Identifying microbiome-based changes and biomarkers prior to disease development in mother and child, with a focus on gestational diabetes mellitus: protocol for the DANish Maternal and Offspring Microbiome (DANMOM) cohort study.

INTRODUCTION: The human gut microbiota is associated with gestational diabetes mellitus (GDM), which imposes a risk of developing long-term health problems for mother and child. Most studies on GDM and microbiota have been cross-sectional, which makes it difficult to make any conclusions on causality. Furthermore, it is important to assess if a dysbiotic microbiota is passed from the mother to the child, and then being at risk of developing metabolic health problems later in life. The DANish Maternal and Offspring Microbiome study aims to identify gut microbiota-related factors involved in metabolic dysfunction in women with GDM and their offspring. Importantly, the study design allows for early detection of biological changes associated with later development of metabolic disease. This could provide us with unique tools to support early diagnosis or implement preventative measures. METHODS AND ANALYSIS: Pregnant women are included in the study after the 11-14 weeks' prenatal ultrasound scan and followed throughout pregnancy with enrolment of the offspring at birth. 202 women and 112 children have been included from North Denmark Regional Hospital and Aalborg University Hospital in Denmark. Mother and child are followed until the children reach the age of 5 years. From the mother, we collect faeces, urine, blood, saliva, vaginal fluid and breast milk samples, in addition to faeces and a blood sample from the child. Microbiota composition in biological samples will be analysed using 16S rRNA gene sequencing and compared with demographic and clinical data from medical charts, registers and questionnaires. Sample and data collection will continue until July 2028. ETHICS AND DISSEMINATION: The study protocol has been approved by the North Denmark Region Committee on Health Research Ethics (N20190007). Written informed consent is obtained from all participants prior to study participation. Study results will be published in international peer-reviewed journals and presented at international conferences. The results will also be presented to the funders of the study and study participants.

Effect of short-term changes in salt intake on plasma cytokines in women with healthy and hypertensive pregnancies.

BACKGROUND: Salt (NaCl) promotes T-lymphocyte conversion to pro-inflammatory Th-17 cells in vitro. Interleukin (IL)-17A aggravates hypertension in preeclampsia (PE) models. OBJECTIVES: It was hypothesized that 1) women with PE exhibit increased plasma IL-17A and related cytokines and 2) high dietary salt intake elevates circulating IL-17A in patients with PE compared to women with healthy pregnancy (HP) and non-pregnant (NonP) women. MAIN OUTCOME MEASURES: Plasma concentration of cytokines IL-17A, IFN-γ, IL-10, TNF, IL-6, and IL-1ß in samples from NonP women (n = 13), HP (n = 15), and women with PE (n = 7). STUDY DESIGN: Biobanked samples from a randomized, double-blind, cross-over placebo-controlled dietary intervention study. Participants received a low sodium diet (50-60 mmol NaCl/24 h) for 10 days and were randomly assigned to ingest placebo tablets (low salt intake) or salt tablets (172 mmol NaCl/24 h, high salt intake) for 5 + 5 days. Plasma samples were drawn at baseline and after each diet. RESULTS: While a high salt diet suppressed renin, angiotensin II, and aldosterone levels, it did not affect blood pressure or plasma cytokine concentrations in any group compared to low salt intake. Plasma TNF was significantly higher in PE than in HP and NonP at baseline and after a low salt diet. Plasma IL-6 was significantly higher in PE compared to HP at baseline and NonP at low salt. CONCLUSION: Interleukin-17A and related T-cell and macrophage-cytokines are not sensitive to salt-intake in PE. Preeclampsia is associated with elevated levels of TNF and IL-6 macrophage-derived cytokines. Salt-sensitive changes in systemic IL-17A are less likely to explain hypertension in PE.

Clinical and Metabolic Characterization of Women With Gestational Diabetes Mellitus Within the First Year Postpartum.

