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AIM: We investigated the effect of 52-week treatment with liraglutide, a glucagon-like peptide 1 receptor agonist, on glucose tolerance and incretin effect in women with previous gestational diabetes mellitus (pGDM). MATERIALS AND METHODS: Women with overweight/obesity and pGDM were randomized to once daily subcutaneous liraglutide 1.8 mg or placebo for 52 weeks. Participants underwent oral glucose tolerance test (OGTT) and isoglycaemic intravenous glucose infusion at baseline and at 52 weeks, and an additional OGTT after the drug wash-out. RESULTS: In total, 104 women [age: mean ± SD, 38 ± 5 years; fasting plasma glucose (FPG): 5.5 ± 0.4 mmol/L; glycated haemoglobin (HbA1c): 33 ± 4 mmol/mol, bodyweight: 88.2 ± 14.8 kg, body mass index: 31.1 ± 4.3 kg/m2 ] were assigned to liraglutide (n = 49) or placebo (n = 55). Estimated treatment difference (ETD) for area under curve during OGTT was -173 (95% confidence interval -250 to -97) mmol/L × min, p < .0001, but after wash-out the difference disappeared [ETD 58 (-30 to 146) mmol/L × min, p = .536]. Liraglutide reduced FPG [ETD -0.2 (-0.4 to -0.1) mmol/L, p = .018], HbA1c [-2.2 (-3.5 to -0.8) mmol/mol, p = .018] and bodyweight [-3.9 (-6.2 to -1.6) kg, p = .012]. No change in the incretin effect was observed. The number of women with prediabetes was reduced from 64% to 10% with liraglutide vs. 50% with placebo [adjusted odds ratio 0.10 (0.03-0.32), p = .002]. CONCLUSIONS: Treatment with liraglutide for 52 weeks improved glucose tolerance, FPG, HbA1c and bodyweight in women with overweight/obesity and pGDM. Progression to prediabetes while on drug was markedly reduced, but after a 1-week drug wash-out, the effect was lost.

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Objectives: The objective of this analysis was to evaluate the effect of a diet rich in animal protein and low in glycemic index on blood pressure during pregnancy. Design: This post hoc, secondary data analysis of a randomized controlled trial, evaluated blood pressure in pregnant participants who were randomized either to an ad libitum diet with high protein and low glycemic index, rich in dairy and seafood, or an ad libitum control diet according to national recommendations. Setting: The study occurred in pregnant women in Copenhagen, Denmark. Sample: A total of 279 pregnant females with overweight or obesity were enrolled. Methods and outcome measure: Blood pressure was measured at 5 timepoints during pregnancy from gestational week 15 through week 36, and blood pressure between groups was compared. Results: There were no differences between diet arms in systolic or diastolic blood pressure over time. There were also no differences in most blood-pressure-related pregnancy complications, including the prevalence of premature birth, preeclampsia, or hypertension, but the frequency of total cesarean sections was lower in the active than the control group (16 out of 104 vs. 30 out of 104) (p = 0.02). Conclusion: Increased animal protein intake was not associated with changes in blood pressure in pregnant women with overweight or obesity. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT01894139].

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Objective: To examine the association of gestational weight gain (GWG) among women with pre-pregnancy overweight or obesity with infant weight and BMI z-score at birth. Methods: This study is a secondary analysis of a randomized controlled trial including data from 208 infants at birth born by mothers with pre-pregnancy BMI between 28 and 45 kg/m2 who completed the APPROACH study (randomized to a high-protein low-glycemic index diet or a moderate-protein moderate-glycemic index diet). This analysis pooled the two diet treatment groups together and data were analyzed using a linear mixed model. Results: Limiting GWG by 1 kg was associated with lower birthweight (-16 g, P = 0.003), BMI z-score (-0.03SD, P = 0.019), weight z-score (-0.03SD, P = 0.004), and infant abdominal circumference (-0.06 cm, P = 0.039). Infants born by mothers whose GWG was ≤9 kg weighed less (122 g, 95% CI: 6-249, P = 0.040), had similar BMI z-score (0.2SD, 95% CI: -0.06 to 0.55, P = 0.120), and lower incidence of emergency cesarean deliveries (11.5% vs. 23.1%, P = 0.044) compared to infants born by mothers whose GWG was >9 kg. When women were classified into GWG quartiles, women in Q1 (GWG range: -7.0 to 3.2 kg) gave birth to smaller infants (3,420 g, P = 0.015) with lower BMI z-score (-0.5SD, P = 0.041) than women in Q2 (3.3-7.1 kg), Q3 (7.2-10.9 kg) and Q4 (11.1-30.2 kg). Conclusions: Limiting GWG among women with pre-pregnancy overweight or obesity was associated with lower infant weight, BMI z-score, weight z-score, and abdominal circumference at birth. Moreover, GWG below the Institute of Medicine guideline of a maximum of 9 kg was associated with lower birthweight and fewer emergency cesarean deliveries.

