycemia. All women with GDM should receive nutritional counselling, be instructed in self-monitoring of blood glucose and to increase physical activity to moderate intensity levels, if not contraindicated. If blood glucose levels cannot be maintained in the therapeutic range (fasting <95 mg/dl and 1 h postprandial <140 mg/dl) insulin therapy should be initiated as first choice. Maternal and fetal monitoring is required in order to minimize maternal and fetal/neonatal morbidity and perinatal mortality. After delivery all women with GDM have to be re-evaluated by a 75 g OGTT (WHO criteria) 412 weeks postpartum to reclassify the glucose tolerance and every 2 years in cases of normal glucose tolerance (evidence level B). All women have to be informed about their (sevenfold increased relative) risk of developing type 2 diabetes (T2DM) at follow-up and possible preventive measures, in particular weight management, healthy diet and maintenance/increase of physical activity. Monitoring of the development of children and recommendations for a healthy lifestyle are necessary for the whole family. Regular obstetric examinations including ultrasound examinations are recommended. Within the framework of neonatal care, neonates of GDM mothers should undergo blood glucose measurements and if necessary appropriate measures should be initiated.(VLID)365882

BMC Pregnancy and Childbirth / A retrospective study on perineal lacerations in vaginal delivery and the individual performance of experienced mifwives

Background Medical staffs influence on patient outcomes has become a subject of interest. We evaluated experienced midwives and compared their performance concerning perineal lacerations (PL). Methods In a retrospective cohort study, 1937 women with singleton pregnancies who had delivered spontaneously with a cephalic presentation by experienced midwives in the Medical University of Vienna from January 2009 to April 2014 were included. As predictive parameters, we included basic patient-, pregnancy- and delivery-related characteristics including the individual midwife who delivered the child. The incidence of PL was the main outcome measure. Results Overall PL and severe PL were found in 508/1937 (26.2 %) and 19/1937 women (1.0 %), respectively. In a multivariate analysis for PL of any degree, maternal age (ß=0.1700.080), gestational age at delivery (ß=0.1900.320), and birth weight (ß=0.0020.000) significantly increased the risk, whereas multiparity (ß=0.3790.141) and mediolateral episiotomy (ß=1.5140.284) decreased it (p<0.05). In addition, the individual midwife who delivered the child was a significant influencing factor, with ß-values ranging from 0.028 to 0.899 compared to the reference midwife. For severe PL, the midwife was not of significant influence. Conclusions The individual midwife is an independent factor that influences the risk for overall PL, not for severe PL. Other risk factors include maternal age, gestational age at delivery, birth weight, parity and episiotomy.(VLID)486419

Influence of delayed on established prognostic factors in endometrial cancer

To evaluate the influence of delayed diagnosis on prognostic factors in endometrial cancer, we conducted a retrospective chart analysis based on the data of 116 postmenopausal patients with FIGO stage I-IV endometrial carcinoma. The interval from the first episode of postmenopausal vaginal bleeding to definitive, histological diagnosis (bleeding interval) was compared with tumor stage and various histomorphologic features in endometrial cancer. The mean bleeding interval was 12.7 ± 17.8 weeks in 74 patients with FIGO stage IA, IB endometrial carcinoma and 35.2 ± 69.3 weeks in 42 patients with stage IC-IV disease (t-test, p: 0.011). FIGO stage IA, IB disease was diagnosed in 23/26 (88%) patients with a bleeding inten