Publications by authors named "Jens Fuglsang"

45 Publications

Postprandial interval walking - effect on blood glucose in pregnant women with gestational diabetes.

Am J Obstet Gynecol MFM 2021 Jun 30:100440. Epub 2021 Jun 30.

Department of Obstetrics and Gynecology, Aarhus University Hospital. Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark.

Background: During pregnancy, postprandial hyperglycemia may increase the risk of complications such as fetal macrosomia. However, evidence on beneficial effects of physical activity on postprandial hyperglycemia is sparse.

Objective: To investigate the effect of 20 minutes of postprandial interval walking on glycemic control and glycemic variability in pregnant women diagnosed with gestational diabetes mellitus.

Study Design: A crossover controlled trial including 14 pregnant women (gestational age 31.8 ± 1.3 weeks) diagnosed with gestational diabetes mellitus (75 gram oral glucose load with 2-hour venous plasma glucose ≥ 9.0 mmol/L) was conducted. Participants completed a 4-day intervention period and a 4-day control period with three days in between. In each study period, participants received a fixed and identical diet. In the intervention period, participants engaged in 20 minutes of postprandial interval walking after breakfast, lunch and dinner. Interval walking comprised alternating three minutes slow and fast intervals. Interstitial glucose concentrations were determined during both study periods with a continuous glucose monitor. The mixed effects model was used to compare differences between exercise and no exercise.

Results: Twenty minutes of postprandial interval walking significantly reduced glycemic control during daytime hours relative to the control period (4-day mean glucose 5.31 (5.04 to 5.59) vs. 5.53 (5.25 to 5.81) mmol/L (95.6 (90.7 to 100.6) vs. 99.5 (94.5 to 104.6) mg/dl); p < 0.05). On each individual trial day, interval walking significantly reduced glycemic control during daytime hours on day 1 (mean glucose 5.19 (4.92 to 5.47) vs. 5.55 (5.27 to 5.83) mmol/L (93.4 (88.6 to 98.5) vs. 99.9 (94.9 to 104.9) mg/dl); p = 0.00), day 2 (mean glucose 5.32 (5.05 to 5.60) vs. 5.57 (5.29 to 5.84) mmol/L (95.8 (90.9 to 100.8) vs. 100.3 (95.2 to 105.1) mg/dl); p = 0.00 and day 3 (mean glucose 5.27 (5.00 to 5.54) vs. 5.46 (5.19 to 5.74) mmol/L (94.9 (90.0 to 99.7) vs. 98.3 (93.4 to 103.3) mg/dl); p = 0.00), but not on day 4.

Conclusion: Twenty minutes of postprandial interval walking appears to be an effective way to control postprandial glucose excursions in women with gestational diabetes mellitus.
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http://dx.doi.org/10.1016/j.ajogmf.2021.100440DOI Listing
June 2021

Extreme insulin resistance during pregnancy: a therapeutic challenge.

Endocrinol Diabetes Metab Case Rep 2021 Jul 1;2021. Epub 2021 Jul 1.

Department of Obstetrics and Gynecology, Department of Diabetes and Endocrinology, Aarhus University Hospital, Palle Juul Jensens Boulevard, Aarhus N, Denmark.

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.
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http://dx.doi.org/10.1530/EDM-20-0191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284943PMC
July 2021

Anti-Xa Monitoring of Low-Molecular-Weight Heparin during Pregnancy: A Systematic Review.

Semin Thromb Hemost 2021 Jun 15. Epub 2021 Jun 15.

Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.

Low-molecular-weight heparin (LMWH) is commonly used for preventing or treating venous thromboembolic disease (VTE) during pregnancy. The physiological changes in maternal metabolism have led to discussions on optimal LMWH dosing strategy and possible need for monitoring. The aim of this systematic review is to summarize and discuss whether LMWH dose adjustment according to anti-Xa provides superior effectiveness and safety compared with weight adjusted or fixed dosed LMWH in pregnant women. A systematic literature search was performed in PubMed, Embase, and Scopus on September 26, 2020. The study is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Effectiveness was defined as episodes of thrombosis and safety as bleeding episodes. In total, 33 studies were included: 4 randomized controlled studies and 29 cohort studies. Prophylactic dosing strategies employing weight dosed, fixed dosed, or anti-Xa adjusted LMWH dosing performed equal in effectiveness and safety. In pregnant women with VTE or high thromboembolic risk, therapeutic weight-adjusted LMWH and weight plus anti-Xa-adjusted LMWH provided equal results in terms of effectiveness and safety. Pregnant women with mechanical heart valves (MHVs) received therapeutic anti-Xa-adjusted LMWH with four out of seven studies presenting mean peak anti-Xa within target ranges. Still, pregnant women with MHV experienced both thrombosis and bleeding with anti-Xa in target. Based on the results of this systematic review, current evidence does not support the need for anti-Xa monitoring when using LMWH as thromboprophylaxis or treatment during pregnancy. Nonetheless, the need for anti-Xa monitoring in pregnant women with MHV may need further scrutiny.
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http://dx.doi.org/10.1055/s-0041-1726374DOI Listing
June 2021

Intrahepatic cholestasis of pregnancy: Association with glycaemic control in gestational diabetes.