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BACKGROUND: Prepregnancy overweight and excessive gestational weight gain (GWG) increase the risk of complications and offspring obesity. OBJECTIVES: We aimed to investigate the effect of a high-protein low-glycemic index (HPLGI) diet on GWG, birth weight, and risk of gestational complications in pregnant women with obesity. METHODS: A total of 279 women with prepregnancy overweight or obesity (BMI: 28-45 kg/m2), between 18 and 45 y old, and in their late first trimester with singleton pregnancies, were randomly assigned to 1 of 2 ad libitum diets: a high-protein low-glycemic index diet (HPLGI: 25%-28% of energy from protein and glycemic index ≤ 55) and a moderate-protein moderate-glycemic index diet (MPMGI: 15%-18% of energy from protein and glycemic index ∼60). Diets were consumed from gestational week 15 and throughout pregnancy. Participants received dietary guidance by a clinical dietician 9 times to facilitate adherence. RESULTS: Out of 141 and 138 women randomly assigned to the HPLGI and MPMGI diets, 105 and 104 completed the intervention, respectively (75%). In the available case analyses, GWG was 6.8 ± 1.3 kg among women assigned the HPLGI diet and this was significantly lower, by -1.7 kg (95% CI: -2.8, -0.5 kg; P = 0.004), than the GWG of 8.5 ± 1.3 kg among women assigned the MPMGI diet. There were no significant differences between diets on major neonatal outcomes (birth weight and other anthropometric measures). The incidence of composite pregnancy complications was lower for the HPLGI than for the MPMGI diet (35.4% compared with 53.7%, respectively; P = 0.009), including cesarean delivery (15.4% compared with 28.8%, respectively; P = 0.03). There were no reported maternal, fetal, or neonatal deaths. Incidence of miscarriages (1%-2%) did not differ between groups. CONCLUSIONS: A moderate increase in dietary protein in conjunction with a reduction in glycemic index during the last 2 trimesters of pregnancy reduced GWG and limited complications and cesarean deliveries among women with overweight or obesity.

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Type 1 diabetes is an immune-driven disease, where the insulin-producing beta cells from the pancreatic islets of Langerhans becomes target of immune-mediated destruction. Several studies have highlighted the implication of circulating and exosomal microRNAs (miRNAs) in type 1 diabetes, underlining its biomarker value and novel therapeutic potential. Recently, we discovered that exosome-enriched extracellular vesicles carry altered levels of both known and novel miRNAs in breast milk from lactating mothers with type 1 diabetes. In this study, we aimed to characterize exosomal miRNAs in the circulation of lactating mothers with and without type 1 diabetes, hypothesizing that differences in type 1 diabetes risk in offspring from these groups are reflected in the circulating miRNA profile. We performed small RNA sequencing on exosome-enriched extracellular vesicles extracted from plasma of 52 lactating mothers around 5 weeks postpartum (26 with type 1 diabetes and 26 age-matched controls), and found a total of 2,289 miRNAs in vesicles from type 1 diabetes and control libraries. Of these, 176 were differentially expressed in plasma from mothers with type 1 diabetes (167 upregulated; 9 downregulated, using a cut-off of abs(log2FC) >1 and FDR adjusted p-value <0.05). Extracellular vesicles were verified by nanoparticle tracking analysis, transmission electron microscopy and immunoblotting. Five candidate miRNAs were selected based on their involvement in diabetes and immune modulation/beta-cell functions: hsa-miR-127-3p, hsa-miR-146a-5p, hsa-miR-26a-5p, hsa-miR-24-3p and hsa-miR-30d-5p. Real-time qPCR validation confirmed that hsa-miR-146a-5p, hsa-miR-26a-5p, hsa-miR-24-3p, and hsa-miR-30d-5p were significantly upregulated in lactating mothers with type 1 diabetes as compared to lactating healthy mothers. To determine possible target genes and affected pathways of the 5 miRNA candidates, computational network-based analyses were carried out with TargetScan, mirTarBase, QIAGEN Ingenuity Pathway Analysis and PantherDB database. The candidates showed significant association with inflammatory response and cytokine and chemokine mediated signaling pathways. With this study, we detect aberrant levels of miRNAs within plasma extracellular vesicles from lactating mothers with type 1 diabetes during the postpartum period, including miRNAs with associations to disease pathogenesis and inflammatory responses.