Context: Women with gestational diabetes mellitus (GDM) have an increased risk of long-term complications, including impaired glucose metabolism, type 2 diabetes (T2DM), cardiovascular disease, and obesity. In current clinical practice, a 1 size fits all approach to GDM is applied, although heterogeneity among women with GDM has been recognized. Objective: To give the most adequate preventive care and postpartum (PP) guidance, we aimed to make a metabolic characterization and identify subgroups of women with previous GDM within the first year PP. Methods: In this prospective cohort study, we collected data in gestational week 34-38, at 3 months, and 1 year PP on women with GDM who participated in a PP follow-up program in Central Region Denmark from April 2019 to December 2022. Results: In total, 1270 women were included in the program in late pregnancy. Of the 768 women participating in either the oral glucose tolerance test 3 months PP (n = 545) or the 1-year follow-up (n = 493) or both (n = 261), 608 (79.2%) were normoglycemic, 137 (17.8%) had prediabetes, 20 (2.6%) had T2DM, and 3 (.4%) had developed T1DM. More than 40% of the women gained weight in the first year PP compared with their pregestational weight. Conclusion: Our study shows that 20.8% of women with GDM who volunteered to participate in a clinical follow-up program developed prediabetes or diabetes (T1DM and T2DM) within the first year PP. The GDM diagnosis encompasses a heterogenetic group of women and a deeper characterization may provide an opportunity for a more personalized risk assessment to prevent the progression to T2DM.

Offspring preterm birth and birth size are related to long-term risk of maternal diabetes.

The aim of the study is to investigate the association between gestational age, birth size, and the long-term risk of maternal diabetes. We conducted a nation-wide prospective follow-up study of the cohort of all Danish women with a singleton delivery in 1982/1983 (index delivery) and no history of diabetes (n = 100,669). Registries were used to extract information on patients with a hospital or outpatient diagnosis of diabetes, subsequent deliveries, and death/emigration in the period from the index delivery until the end of 2006. The association between the maternal risk of diabetes and the index gestational age and index offspring birth size (birth weight adjusted for gestational age) was investigated by using Cox proportional hazards regression models stratified according to young (≤33 years) and old age (>33 years). During a median follow-up period of 24 years, 2,021 women (2.0 %) were diagnosed as having diabetes. The risk of maternal diabetes was positively associated with increasing index birth size and negatively associated with increasing duration of index gestation in both age strata. Among young women, the highest hazard ratios were found for the exposure category of large index offspring birth size (adjusted HR 9.0, 95 % CI 6.17-13.12) and a preterm delivery at 32-37 weeks (adjusted HR 2.22, 95 % CI 1.46-3.40). Offspring preterm birth and large size for gestational age at birth are associated with increased risk of maternal diabetes.

Breastfeeding and insulin requirements in women with Type 1 diabetes mellitus in the first year postpartum.

AIMS: To explore whether breastfeeding affects postpartum insulin requirements, HbA1c levels, and pregnancy weight retention in women with Type 1 Diabetes Mellitus (T1DM). METHODS: This prospective study included 66 women with T1DM. The women were divided into two groups based on whether they were breastfeeding (BF) at 6 months postpartum (BFyes, n = 32) or not (BFno, n = 34). Mean daily insulin requirement (MDIR), HbA1c levels, and pregnancy weight retention at 5 time-points from discharge to 12 months postpartum were compared. RESULTS: MDIR increased by 35% from 35.7 IU at discharge to 48.1 IU at 12 months postpartum (p < 0.001). MDIR in BFyes and BFno were comparable, however in BFyes, MDIR were continuously lower compared to BFno. Postpartum HbA1c increased rapidly from 6.8% at 1 month to 7.4% at 3 months postpartum and settled at 7.5% at 12 months postpartum. The increase in HbA1c during the first 3 months postpartum was most pronounced in BFno (p < 0.001). Although neither were statistically significant, from 3 months postpartum HbA1c levels were highest in the BFno and BFno had a higher pregnancy weight retention compared to BFyes (p = 0.31). CONCLUSION: In women with T1DM, breastfeeding did not significantly affect postpartum insulin requirements, HbA1c levels or pregnancy weight retention in the first year after delivery.

Transplacental Transport of Artificial Sweeteners.