Diabet Med 2021 Aug 7;38(8):e14574. Epub 2021 Apr 7.

Department of Clinical Medicine, Aarhus University Hospital, Aarhus N, Denmark.

Aims: The aim of this study was to determine whether the metabolic glucose profile, based on glycaemic control and insulin requirements, was different in women with gestational diabetes mellitus (GDM) and intrahepatic cholestasis of pregnancy (ICP) compared to women with only GDM.

Methods: This retrospective cohort study comprised women with GDM and ICP matched with women with only GDM was undertaken at Aarhus University hospital, Denmark, from 2012 to 2019. A total of 46 cases and 184 controls were compared in relation to glycaemic control during pregnancy. Women with GDM and ICP were further divided into subgroups according to the severity of ICP: mild ICP (fasting bile salts 10-39 μmol/L) and moderate/severe ICP (bile salts ≥40 μmol/L).

Results: No statistically significant differences were observed in baseline 2-h oral glucose tolerance test values, second and third trimester HbA values, or maximum insulin requirements during pregnancy between women with GDM with and without ICP. Significantly more women with ICP developed preeclampsia during pregnancy: 23.9% (11/46) versus 7.6% (14/184); p = 0.003.

Conclusions: This study is the first to address the course of pregnancy in women with GDM with and without ICP in a clinical setting. Under the current treatment guidelines, ICP is not associated with clinically significant changes in glycaemic control in GDM. Significantly more women with both GDM and ICP developed preeclampsia.
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http://dx.doi.org/10.1111/dme.14574DOI Listing
August 2021

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

Cell Metab 2021 May 25;33(5):939-956.e8. Epub 2021 Mar 25.

Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.cmet.2021.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103776PMC
May 2021

Risk of recurrent acute fatty liver of pregnancy: survey from a social media group.

Am J Obstet Gynecol MFM 2020 05 9;2(2):100085. Epub 2020 Jan 9.

Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark.

Background: Acute fatty liver of pregnancy is a rare but serious complication in the last trimester of pregnancy or postpartum period. Data on the recurrence risk are largely unavailable, as only case reports or very small case series exist in which only 1 woman had recurrent acute fatty liver of pregnancy.

Objective: We aimed to estimate the risk of acute fatty liver of pregnancy recurrence and to compare disease severity and gestational age between primary and recurrent disease using patient-provided data from an acute fatty liver of pregnancy social media patient group.

Materials And Methods: We developed and distributed an electronic questionnaire through an international Facebook group called "Acute Fatty Liver of Pregnancy." The data collection took place from June 11, 2018, to August 17, 2018, using REDCap. Our main outcome measures were recurrence of acute fatty liver of pregnancy, severity with recurrence, and gestational age at delivery.

Results: A total of 69 women with previous acute fatty liver of pregnancy completed the questionnaire; 24 women had a subsequent delivery, of whom 5 women were diagnosed with acute fatty liver of pregnancy again. In 4 of 5 of these women (80%), acute fatty liver of pregnancy took a milder course, whereas in 1 woman it worsened in the next pregnancy. Women with acute fatty liver of pregnancy recurrence delivered at a median gestational age at 265 days (interquartile range, 242-287 days) in their first pregnancy with acute fatty liver of pregnancy as compared to delivery by a prelabor cesarean delivery at 245 days (interquartile range, 235-261 days) in their second pregnancy with acute fatty liver of pregnancy. Male fetal sex was not associated with an increased risk of recurrent acute fatty liver of pregnancy.

Conclusion: One in 5 women reported having had recurrent acute fatty liver of pregnancy, with most cases being milder, possibly because of an earlier gestational age at delivery.
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http://dx.doi.org/10.1016/j.ajogmf.2020.100085DOI Listing
May 2020

Maternal prepregnancy body mass index and physical activity during pregnancy assessed by accelerometer.

Am J Obstet Gynecol MFM 2020 11 22;2(4):100182. Epub 2020 Jul 22.

Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark.

Background: Maternal prepregnancy overweight and obesity increase the risk of adverse pregnancy outcomes, whereas physical activity during pregnancy has a beneficial effect on both the mother and the fetus. Limited data are available on how maternal prepregnancy overweight and obesity affect physical activity during pregnancy.

Objective: The purpose of this study was to describe the association between prepregnancy body mass index and physical activity during pregnancy.

Study Design: An observational prospective cohort study of 400 singleton pregnant women who were attending routine antenatal care at Aarhus University Hospital, Denmark (2010-2015), was conducted. Physical activity was assessed by an accelerometer (SenseWear Armband) for 7 days for each trimester. Participants were stratified in 3 different groups of prepregnancy body mass index: normal weight (body mass index <25 kg/m), overweight (body mass index 25-29.9 kg/m), and obese (body mass index ≥30 kg/m). Physical activity was measured as the number of steps per day, metabolic equivalent of task per day, time in moderate- to vigorous-intensity physical activity (>3 metabolic equivalent of task), and time in vigorous-intensity physical activity (>6 metabolic equivalent of task). Linear regression and multilevel mixed-effects models were used to explore the association between prepregnancy body mass index and physical activity variables during pregnancy.