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Prior gestational diabetes mellitus (pGDM) is associated with increased risk of nonalcoholic fatty liver disease (NAFLD). Treatment with glucagon-like peptide 1 (GLP-1) receptor agonists has shown beneficial effects in NAFLD patients. We evaluated the effect of the GLP-1 analogue liraglutide on NAFLD features in women with pGDM. Eighty-two overweight/obese, nondiabetic women with pGDM were included. We performed abdominal ultrasound, transient elastography with controlled attenuation parameter (CAP), and blood sampling at baseline and after 1 year. Thirty-seven women were randomized to liraglutide (1.8 mg once-daily) and 45 to placebo. Based on the ultrasound scan, 18 women (22%) had ultrasound-verified NAFLD at baseline and of these, 10 (56%) received liraglutide treatment. After 1 year, eight participants no longer had steatosis, four in each treatment group. The number of participants who developed NAFLD was similar in the two treatment groups; five in the liraglutide group and six in the placebo group (p = 0.74). Compared to placebo, liraglutide reduced the CAP-assessed intrahepatic fat content (-28 (-44;-11) vs. 2 (-13;18) dB/m, p < 0.01) and body weight (-4.7 (-6.4;-2.9) vs. -1.4 (-3;0.3) kg, p < 0.01). One-year's liraglutide treatment had no effect on the presence of ultrasound-diagnosed NAFLD in overweight/obese nondiabetic women with pGDM, but reduced body weight and steatosis assessed by transient elastography with CAP.

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The breast milk plays a crucial role in shaping the initial intestinal microbiota and mucosal immunity of the infant. Interestingly, breastfeeding has proven to be protective against the early onset of immune-mediated diseases including type 1 diabetes. Studies have shown that exosomes from human breast milk are enriched in immune-modulating miRNAs suggesting that exosomal miRNAs (exomiRs) transferred to the infant could play a critical role in the development of the infant's immune system. We extracted exomiRs from breast milk of 52 lactating mothers (26 mothers with type 1 diabetes and 26 healthy mothers), to identify any differences in the exomiR content between the two groups. Small RNA-sequencing was performed to identify known and novel miRNAs in both groups. A total of 631 exomiRs were detected by small RNA sequencing including immune-related miRNAs such as hsa-let-7c, hsa-miR-21, hsa-miR-34a, hsa-miR-146b, and hsa-miR-200b. In addition, ~200 novel miRNAs were identified in both type 1 diabetes and control samples. Among the known miRNAs, nine exomiR's were found differentially expressed in mothers with type 1 diabetes compared to healthy mothers. The highly up-regulated miRNAs, hsa-miR-4497, and hsa-miR-3178, increased lipopolysaccharide-induced expression and secretion of tumor necrosis factor α (TNFα) in human monocytes. The up-regulated miRNA target genes were significantly enriched for longevity-regulating pathways and FoxO signaling. Our findings suggest a role of breast milk-derived exomiRs in modulating the infant's immune system.

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PURPOSE: To describe the association between quantity of blood loss, duration of the third stage of labour, retained placenta and other risk factors, and to describe the role of a retained placenta depending on the cutoff used to define postpartum haemorrhage. METHODS: Cohort study of all vaginal deliveries at two Danish maternity units between 1 January 2009 and 31 December 2013 (n = 43,357), univariate and multivariate linear regression statistical analyses. RESULTS: A retained placenta was shown to be a strong predictor of quantity of blood loss and duration of the third stage of labour a weak predictor of quantity of blood loss. The predictive power of the third stage of labour was further reduced in the multivariate analysis when including retained placenta in the model. There was an increase in the role of a retained placenta depending on the cutoff used to define postpartum haemorrhage, increasing from 12% in cases of blood loss ≥ 500 ml to 53% in cases of blood loss ≥ 2000 ml CONCLUSION: The predictive power of duration of the third stage of labour in regard to postpartum blood loss was diminished by the influence of a retained placenta. A retained placenta was, furthermore, present in the majority of most severe cases.