The prevalence of obesity is increasing, and the origins of obesity and metabolic dysfunction may be traced back to fetal life. Currently, overweight pregnant women are advised to substitute sugar-sweetened beverages with diet drinks containing artificial sweeteners. Recent evidence suggests that the consumption of artificial sweeteners during pregnancy increases the risk of obesity in the child, but the mechanism is unknown. We hypothesized the transportation of artificial sweeteners across the placenta into the fetal circulation and the amniotic fluid. We included 19 pregnant women who were given an oral dose of acesulfame, cyclamate, saccharin, and sucralose immediately before a planned caesarean section. Nine women were included as controls, and they refrained from an intake of artificial sweeteners. The maternal and fetal blood and amniotic fluid were collected during the caesarean section, and concentrations of artificial sweeteners were measured using mass spectrometry. We found a linear relationship between the fetal plasma concentrations of artificial sweeteners and the maternal plasma concentrations, with adjusted coefficients of 0.49 (95% CI: 0.28-0.70) for acesulfame, 0.72 (95% CI: 0.48-0.95) for cyclamate, 0.51 (95% CI: 0.38-0.67) for saccharin, and 0.44 (95% CI: 0.33-0.55) for sucralose. We found no linear relationship between amniotic fluid and fetal plasma concentrations, but there were positive ratios for all four sweeteners. In conclusion, the four sweeteners investigated all crossed the placenta and were present in the fetal circulation and amniotic fluid.

[Pregnancy after simultaneouspancreasandkidney transplantation].

In this case report, a 41-year-old nullipara obtained pregnancy one and a half year after a simultaneous pancreas and kidney transplantation (SKP). After SKP, the woman had no need for insulin and no hypertension. Her kidney function was stable during pregnancy and no insulin was needed. During the last weeks of pregnancy, increased blood pressure was seen. Biochemically, there were no signs of preeclampsia and no proteinuria. An elective cesarean section was performed in gestational week 37+5 and a healthy boy, 2,710 g. (-1.2 standarddeviation) was born. Pregnancy after SKP is possible and can have a good prognosis.

Extreme insulin resistance during pregnancy: a therapeutic challenge.

SUMMARY: During pregnancy, maternal tissues become increasingly insensitive to insulin in order to liberate nutritional supply to the growing fetus, but occasionally insulin resistance in pregnancy becomes severe and the treatment challenging. We report a rare and clinically difficult case of extreme insulin resistance with daily insulin requirements of 1420 IU/day during pregnancy in an obese 36-year-old woman with type 2 diabetes (T2D) and polycystic ovary syndrome (PCOS). The woman was referred to the outpatient clinic at gestational week 12 + 2 with a hemoglobin A1c (HbA1c) at 59 mmol/mol. Insulin treatment was initiated immediately using Novomix 30, and the doses were progressively increased, peaking at 1420 units/day at week 34 + 4. At week 35 + 0, there was an abrupt fall in insulin requirements, but with no signs of placental insufficiency. At week 36 + 1 a, healthy baby with no hypoglycemia was delivered by cesarean section. Blood samples were taken late in pregnancy to search for causes of extreme insulin resistance and showed high levels of C-peptide, proinsulin, insulin-like growth factor (IGF-1), mannan-binding-lectin (MBL) and leptin. CRP was mildly elevated, but otherwise, levels of inflammatory markers were normal. Insulin antibodies were undetectable, and no mutations in the insulin receptor (INSR) gene were found. The explanation for the severe insulin resistance, in this case, can be ascribed to PCOS, obesity, profound weight gain, hyperleptinemia and inactivity. This is the first case of extreme insulin resistance during pregnancy, with insulin requirements close to 1500 IU/day with a successful outcome, illustrating the importance of a close interdisciplinary collaboration between patient, obstetricians and endocrinologists. LEARNING POINTS: This is the first case of extreme insulin resistance during pregnancy, with insulin requirements of up to 1420 IU/day with a successful outcome without significant fetal macrosomia and hypoglycemia. Obesity, PCOS, T2D and high levels of leptin and IGF-1 are predictors of severe insulin resistance in pregnancy. A close collaboration between patient, obstetricians and endocrinologists is crucial for tailoring the best possible treatment for pregnant women with diabetes, beneficial for both the mother and her child.