Results: We found an inverse linear relationship between prepregnancy body mass index and both mean number of steps per day and mean metabolic equivalent of task per day (P<.001). At baseline, women with normal weight walked a median of 1214 steps per day (95% confidence interval, 576-1852) more than women who were obese (P<.05), and women who were overweight walked a median of 948 steps per day (95% confidence interval, 218-1677) more than women who were obese (P<.05). Independent of prepregnancy body mass index, all variables of physical activity decreased over the course of pregnancy (P<.05), with the greatest decrease in the third trimester.

Conclusion: Maternal physical activity measured by an accelerometer decreased across pregnancy independent of maternal body mass index status and was inversely associated with prepregnancy body mass index. Thus, being overweight or obese before pregnancy increased the risk of sedentary behavior during pregnancy.
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http://dx.doi.org/10.1016/j.ajogmf.2020.100182DOI Listing
November 2020

Changes in insulin sensitivity and insulin secretion during pregnancy and post partum in women with gestational diabetes.

BMJ Open Diabetes Res Care 2020 10;8(2)

Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.

Introduction: The metabolic abnormalities underlying gestational diabetes mellitus (GDM) include increased insulin resistance and beta cell defects, but it is essential to clarify how insulin resistance and insulin secretion develop post partum in order to decide when and how to screen for type 2 diabetes. The purpose of the present study was to characterize and compare changes in insulin sensitivity, insulin secretion and hormonal status around parturition and 6 months post partum in women with gestational diabetes.

Research Design And Methods: A longitudinal experimental study was performed at Aarhus University Hospital, Denmark. Eight women with GDM were examined at three identical visits: in late pregnancy (LP) between gestational age 34+0 and 36+6, early post partum (EPP) between 12 and 34 days post partum, and late post partum (LPP) 6 months post partum. An intravenous glucose tolerance test was performed, followed by a hyperinsulinemic euglycemic clamp. Blood samples were collected to assess metabolic, hormonal and inflammatory markers at each visit.

Results: First and second phase insulin secretion and C-peptide concentrations were higher in late pregnancy than post partum (p<0.001). Insulin sensitivity index (ISI) was different at all three visits: ISI=0.03±0.004, ISI=0.09±0.008 and ISI=0.07±0.008) (p<0.001). Also, significant changes in lipids, leptin, glucagon, growth hormone and insulin-like growth factor-1 were seen when comparing the visits.

Conclusions: Insulin sensitivity improves immediately after delivery in women with GDM but seems to deteriorate within the first 6 months post partum. Our findings underline the importance of having an increased awareness of the profound risk of developing type 2 diabetes after GDM.

Trial Registration Number: NCT02770079.
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http://dx.doi.org/10.1136/bmjdrc-2020-001728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594208PMC
October 2020

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

Nutrients 2020 Oct 6;12(10). Epub 2020 Oct 6.

Department of Obstetrics and Gynaecology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark.

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.
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http://dx.doi.org/10.3390/nu12103050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599681PMC
October 2020

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

J Diabetes 2020 Nov 18;12(11):798-806. Epub 2020 Jun 18.

Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus N, Denmark.

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.
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http://dx.doi.org/10.1111/1753-0407.13070DOI Listing
November 2020

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

Appl Physiol Nutr Metab 2020 Nov 22;45(11):1247-1252. Epub 2020 May 22.

Department of Obstetrics and Gynecology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N., Denmark.

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/m 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 ( = 0.002). Similarly, mean glucose peak level was significantly lower after cycling compared with after rest ( 0.039). Lower levels of insulin and C-peptide were observed after 1 h ( < 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. 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.
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http://dx.doi.org/10.1139/apnm-2020-0020DOI Listing
November 2020

Determinants of Maternal Insulin Resistance during Pregnancy: An Updated Overview.

J Diabetes Res 2019 19;2019:5320156. Epub 2019 Nov 19.

Department of Obstetrics and Gynecology, Aarhus University Hospital, 8200 Aarhus N, Denmark.

Insulin resistance changes over time during pregnancy, and in the last half of the pregnancy, insulin resistance increases considerably and can become severe, especially in women with gestational diabetes and type 2 diabetes. Numerous factors such as placental hormones, obesity, inactivity, an unhealthy diet, and genetic and epigenetic contributions influence insulin resistance in pregnancy, but the causal mechanisms are complex and still not completely elucidated. In this review, we strive to give an overview of the many components that have been ascribed to contribute to the insulin resistance in pregnancy. Knowledge about the causes and consequences of insulin resistance is of extreme importance in order to establish the best possible treatment during pregnancy as severe insulin resistance can result in metabolic dysfunction in both mother and offspring on a short as well as long-term basis.
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http://dx.doi.org/10.1155/2019/5320156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885766PMC
June 2020

Double-balloon catheter for induction of labor in 362 women with and without prior cesarean section.