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AIMS/HYPOTHESIS: We investigated whether a reduced incretin effect, as observed in patients with type 2 diabetes, can be detected in high-risk individuals, such as women with prior gestational diabetes mellitus (pGDM). METHODS: In this cross-sectional study, 102 women without diabetes with pGDM and 15 control participants without pGDM and with normal glucose tolerance (NGT) underwent a 4 h 75 g OGTT and an isoglycaemic i.v. glucose infusion (IIGI). Women with pGDM were classified as having NGT or prediabetes (impaired fasting glucose and/or impaired glucose tolerance). Insulin sensitivity was assessed using the Matsuda index and HOMA2-IR and the incretin effect was calculated from insulin responses during the study (100% × [AUCinsulin,OGTT - AUCinsulin,IIGI]/AUCinsulin,OGTT). RESULTS: Sixty-three of the 102 women with pGDM (62%) had prediabetes (median [interquartile range]: age, 38.3 [6.5] years; BMI, 32.1 [5.8] kg/m2) and 39 women (38%) had NGT (age, 39.5 [5.6] years; BMI, 31.0 [6.7] kg/m2). Control participants (n = 15) were not significantly different from the pGDM group with regards to age (39.2 [7.4] years) and BMI (28.8 [9.2] kg/m2). Compared with women with NGT and control participants, women with prediabetes had lower insulin sensitivity, as measured by the Matsuda index (3.0 [2.4] vs 5.0 [2.6] vs 1.5 [1.8], respectively; p < 0.001). The incretin effect was 55.3% [27.8], 73.8% [19.0] and 76.7% [24.6] in women with prediabetes, women with normal glucose tolerance and control participants, respectively (p < 0.01). CONCLUSION/INTERPRETATION: Prediabetes was highly prevalent in women with pGDM, and alterations in the incretin effect were detected in this group before the development of type 2 diabetes. TRIAL REGISTRATION: clinicaltrialsregister.eu 2012-001371-37-DK.

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OBJECTIVE: The aim of the present study was to describe the risk of internal herniation (IH) and the obstetric outcome in pregnant women with Roux-en-Y gastric bypass (RYGB) and episodes of upper abdominal pain. METHODS: The cohort included 133 women with RYGB: 94 with 113 pregnancies, from the local area referred for routine antenatal care (local cohort) and 39 with 40 pregnancies referred from other hospitals for specialist consultation due to RYGB. RYGB was mainly performed without closure of the mesenteric defects. Data collected from medical records were episodes of upper abdominal pain, pregestational and gestational abdominal surgery and pregnancy outcome. The risk of upper abdominal pain was estimated in the local cohort. Surgical intervention, IH and obstetric outcome according to pain were evaluated for 139 pregnancies with delivery of a singleton after 24 weeks of gestation (birth cohort). RESULTS: Upper abdominal pain complicated 42/113 (37.2 %) pregnancies in the local cohort and 11 women (9.7 %) had IH. In the birth cohort, upper abdominal pain complicated 64/139 (46.0 %) pregnancies; surgery was performed in 30/64 (46.9 %), and IH diagnosed in 21/64 (32.8 %). The median gestational age at onset of pain was 25 + 3 weeks. Women reporting abdominal pain had a higher risk of preterm birth (n = 14/64 vs. 1/75, p < 0.005), lower median gestational length (269 vs. 278 days, p < 0.005) and lower median birth weight (3018 vs. 3281 g, p = 0.002) compared to women without abdominal pain. CONCLUSIONS: Upper abdominal pain during pregnancy is frequent among women with Roux-en-Y gastric bypass, is often due to IH and is associated with adverse pregnancy outcome.