The Impact of Lifestyle, Diet and Physical Activity on Epigenetic Changes in the Offspring-A Systematic Review.

AIMS: This systematic review examines the association between maternal lifestyle, diet and physical activity, and epigenetic changes in the offspring. METHODS: A literature search was conducted using multiple science databases: PubMed, Embase and Cochrane Library, on 10 March 2021. RCT and Cohort studies in English or Scandinavian languages were included. Exposure variables included diet, lifestyle, meal patterns or physical activity. Studies using dietary supplements as exposure variables were excluded. Outcome variables included were DNA methylation, microRNA or histone changes in placenta, cord blood or offspring. Two independent authors screened, read and extracted data from the included papers. The Cochrane risk-of-bias tool for randomized trials (RoB2) and The Critical Appraisal Skills Program (CASP) Cohort Study Checklist were used to assess risk of bias in the included studies. A qualitative approach was employed due to heterogeneity of exposures and results of the studies. RESULTS: 16 studies and 3617 participants were included in the final analysis. The exposure variables included physical activity, carbohydrate, low glycemic index diet, added sugar, fat, Mediterranean diet and pro-inflammatory diet. The outcome variables identified were differences in DNA methylation and microRNA. Most studies described epigenetic changes in either placenta or cord blood. Genes reported to be methylated were GR, HSD2, IGF-2, PLAG1, MEG-3, H19 and RXRA. However, not all studies found epigenetic changes strong enough to pass multiple testing, and the study quality varied. CONCLUSION: Despite the variable quality of the included studies, the results in this review suggest that there may be an association between the mother's lifestyle, diet and level of physical activity during pregnancy and epigenetic changes in the offspring.

Glycemic Control in Pregnancies Complicated by Pre-Existing Diabetes Mellitus and Congenital Malformations: A Danish Population-Based Study.

PURPOSE: To study the occurrence of major congenital abnormalities in children of women with type 1 and type 2 diabetes and investigate the association between glycated haemoglobin (HbA1c) and major congenital malformations according to type 1 diabetes and type 2 diabetes separately. PATIENTS AND METHODS: In this register-based study, all singletons born alive from January 1, 2000 to December 31, 2015 in the North Denmark and Central Denmark regions of Denmark and their mothers were included. We used data from Danish health registers and the LABKA database. Logistic regression models were used to compute crude and adjusted prevalence odds ratios (cORs and aORs) with 95% confidence intervals (CIs) for major congenital malformations overall and for subtypes, by type of maternal pre-existing diabetes and HbA1c levels. RESULTS: Among 314,245 infants included, 2020 (0.64%) had mothers with type 1 diabetes and 498 (0.16%) had mothers with type 2 diabetes. We found an aOR of 2.9 (95% CI: 2.5, 3.5) and 1.9 (95% CI: 1.3; 2.8) for major malformations for type 1 and type 2 diabetes, respectively. The highest occurrence was seen for major congenital heart diseases, but we also observed higher occurrence of several other non-cardiac malformations. For both type 1 and type 2 diabetes, the prevalence of major congenital malformations increased with higher levels of maternal HbA1c with no safe threshold level. Mothers with type 1 diabetes had higher risks than those without diabetes irrespective of HbA1c, and women with HbA1c levels ≥9.5% had 8 times the odds of major congenital malformations [aOR 8.7 (95% CI: 5.4; 14.5)]. CONCLUSIONS: The prevalence of major congenital malformations progressively increased with poorer glycemic control during pregnancy, with no obvious safe threshold level, for both type 1 and type 2 diabetes.

Placental superoxide dismutase 3 mediates benefits of maternal exercise on offspring health.