Eur J Obstet Gynecol Reprod Biol X 2019 Oct 1;4:100033. Epub 2019 May 1.

Department of Gynecology and Obstetrics, Aarhus University Hospital, Aarhus N, Denmark.

Objective: Balloon catheter is the preferred method for induction of labor in women with prior cesarean section. We sought to evaluate the rate of vaginal delivery, induction-delivery time and outcome predictors after induction with double-balloon catheter.

Study Design: We conducted a retrospective cohort study including women with prior cesarean section undergoing induction of labor with a double-balloon catheter during the period January 2007-June 2014 at a large, tertiary Danish university hospital. For comparison, we included women with no prior cesarean section undergoing induction with double-balloon catheter after failed medical induction. Inclusion criteria were singleton pregnancy, an unfavorable cervix, intact membranes, cephalic presentation and either previous cesarean section or failed medical induction of labor. Exclusion criteria included contraindications for vaginal delivery, severe fetal malformation and stillbirth. Study subjects were identified in a local computerized system and data extracted from the medical records.

Results: Women with prior cesarean section ( = 304 induced with double-balloon catheter had a vaginal delivery rate of 50.3% (95% CI 44.7-55.9) compared to 51.7% (95% CI 39.2-64.1) in women with no prior cesarean section but preceding failed medical induction of labor ( = 58) ( = 0.85). BMI≥30 was associated with increased frequency of cesarean section. Median time from induction to vaginal delivery was 27.1(20.4-31.1) hours and 28.4(25.5-36.1) hours, respectively ( = 0.05). The rate of complete uterine rupture was 1.0%.

Conclusions: Similar success rates of approximately 50% for vaginal delivery were observed after induction of labor with a double-balloon catheter in women with and without prior caesarean section. A BMI ≥ 30 was associated with an increased frequency of caesarean section.
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http://dx.doi.org/10.1016/j.eurox.2019.100033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817684PMC
October 2019

[Pregnancy underweight - an overlooked risk factor].

Ugeskr Laeger 2019 Sep;181(40)

Underweight, defined as BMI ≤ 18.5 kg/m2, is found in 4.2% of pregnancies in Denmark. Pre-pregnancy underweight is more often seen in relation to psychiatric disorders, e.g. anorexia nervosa, and diet restrictions and associates with adverse pregnancy outcomes, such as antepartum haemorrhage requiring blood transfusion, preterm birth, small for gestational age infants, and impaired ability to breastfeed. In this review, we recommend identification of possible underlying medical or psychiatric disorders, focus on sufficient gestational weight gain, and relevant vitamin and mineral substitution.
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September 2019

Increased Insulin Requirements in Twin Pregnancy in Type 1 Diabetes.

Diabetes Care 2019 10 9;42(10):e164-e165. Epub 2019 Aug 9.

Department of Obstetrics and Gynaecology, Aarhus University Hospital, Aarhus, Denmark

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http://dx.doi.org/10.2337/dc19-0859DOI Listing
October 2019

Platelet function in preeclampsia - a systematic review and meta-analysis.

Platelets 2019 14;30(5):549-562. Epub 2019 Apr 14.

a Centre for Haemophilia and Thrombosis, Department of Clinical Biochemistry , Aarhus University Hospital , Aarhus , Denmark.

Preeclampsia is a serious pregnancy-related complication. Platelets are potentially important in the pathogenesis of preeclampsia, and platelet function analyses may prove as sensitive preeclampsia biomarkers. This study aimed to systematically review and summarise the literature on platelet function markers in preeclampsia. This systematic review was conducted according to PRISMA and registered in PROSPERO. Relevant studies were identified through PubMed and Embase on 15/08/17. As platelet function markers platelet activation, platelet aggregation and platelet adhesion markers were included. If possible, relevant data were extracted for each marker to perform a meta-analysis of the mean difference between women with and without preeclampsia. All 69 included articles underwent quality rating. Some platelet activation markers, especially p-selectin and mean platelet volume (MPV), were significantly increased comparing the two groups of women, while others were not. The meta-analysis demonstrated that, overall, women with preeclampsia had significantly higher MPV than in women without preeclampsia. No significant difference was found regarding platelet aggreg`ation comparing the two groups. Platelet adhesion was investigated in noneof the included studies. In conclusion, further studies are warranted to investigate platelet activation markers future role as predictive markers in preeclampsia. MPV is suggested as the most promising biomarker for evaluating platelet function in preeclampsia.
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http://dx.doi.org/10.1080/09537104.2019.1595561DOI Listing
November 2019

Diabetes Mellitus and lower genital tract tears after vaginal birth: A cohort study.

Midwifery 2019 Feb 22;69:121-127. Epub 2018 Nov 22.