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OBJECTIVE: Type 2 diabetes increases the risk of nonalcoholic fatty liver disease (NAFLD), which is a potentially reversible condition but is also associated with progressive fibrosis and cirrhosis. Women with prior gestational diabetes mellitus (pGDM) have a higher risk for NAFLD. RESEARCH DESIGN AND METHODS: One hundred women without diabetes who had pGDM (median [interquartile range]: age 38.6 [6.4] years; BMI 31.0 [6.2] kg/m2) and 11 healthy control subjects without NAFLD (age 37.9 [7.8] years; BMI 28.1 [0.8] kg/m2) underwent a 75-g oral glucose tolerance test (OGTT), DXA whole-body scan, and ultrasonic evaluation of hepatic steatosis. RESULTS: Twenty-four (24%) women with pGDM had NAFLD on the basis of the ultrasound scan. None had cirrhosis. Women with NAFLD had a higher BMI (P = 0.0002) and waist circumference (P = 0.0003), increased insulin resistance (P = 0.0004), and delayed suppression of glucagon after the OGTT (P < 0.0001), but NAFLD was not associated with the degree of glucose intolerance (P = 0.2196). Visceral fat mass differed among the three groups, with the NAFLD group having the highest amount of fat and the control subjects the lowest (P = 0.0003). By logistic regression analysis, insulin resistance (P = 0.0057) and waist circumference (P = 0.0109) were independently associated with NAFLD. CONCLUSIONS: NAFLD was prevalent in this cohort of relatively young and nonseverely obese women with pGDM who are considered healthy apart from their increased risk for diabetes. Insulin resistance and a larger waist circumference were independently associated with the presence of NAFLD, whereas glucose intolerance was not.

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INTRODUCTION: Bacterial vaginosis (BV) is characterized by a dysbiosis of the vaginal microbiota with a depletion of Lactobacillus spp. In pregnancy, prevalence's between 7 and 30% have been reported depending on the study population and the definition. BV may be associated with an increased risk of spontaneous preterm delivery (sPTD). However, it is controversial whether or not BV-positive pregnant women will benefit from treatment to reduce the risk of sPTD. We could not identify any good-quality guideline addressing this issue. Consequently we aimed to produce this clinical recommendation based on GRADE. MATERIAL AND METHODS: Systematic literature searches were conducted in the following databases: Guidelines International Network: G-I-N, Medline, Embase, The Cochrane Database of Systematic Reviews, Web of Science and http://www.clinicaltrials.gov from 1999 to 3 October 2014. Hence, nine guidelines, 34 reviews, 18 randomized controlled trials and 12 observational studies were included. RESULTS: The GRADE quality of evidence was consistently low or very low, primarily because none of the risk ratios (RR) for the risk of sPTD at <37 weeks were statistically significant. Concerning treatment with metronidazole, RR was 1.11 (95% CI 0.93-1.34) in low-risk pregnancies and 0.96 (95% CI 0.78-1.18) in high risk pregnancies. Concerning treatment with clindamycin at any gestational age, the RR was 0.87 (95% CI 0.73-1.05). CONCLUSION: This systematic review gives a strong recommendation against treatment with metronidazole and a weak recommendation against treatment with clindamycin to reduce the sPTD rate in both high-risk and low-risk pregnancies with BV.

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Perimortem caesarean section can be decisive for the outcome of a cardiac arrest in pregnancy for both mother and fetus. We describe a case story of the management of cardiac arrest in early labour where perimortem caesarean section proved to be life-saving for both mother and child. The child was delivered alive seven minutes after recorded cardiac arrest, and the mother had return of spontaneous circulation one minute after delivery. The mother recovered well with no serious sequelae to the resuscitation. We discuss the importance of timely decision and execution of perimortem caesarean.

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INTRODUCTION: The aim of the study was to examine the prevalence of anal incontinence (AI) during pregnancy and 1 year after delivery in primiparous women and to compare it with the prevalences in nulliparous women. MATERIAL AND METHODS: A validated questionnaire regarding AI was filled in by 1018 primiparous women after delivery and by 1836 nulliparous women (baseline). A similar questionnaire was filled in 1 year later by both groups. RESULTS: At baseline the prevalence of flatus incontinence was significantly higher in the primiparous than the nulliparous women (35 vs. 25%), while incontinence for liquid stools was significantly less frequent (8 vs. 20%). Prevalences of incontinence for solid stools were similar. One year later the prevalence of AI was similar in the two groups (flatus incontinence 24 vs. 25%, incontinence for liquid stools 18 vs. 19% and incontinence for solid stools 4 vs. 3%). AI 1 year after the delivery was not related to the mode of delivery. Women with grade 3 or 4 perineal lesions had a significantly higher prevalence of flatus incontinence 1 year after the delivery compared with women without such lesions (48 vs. 23%, p = 0.00). CONCLUSIONS: This prospective cohort study showed remarkably high prevalences of AI during pregnancy and 1 year after delivery in primiparous women and likewise in nulliparous women at baseline and 1 year later. These results may indicate that factors other than pregnancy and delivery are of importance for AI in young women.