Poor maternal diet increases the risk of obesity and type 2 diabetes in offspring, adding to the ever-increasing prevalence of these diseases. In contrast, we find that maternal exercise improves the metabolic health of offspring, and here, we demonstrate that this occurs through a vitamin D receptor-mediated increase in placental superoxide dismutase 3 (SOD3) expression and secretion. SOD3 activates an AMPK/TET signaling axis in fetal offspring liver, resulting in DNA demethylation at the promoters of glucose metabolic genes, enhancing liver function, and improving glucose tolerance. In humans, SOD3 is upregulated in serum and placenta from physically active pregnant women. The discovery of maternal exercise-induced cross talk between placenta-derived SOD3 and offspring liver provides a central mechanism for improved offspring metabolic health. These findings may lead to novel therapeutic approaches to limit the transmission of metabolic disease to the next generation.

"High prepregnancy HbA1c is challenging to improve and affects insulin requirements, gestational length, and birthweight".

BACKGROUND: The aim of this study was to explore how prepregnancy glycosylated hemoglobin (HbA1c) affects the course of HbA1c and insulin requirements during pregnancy, the gestational length, and birthweight. METHODS: An observational cohort study was conducted consisting of 380 women with type 1 diabetes who gave birth 530 times from 2004 to 2014. The participants were divided into four groups according to prepregnancy HbA1c. RESULTS: HbA1c was significantly different between the groups at all time intervals from week 5 to 10 to week 33 to 36 (P ≤ .01). In group 1, with the lowest prepregnancy HbA1c (<6.5% [48 mmol/mol]), HbA1c stayed at the same level throughout pregnancy. In the other groups (group 2: 6.5% [48 mmol/mol]-7.9% [63 mmol/mol], group 3: 8% [64 mmol/mol]-9.9% [86 mmol/mol], and group 4: > 10% [86 mmol/mol]) a decrease in HbA1c was seen in early pregnancy but stabilized from midpregnancy onward. Group 1 had the lowest daily insulin requirements throughout pregnancy among the four groups (P = .001). The relationship between birthweight and prepregnancy HbA1c was found to be inversely U-shaped. Mean gestational length in group 4 was significantly shorter than in group 1 (P = .001). CONCLUSIONS: In this very large cohort, we found that a poor prepregnancy HbA1c is a predictor for poor glycemic control during pregnancy and that HbA1c decreases until midpregnancy and then plateaus. A very poor prepregnancy HbA1c is associated with shorter gestational length and lower birthweight, which is contrary to the common assumption that poor glycemic control leads to higher birthweight.

Cycling reduces blood glucose excursions after an oral glucose tolerance test in pregnant women: a randomized crossover trial.

The aim of this study was to evaluate the effect of an acute bout of cycling immediately after oral glucose intake on glucose metabolism in pregnant women at risk for gestational diabetes mellitus (GDM). Fifteen pregnant women with BMI ≥ 27 kg/m2 were enrolled in a randomized crossover controlled study and underwent two oral glucose tolerance tests (OGTTs) ingesting 75 g of glucose followed by either 20 min of stationary cycling at moderate intensity (65%-75% maximal heart rate) or rest. Using continuous glucose monitors, glucose was measured up to 48 h after the OGTT. Glucose, insulin, and C-peptide were determined at baseline and after 1 and 2 h. One hour after glucose intake, mean blood glucose was significantly lower after cycling compared with rest (p = 0.002). Similarly, mean glucose peak level was significantly lower after cycling compared with after rest (p = 0.039). Lower levels of insulin and C-peptide were observed after 1 h (p < 0.01). Differences in glucose measurements after 2 h and up to 48 h were not statistically different. We found that 20 min of cycling at moderate intensity after glucose intake reduced blood glucose excursions in pregnant women at risk for GDM. ClinicalTrials.gov Identifier: NCT03644238. Novelty Bullets In pregnant women, we found that cycling after glucose intake resulted in significantly lower glucose levels compared with rest. The exercise intervention studied is feasible for pregnant women and could be readily used to reduce glucose excursions.