Department of Obstetrics and Gynaecology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200, Denmark; Department of Clinical Medicine, Aarhus University, Incuba / Skejby Building 2 Palle Juul-Jensens Boulevard 82, Aarhus DK-8200, Denmark. Electronic address:

Introduction: Diabetes Mellitus in pregnancy is increasing. No existing studies have examined Diabetes Mellitus as the primary exposure for lower genital tract tears after vaginal birth. The objective was to study the association between Diabetes Mellitus (all types combined), Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus and Gestational Diabetes Mellitus and lower genital tract tears after vaginal birth.

Material And Methods: A register-based cohort study of women with singleton pregnancy and without a previous cesarean section at near-term (≥ 35 + 0 weeks) and term (≥ 37 + 0 weeks) gestational age, n = 31,297 at Aarhus University Hospital, Denmark from 1 January 2004 to 31 December 2012. The associations between Diabetes Mellitus and lower genital tract tears were analysed using a fixed multiple logistic regression analyses.

Results: Approximately 32,000 women were eligible for the study; 796 women had diabetes (2.5%) and 1318 experienced anal sphincter injury (4.3%). The overall risk of lower genital tract tears was similar among women with a diagnosis of diabetes (Type1 Diabetes Mellitus, Type 2 Diabetes Mellitus, and Gestational Diabetes Mellitus) compared to women without diabetes, except for nulliparous women with Type1 Diabetes Mellitus who experienced a higher risk of episiotomies, crude and adjusted odds ratios (OR 2.13, 95% CI 1.14-3.97) and (OR 2.48, 95% CI 1.21-5.10), respectively.

Conclusions: Women with Diabetes Mellitus without a previous cesarean section who gave birth vaginally to a single child at term or near term did not experienced an increased risk of lower genital tract tears. However, nulliparous women with Type 1 Diabetes Mellitus experienced a higher risk of episiotomy. These results may be used to individualised counselling of women with Diabetes Mellitus regarding mode of birth and may reduce worries about genital tract tears in women with Diabetes Mellitus considering vaginal birth.
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http://dx.doi.org/10.1016/j.midw.2018.11.010DOI Listing
February 2019

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

J Diabetes Res 2018 15;2018:5937059. Epub 2018 Mar 15.

Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.

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.
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http://dx.doi.org/10.1155/2018/5937059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875052PMC
October 2018

Parity Increases Insulin Requirements in Pregnant Women With Type 1 Diabetes.

J Clin Endocrinol Metab 2018 06;103(6):2302-2308

Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark.

Context: Tight glycemic control throughout pregnancy in women with type 1 diabetes is crucial, and knowledge about which factors that affect insulin sensitivity could improve the outcome for both mother and offspring.

Objective: To evaluate insulin requirements in women with type 1 diabetes during pregnancy and test whether parity affects insulin requirements.

Design: Observational cohort study consisting of women with type 1 diabetes who gave birth at Aarhus University Hospital, Denmark, from 2004 to 2014.

Main Outcome Measure: Daily insulin requirement (the hypothesis that parity could affect insulin resistance was formulated before data collection).

Results: A total of 380 women with a total of 536 pregnancies were included in the study. Mean age was 31.1 years, and prepregnancy hemoglobin A1c was 60 mmol/mol. Parity was as follows: P0, 43%; P1, 40%; P2, 14%; and P3+4, 3%. Insulin requirements from weeks 11 to 16 decreased significantly by 4% (P = 0.0004) and rose from week 19 to delivery with a peak of 70% (P < 0.0005) at weeks 33 to 36. Overall, insulin requirements increased significantly with parity. The unadjusted differences between P0 and P1, P2, and P3+4 were 9% (P < 0.0005), 12% (P < 0.0005), and 23% (P < 0.0011), respectively. After adjustment for confounders, differences were 13% (P < 0.0005), 20% (P < 0.0005), and 36% (P < 0.0005). We also observed an adjusted difference between P1 and P3+4 of 20% (P < 0.0012).

Conclusions: The data show changes in insulin requirements from week to week in pregnancy and indicate that insulin requirements increase with parity. This suggests that the patient's parity probably should be considered in choosing insulin dosages for pregnant women with type 1 diabetes.
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http://dx.doi.org/10.1210/jc.2018-00094DOI Listing
June 2018

Ovarian vein thrombosis after delivery.

Hamostaseologie 2018 02 26;38(1):9-10. Epub 2018 Feb 26.

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http://dx.doi.org/10.5482/HAMO-17-09-0032DOI Listing
February 2018

Urine albumin is a superior predictor of preeclampsia compared to urine plasminogen in type I diabetes patients.

J Am Soc Hypertens 2018 02 13;12(2):97-107. Epub 2017 Dec 13.

Department of Gynecology and Obstetrics, Institute of Clinical Medicine, Aarhus University Hospital Skejby, Denmark.