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OBJECTIVE: The aim of the study is to explore the impact of time between Roux-en-Y gastric bypass (RYGB) and pregnancy on obstetrical outcome and nutritional derangements. METHODS: In a retrospective cross-sectional study of pregnant women admitted for antenatal care at two tertiary hospitals, we examined 153 women with RYGB and a singleton pregnancy of at least 24 weeks. The women were stratified according to a pregnancy <18 months (40 women) or ≥18 months (113 women) after RYGB. Main outcome measures were nutritional parameters and glycated haemoglobin 1Ac (HbA1c) in second and third trimester of pregnancy, gestational hypertension, length of pregnancy, mode of delivery and foetal birth weight. RESULTS: The two groups were comparable regarding age, parity and prepregnancy body mass index. The frequency of iron deficiency anaemia (ferritin <12 µg/L and haemoglobin <6.5 mmol/L/10.5 g/dL) was significantly higher in the late group, 29 vs. 8 % in the early group, p = 0.010. No differences were found for vitamin B12, vitamin D and zinc. Median HbA1c was significantly higher in the late group than in the early group (33 vs. 31 mmol/mol, p = 0.027). There were no significant differences in the risk of adverse pregnancy outcome or birth weight between the two groups. CONCLUSION: A long surgery-to-pregnancy time interval after a RYGB increases the risk of iron deficiency anaemia but not of other nutritional deficits. Time interval does not seem to have an adverse effect on the obstetrical outcome, including intrauterine growth restriction. Specific attention is needed on iron deficit with increasing surgery-to-pregnancy time interval.

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INTRODUCTION AND HYPOTHESIS: The objective was to examine the relationship between maternal and perinatal factors and the occurrence of stress (SUI) or mixed (MUI) urinary incontinence (UI) 1 year after the first vaginal delivery in primiparous women. METHODS: Participants in this prospective cohort were recruited consecutively from June 2003 to July 2005 from all eligible women who delivered in the department. A validated questionnaire, the International Consultation of Incontinence Questionnaire Short Form (ICIQ-SF) was completed by all participants 2-3 days after delivery, and a similar second questionnaire was filled out 1 year later. Additional data were obtained from the medical records. The first questionnaire was completed by 1,018 women (63 %) and the second by 859 women (84 %). The study group comprised the 575 women without any UI before the pregnancy and who had a vaginal delivery. The primary analysis comprised 117 women with either SUI or MUI 1 year after the vaginal delivery and 403 women without any UI. RESULTS: In univariate analyses, the following factors were associated with SUI or MUI: prepregnancy body mass index (BMI) ≥ 30 (p < 0.05), UI during the pregnancy (p < 0.05), perineal lesions (p < 0.05), and anal sphincter tears (p = 0.05). Logistic regression analysis showed that SUI or MUI was strongly associated with UI during the pregnancy [adjusted odds ratio (OR) 4.7, 95 % confidence interval (CI) 2.9-7.7) and inversely associated with oxytocin augmentation (adjusted OR 0.5, 95 % CI 0.3-0.9). CONCLUSIONS: SUI or MUI 1 year after the first vaginal delivery was strongly associated with UI during the pregnancy and inversely associated with oxytocin augmentation.