Diet and Healthy Lifestyle in the Management of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) among pregnant women increases the risk of both short-term and long-term complications, such as birth complications, babies large for gestational age (LGA), and type 2 diabetes in both mother and offspring. Lifestyle changes are essential in the management of GDM. In this review, we seek to provide an overview of the lifestyle changes which can be recommended in the management of GDM. The diet recommended for women with GDM should contain sufficient macronutrients and micronutrients to support the growth of the foetus and, at the same time, limit postprandial glucose excursions and encourage appropriate maternal gestational weight gain. Blood glucose excursions and hyperglycaemic episodes depend on carbohydrate-intake. Therefore, nutritional counselling should focus on the type, amount, and distribution of carbohydrates in the diet. Further, physical activity has beneficial effects on glucose and insulin levels and it can contribute to a better glycaemic control.

Effect of High Versus Low Carbohydrate Intake in the Morning on Glycemic Variability and Glycemic Control Measured by Continuous Blood Glucose Monitoring in Women with Gestational Diabetes Mellitus-A Randomized Crossover Study.

Carbohydrate is the macronutrient that has the greatest impact on blood glucose response. Limited data are available on how carbohydrate distribution throughout the day affects blood glucose in women with gestational diabetes mellitus (GDM). We aimed to assess how a high-carbohydrate morning-intake (HCM) versus a low-carbohydrate-morning-intake (LCM), affect glycemic variability and glucose control. In this randomized crossover study continuous glucose monitoring (CGM) was performed in 12 women with diet treated GDM (75 g, 2-h OGTT ≥ 8.5 mmol/L), who went through 2 × 3 days of HCM and LCM. A within-subject-analysis showed a significantly higher mean amplitude of glucose excursions (MAGE) (0.7 mmol/L, p = 0.004) and coefficient of variation (CV) (5.1%, p = 0.01) when comparing HCM with LCM, whereas a significantly lower mean glucose (MG) (-0.3 mmol/L, p = 0.002) and fasting blood glucose (FBG) were found (-0.4 mmol/L, p = 0.01) on the HCM diet compared to the LCM diet. In addition, insulin resistance, expressed as Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), decreased significantly during HCM. Results indicate that a carbohydrate distribution of 50% in the morning favors lower blood glucose and improvement in insulin sensitivity in women with GDM, but in contrary gives a higher glycemic variability.

Biodistribution of [11C]-Metformin and mRNA Expression of Placentae Metformin Transporters in the Pregnant Chinchilla.

Background: While metformin is the first-line pharmacological treatment of diabetes mellitus type 2, this drug is not considered safe to use in pregnant women because of its unknown consequences for the fetus. In this study, we aimed to investigate the biodistribution of metformin in the pregnant chinchilla, a species exhibiting placental characteristics comparable with the pregnant woman. Furthermore, we aimed to investigate the expression of metformin transporters in humans and chinchillas, respectively, in order to evaluate the pregnant chinchilla as a novel animal model for the use of metformin in pregnancy. Methods: Three chinchillas in the last part of gestation were injected with [11C]-metformin and scanned by PET/CT for 70 minutes to visualize the distribution. To investigate the difference in expression of placenta transporters between humans and chinchillas, PCR was performed on samples from five chinchilla placentae and seven human placentae. Results: Dynamic PET with [11C]-metformin showed that the metformin distribution in chinchillas was similar to that in nonpregnant humans, with signal from kidneys, liver, bladder, and submandibular glands. Conversely, no radioactive signal was observed from the fetuses, and no metformin was accumulated in the chinchilla fetus when measuring the SUV. PCR of placental mRNA showed that the human placentae expressed OCT3, whereas the chinchilla placentae expressed OCT1. Conclusion: Since metformin did not pass the placenta barrier in the pregnant chinchilla, as it is known to do in humans, we do not suggest the chinchilla as a future animal model of metformin in pregnancies.

Temporal Trends in Gestational Diabetes Prevalence, Treatment, and Outcomes at Aarhus University Hospital, Skejby, between 2004 and 2016.