Pregnant women with type I diabetes mellitus (T1DM) are at increased risk of developing preeclampsia (PE). Plasminogen is aberrantly filtrated from plasma into tubular fluid in PE patients and activated to plasmin. Plasmin activates the epithelial sodium channel in the collecting ducts potentially causing impaired sodium excretion, suppression of the renin-angiotensin-aldosterone system, and hypertension in PE. The objective of the study was to test whether urinary total plasmin(ogen)/creatinine ratio and plasma concentration of aldosterone were better predictors of PE in pregnant women with T1DM compared with urine albumin and haemoglobin A. The design was a longitudinal observational study of 88 pregnant T1DM patients at 2 Danish centers. Spot urine- and blood samples were collected at gestational weeks 12, 20, 28, 32, and 36. U-plasmin(ogen)/creatinine ratio increased during pregnancy. In gestational week 36, the ratio was significantly increased in the T1DM patients developing PE (P < .05). P-aldosterone was significantly increased in gestational week 20 in the group developing PE (P < .05). U-albumin/creatinine ratio was significantly increased and predicted PE at all tested gestational ages. U-albumin/creatinine ratio had a stronger association with the development of PE compared to u-total plasmin(ogen)/creatinine ratio and p-aldosterone. The positive association between u-total plasmin(ogen) and development of PE late in pregnancy is compatible with involvement in PE pathophysiology. The significance of albumin in urine emphasizes the importance of preventing renal complications when planning pregnancy in patients with type I diabetes.
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http://dx.doi.org/10.1016/j.jash.2017.12.003DOI Listing
February 2018

Microvascular disease during pregnancy in type 1 diabetes is associated with ambulatory arterial stiffness.

Pregnancy Hypertens 2018 Apr 23;12:150-154. Epub 2017 Nov 23.

Department of Obstetrics/Gynecology, Herning, Herning Hospital, Gl. Landevej 61, DK-7400 Herning, Denmark; Department of Obstetrics/Gynecology, Aarhus, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark.

Objectives: The objective of this study was to evaluate the association between the ambulatory arterial stiffness index (AASI) and markers of microvascular disease during pregnancy in women with type 1 diabetes.

Study Design: A total of 151 women with type 1 diabetes mellitus were recruited for repeat 24-h BP recordings thrice during pregnancy and once three months post partum. Fifty women without diabetes served as controls. The AASI and pulse pressure (PP) were computed from blood pressure recordings. Repeated measures analysis of variance was used for comparison between groups during and after pregnancy. Linear regression analysis was performed with AASI and PP as dependent variables and albuminuria and retinopathy as independent variables.

Main Outcome Measures: AASI during diabetic pregnancy and association with microvascular disease.

Results: Micro- or macroalbuminuria was present in 23% of the women and 58% had either simplex or proliferative retinopathy. The AASI was inversely associated with the coefficient of determination, which means that the stiffer vascular wall the more random variability in BP.

Conclusion: AASI showed a strong association with microvascular disease during pregnancy in women with type 1 diabetes. Together with the flattened circadian rhythm this indicates a pregnancy-related functional change in the vascular bed.
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http://dx.doi.org/10.1016/j.preghy.2017.11.011DOI Listing
April 2018

Preeclampsia is associated with increased ambulatory arterial stiffness index in type 1 diabetes mellitus.

Eur J Obstet Gynecol Reprod Biol 2017 Sep 25;216:153-158. Epub 2017 Jul 25.

Department of Obstetrics/Gynecology, Herning Hospital, Denmark; Department of Obstetrics/Gynecology and Clinical Institute, Aarhus University Hospital, Denmark.

Introduction: Treatment of mild to moderate hypertension might not benefit maternal or fetal outcome. This pessimistic point of view may have come about by using non-validated methods for measuring blood pressure in pregnancy combined with inadequate methodology for diagnosis, treatment, and monitoring effects.

Aim: To determine the association between AASI in women with type 1 diabetes mellitus (T1DM) and preeclampsia, and to assess the ability of AASI to diagnose preeclampsia.

Material And Methods: Repeated 24-h ambulatory blood pressure recordings were performed three times during pregnancy and once three months postpartum in 151 women with T1DM and 50 control women without diabetes. Circadian rhythm was evaluated as the night day ratio, night blood pressure divided by day blood pressure.

Results: Of the T1DM women, 33 developed preeclampsia, which was associated with AASI in the 3rd trimester (p<0.05). The best predictor of preeclampsia in T1DM was an AASI of 0.35. The diurnal blood pressure was significantly higher in all trimesters in women who later had preeclampsia. A flattened circadian rhythm was present in T1DM women with preeclampsia compared to women without preeclampsia (night-day ratio: systole 2nd trimester: 0.94±0.07 vs. 0.91±0.05, women with and without preeclampsia, respectively, p=0.015; diastole 2nd trimester: 0.89±0.07 vs. 0.85±0.07, p=0.003). AASI was higher during pregnancy compared to postpartum in women with T1DM (0.31±0.16, 0.31±0.16 and 0.33±0.18 vs. 0.25±0.17; 1st, 2nd and 3rd trimester vs. postpartum).

Conclusion: Women with T1DM and preeclampsia demonstrate increased arterial stiffness and had early manifestations in the non-dipping of blood pressure.
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http://dx.doi.org/10.1016/j.ejogrb.2017.07.030DOI Listing
September 2017

IGF-1 is associated with fetal growth and preterm delivery in type 1 diabetic pregnancy.

Gynecol Endocrinol 2016 Jun 13;32(6):488-91. Epub 2016 Jan 13.

b Aarhus University Hospital , Aarhus , Denmark.

Aim: No data on IGF-1 and either preterm or preeclampsia have been reported so far in diabetic pregnancies. We evaluated consecutive measurements of IGF-1 for preeclampsia, preterm delivery and birth weight in type 1 diabetic pregnancy.

Setting: In an outpatient university clinic, 97 pregnant women were consecutively recruited for evaluation of indicators for deterioration of diabetes status and adverse perinatal outcome. At every visit, a blood sample for measurement of IGF-1 was drawn.

Results: IGF-1 levels from week 14 to 32 was consistently lower in women who delivered preterm compared with women whose delivered after gestational week 36; the increase in 2nd and 3rd trimester was steeper in those delivering at term than in women delivering preterm (p = 0.032). IGF-1 in preeclampsia did not show the same relation in diabetic women (p = 0.74). The lowest tertile of birth weight ratio (0.8-1.2) was associated with lower IGF-1 from week 14 to 32 (p = 0.047, adjusted for preterm delivery and preeclampsia).

Conclusion: We found low IGF-1 levels associated with preterm delivery and low birth weight.
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http://dx.doi.org/10.3109/09513590.2015.1134477DOI Listing
June 2016

Perfluoroalkyl Acid Concentrations in Blood Samples Subjected to Transportation and Processing Delay.

PLoS One 2015 10;10(9):e0137768. Epub 2015 Sep 10.

Research Unit for Obstetrics and Gynecology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.

Background: In studies of perfluoroalkyl acids, the validity and comparability of measured concentrations may be affected by differences in the handling of biospecimens. We aimed to investigate whether measured plasma levels of perfluoroalkyl acids differed between blood samples subjected to delay and transportation prior to processing and samples with immediate processing and freezing.

Methods: Pregnant women recruited at Aarhus University Hospital, Denmark, (n = 88) provided paired blood samples. For each pair of samples, one was immediately processed and plasma was frozen, and the other was delayed and transported as whole blood before processing and freezing of plasma (similar to the Danish National Birth Cohort). We measured 12 perfluoroalkyl acids and present results for compounds with more than 50% of samples above the lower limit of quantification.

Results: For samples taken in the winter, relative differences between the paired samples ranged between -77 and +38% for individual perfluoroalkyl acids. In most cases concentrations were lower in the delayed and transported samples, e.g. the relative difference was -29% (95% confidence interval -30; -27) for perfluorooctane sulfonate. For perfluorooctanoate there was no difference between the two setups [corresponding estimate 1% (0, 3)]. Differences were negligible in the summer for all compounds.

Conclusions: Transport of blood samples and processing delay, similar to conditions applied in some large, population-based studies, may affect measured perfluoroalkyl acid concentrations, mainly when outdoor temperatures are low. Attention to processing conditions is needed in studies of perfluoroalkyl acid exposure in humans.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0137768PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565678PMC
May 2016

Pregnancy and delivery in a woman with type 1 diabetes, gastroparesis, and a gastric neurostimulator.

Diabetes Care 2015 May;38(5):e75

Obstetrics and Gynaecology Department Y, Aarhus University Hospital, Aarhus, Denmark.

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http://dx.doi.org/10.2337/dc14-2959DOI Listing
May 2015

Later reproductive health after B-Lynch sutures: a follow-up study after 10 years' clinical use of the B-Lynch suture.

Authors:
Jens Fuglsang

Fertil Steril 2014 Apr 15;101(4):1194-9. Epub 2014 Feb 15.

Obstetrics and Gynecology Department Y, Aarhus University Hospital, Aarhus, Denmark. Electronic address:

Objective: To evaluate the reproductive prognosis after having a B-Lynch suture placed previously.

Design: Follow-up study based on patients' records.

Setting: University hospital setting (level three; 4,800 deliveries per year).

Patient(s): All patients registered to have had a B-Lynch suture placed from 2002 to 2012.

Intervention(s): None.

Main Outcome Measure(s): Future pregnancies.

Result(s): Forty-four B-Lynch procedures were identified in 43 women. Twenty-six were primiparas at the time of B-Lynch suture. Follow-up took place a median 45 months (range, 17-126 months) after B-Lynch suture placement; one woman was lost to follow-up. Overall, 16 of 42 women obtained a new pregnancy. Among primiparas, 44% either had an ongoing pregnancy or a delivery. Among women not having a succeeding pregnancy, one woman had a peripartum hysterectomy, one was advised against pregnancy, one developed Asherman's syndrome, and three women were known to attempt to obtain pregnancy. In deliveries after a previous B-Lynch suture, 3 of 13 women had estimated bleeding above 1,000 mL, and 2 of these had severe bleeding. A time trend was observed indicating that B-Lynch sutures are placed increasingly often.