BACKGROUND: The prevalence of gestational diabetes (GDM) is increasing worldwide. The most important risk of GDM in pregnancy is excessive fetal growth, increasing the risk of complications during delivery as well as long-term complications like obesity and diabetes in both the mother and the offspring. METHOD: All women with GDM who delivered a singleton between 2004 and 2016 were included. The treatment of GDM patients sought to achieve normal blood glucose levels, primarily by diet and exercise. If the glycemic targets were not reached, insulin therapy was initiated. Birth weight and birth weight Z-score was calculated corrected for gender and gestational age at delivery. RESULTS: The study included 1910 women. The number of GDM women increased significantly each year over the course of the study, as did the proportion requiring insulin therapy. Birth weight and birth weight Z-score fell significantly over the years largely due to a decrease in large for gestational age frequency from 29% to around 19%. CONCLUSION: During the last 13 years, the number of women diagnosed with GDM has increased. Furthermore, the proportion of GDM women receiving insulin treatment has increased. The birth weight in diet-treated women has been virtually normal for the last 5 years of the reported period.

Parity and type 2 diabetes mellitus: a study of insulin resistance and ß-cell function in women with multiple pregnancies.

OBJECTIVE: Increasing parity may be a risk factor for the development of type 2 diabetes mellitus and the metabolic alterations during a normal pregnancy induces a prediabetic state; thus, multiple pregnancies may act as a risk factor for development of type 2 diabetes if these physiological alterations in glucose homeostasis are not reversed postpartum. We hypothesize that multiple pregnancies may lead to ß-cell exhaustion and that the insulin resistance that occurs during pregnancy may persist after multiple births. RESEARCH DESIGN AND MEASURES: A total of 28 healthy premenopausal women were recruited: 15 high parity women (≥4 children) and 13 body mass index (BMI)-matched and age-matched low parity women (1 and 2 children). The study consisted of an intravenous glucose tolerance test for assessment of ß-cell function followed by a hyperinsulinemic euglycemic clamp for assessment of insulin sensitivity. Dual-energy X-ray absorptiometry was performed to assess body composition. RESULTS: All anthropometric measures, measures of body composition and baseline blood samples were comparable between the 2 groups. Neither first phase insulin release (0-10 min, p=0.92) nor second phase insulin release (10-60 min, p=0.62), both measured as area under the curve, differed between the 2 groups. The M-value, calculated as the mean glucose infusion rate during the last 30 min of the clamp period, was 8.66 (7.70 to 9.63) mg/kg/min in the high parity group compared with 8.41 (7.43 to 9.39) mg/kg/min in the low parity group (p=0.69). CONCLUSIONS: We did not detect any effects of increasing parity on insulin sensitivity or ß-cell function.

Posterior reversible encephalopathy syndrome postpartum.

Preeclampsia (PE) should be considered in women with headache who are in gestational week 20 or more, are in labor, or have recently given birth. Early diagnosis is essential to arrest disease progression and further prognosis in PE.

Maternal and neonatal outcomes in pregnancies complicated by gestational diabetes. a nation-wide study.

OBJECTIVE: To estimate the association between gestational diabetes mellitus (GDM) and adverse pregnancy and neonatal outcomes in Denmark. METHODS: A population-based cohort study including all singleton pregnancies in Denmark from 2004 to 2010 (n = 403 092). Maternal complications during pregnancy and delivery and fetal complications were classified according to the International Classification of Diseases 10th Revision. RESULTS: The final study population consisted of 398 623 women. Of these, 9014 (2.3%) had GDM. Data were adjusted for maternal age, parity, smoking, gestational age, birth weight, BMI, gender of the fetus and calendar year. The risk of preeclampsia, caesarean section (both planned and emergency) and shoulder dystocia was increased in women with GDM. In the unadjusted analysis, the risk of thrombosis was increased by a factor 2 in the GDM patients, but in the adjusted analysis this association disappeared. Post-partum hemorrhage was similar in the two groups. The GDM women had an increased risk of giving birth to a macrosomic neonate although the unadjusted analysis did not show any difference between the two groups. Low Apgar score was increased in the GDM, but this association disappeared in the adjusted analysis. Stillbirth was comparable in the two groups. CONCLUSIONS: Women with GDM still have increased incidence of obstetric and neonatal complications, which could imply that treatment of women with GDM should be tightened.