Conclusion(s): The reproductive prognosis after a B-Lynch suture has been placed seems to be relatively good. Nonetheless, complications that might influence future pregnancy may occur, and advice given should address this.
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http://dx.doi.org/10.1016/j.fertnstert.2014.01.015DOI Listing
April 2014

Ambulatory arterial stiffness index in type 1 diabetes mellitus: any different during pregnancy?

Eur J Obstet Gynecol Reprod Biol 2013 Jul 28;169(2):234-8. Epub 2013 May 28.

Department of Obstetrics/Gynaecology, Herning Hospital, Denmark.

Objective: To analyze the ambulatory arterial stiffness index (AASI) and pulse pressure (PP) during pregnancy and 3 months after delivery in type 1 diabetes mellitus (T1DM) and compare it to healthy pregnant controls.

Study Design: Prospective, descriptive study of 59 women with T1DM and 42 non-diabetic women. Blood pressure was measured using a portable oscillometry monitor and AASI was calculated as 1 minus the regression slope of diastolic on systolic blood pressure obtained from 24-h monitoring. Main outcome measures were comparisons of the AASI and PP between T1DM women and controls examined during pregnancy, and of the AASI and PP during and after pregnancy in T1DM women.

Results: PP and AASI were higher at all times during pregnancy in T1DM compared to postpartum (p<0.01). AASI and PP were significantly associated with albumin excretion rate when adjusting for retinopathy, preeclampsia, duration of diabetes, HbA1c, age, and BMI. The AASI was positively correlated with night-day ratio in the 1st and 3rd trimesters during pregnancy. No difference was found in AASI compared with non-diabetic controls during pregnancy.

Conclusions: AASI and PP increased during diabetic pregnancy and were associated with the women's albuminuria grade.
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http://dx.doi.org/10.1016/j.ejogrb.2013.04.010DOI Listing
July 2013

Alterations in circulating adiponectin levels occur rapidly after parturition.

Eur J Endocrinol 2010 Jul 9;163(1):69-73. Epub 2010 Apr 9.

Gynaecological/Obstetrical Research Laboratory, Gynaecological/Obstetrical Department, Clinical Institute, Aarhus University Hospital, Skejby, DK-8200 Aarhus N, Denmark.

Objective: To determine the levels of adiponectin and its subforms before and immediately after delivery to estimate the effect of cessating advanced pregnancy on circulating adiponectin levels.

Design And Methods: In a cohort of 37 women with uncomplicated singleton pregnancies and 6 women with twin pregnancies, serum adiponectin was measured before caesarean section (CS) in the fasting state, and 24 and 48 h after CS.

Results: Serum adiponectin levels declined within 24 h of delivery from median 8.34 mg/l (range 5.57-20.47) to 6.81 mg/l (4.16-17.39) after 24 h and 6.84 mg/l (3.83-17.42) after 48 h. This corresponded to a relative decrease to 83+/-6 and 81+/-7% of pregnant values after 24 and 48 h respectively (P<0.001, ANOVA). In twin pregnancies, maternal adiponectin levels displayed a decrease that was the same as that displayed by them after birth (P<0.001). High-molecular weight adiponectin constituted 50+/-8% (range 34-68%) of total adiponectin. Absolute changes in adiponectin levels after delivery were most pronounced in this subfraction. The percentage medium-molecular weight adiponectin decreased slightly, but significantly (from 37+/-6 to 35+/-5%, P<0.001), and a similar statistically significant rise was observed in the low-molecular weight fraction (from 13+/-2 to 15+/-3%; P<0.001) within 48 h of delivery.

Conclusions: Decreases in adiponectin levels occur shortly after delivery, and adiponectin subforms initiate the changes towards the non-pregnant state.
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http://dx.doi.org/10.1530/EJE-10-0017DOI Listing
July 2010

Ghrelin in pregnancy and lactation.

Authors:
Jens Fuglsang

Vitam Horm 2008 ;77:259-84

Gynaecological/Obstetrical Research Laboratory, Aarhus University Hospital, Skejby Hospital, DK-8200, Aarhus N, Denmark.

Ghrelin and its receptors are found in the reproductive organs and in the placenta, clearly indicating a role for ghrelin in reproduction. Circulating ghrelin levels peak at mid-gestation, then with advancing gestational age declining ghrelin levels are observed. At the same time the maternal organism increases its fat mass, becomes insulin resistant and the growth hormone (GH) axis is dominated by placental growth hormone circulating in concentrations comparable to GH levels observed in acromegaly. After delivery, normalization of ghrelin levels occurs before the maternal fat mass is restored at prepregnant levels. The physiological course of ghrelin during the three trimesters of human pregnancy is discussed, as are the physiological roles ghrelin may subserve. Regulation of maternal energy intake may be the prevailing effect of ghrelin in pregnancy and lactation, but several other effects of ghrelin may coexist, including local effects. Finally, ghrelin secretion in the fetus is briefly discussed.
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http://dx.doi.org/10.1016/S0083-6729(06)77011-XDOI Listing
February 2008
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