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INTRODUCTION: Pregnancy is associated with decreased insulin sensitivity, which is usually overcome by a compensatory increase in insulin secretion. Some pregnant women are not able to increase their insulin secretion sufficiently, and consequently develop gestational diabetes mellitus (GDM). The disease normally disappears after delivery. Nevertheless, women with previous GDM have a high risk of developing type 2 diabetes (T2D) later in life. We aim to investigate the early development of T2D in women with previous GDM and to evaluate whether treatment with the glucagon-like peptide-1 receptor (GLP-1R) agonist, liraglutide, may modify their risk of developing T2D. METHODS AND ANALYSES: 100 women with previous GDM will be randomised to either liraglutide or placebo treatment for 1 year (blinded) with an open-label extension for another 4 years. Additionally, 15 women without previous GDM will constitute a baseline control group. Women will be tested with an oral glucose tolerance test (primary endpoint: area under the curve for plasma glucose) and an isoglycaemic intravenous glucose infusion at baseline, after 1 year and after 5 years. Additional evaluations include a glucagon test, dual-energy X-ray absorptiometry, imaging of the liver (ultrasound elastography and fibroscanning), an ad libitum meal for food intake evaluation and questionnaires related to appetite, quality of life and alcohol consumption habits. ETHICS AND DISSEMINATION: The protocol has been approved by the Danish Medicines Agency, the Scientific-Ethical Committee of the Capital Region of Denmark, and the Danish Data Protection Agency and will be carried out under the surveillance and guidance of the GCP unit at Copenhagen University Hospital Bispebjerg in compliance with the ICH-GCP guidelines and in accordance with the Helsinki Declaration. Positive, negative and inconclusive results will be published at scientific conferences and as one or more scientific manuscripts in peer-reviewed journals. REGISTRATIONS: The trial is registered at https://eudract.ema.europa.eu (2012-001371-37) and http://www.clinicaltrials.gov (NCT01795248).

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BACKGROUND: Postpartum haemorrhage (PPH) remains a leading cause of maternal mortality worldwide. In Denmark 2% of parturients receive blood transfusion. During the course of bleeding fibrinogen (coagulation factor I) may be depleted and fall to critically low levels, impairing haemostasis and thus worsening the ongoing bleeding. A plasma level of fibrinogen below 2 g/L in the early phase of postpartum haemorrhage is associated with subsequent development of severe haemorrhage. Use of fibrinogen concentrate allows high-dose substitution without the need for blood type crossmatch. So far no publications of randomised controlled trials involving acutely bleeding patients in the obstetrical setting have been published. This trial aims to investigate if early treatment with fibrinogen concentrate reduces the need for blood transfusion in women suffering severe PPH. METHODS/DESIGN: In this randomised placebo-controlled double-blind multicentre trial, parturients with primary PPH are eligible following vaginal delivery in case of: manual removal of placenta (blood loss ≥ 500 ml) or manual exploration of the uterus after the birth of placenta (blood loss ≥ 1000 ml). Caesarean sections are also eligible in case of perioperative blood loss ≥ 1000 ml. The exclusion criteria are known inherited haemostatic deficiencies, prepartum treatment with antithrombotics, pre-pregnancy weight <45 kg or refusal to receive blood transfusion. Following informed consent, patients are randomly allocated to either early treatment with 2 g fibrinogen concentrate or 100 ml isotonic saline (placebo). Haemostatic monitoring with standard laboratory coagulation tests and thromboelastography (TEG, functional fibrinogen and Rapid TEG) is performed during the initial 24 hours.Primary outcome is the need for blood transfusion. To investigate a 33% reduction in the need for blood transfusion, a total of 245 patients will be included. Four university-affiliated public tertiary care hospitals will include patients during a two-year period. Adverse events including thrombosis are assessed in accordance with International Conference on Harmonisation (ICH) good clinical practice (GCP). DISCUSSION: A widespread belief in the benefits of early fibrinogen substitution in cases of PPH has led to increased off-label use. The FIB-PPH trial is investigator-initiated and aims to provide an evidence-based platform for the recommendations of the early use of fibrinogen concentrate in PPH. TRIAL REGISTRATION: ClincialTrials.gov NCT01359878.

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AIMS: To investigate the impact of the first pregnancy and delivery on the prevalence and types of urinary incontinence during pregnancy and 1 year after delivery. METHODS: The study was a prospective cohort study with a control group. Primiparous women, who delivered in our department from June 2003 to July 2005, participated. The women filled out a questionnaire 2-3 days after the delivery and a new questionnaire after 1 year. The questionnaires comprised basic characteristics and symptoms of urinary incontinence. An attempted age-matched control group of nulliparous women was included, and filled out similar questionnaires. Prevalences and types of urinary incontinence, and a combined severity- and bother-score (ICIQ-SF score) among the incontinent women, were calculated and compared. RESULTS: The two groups differed significantly in age and most basic characteristics. During pregnancy, the prevalence of any type of urinary incontinence in the primiparous group was 32.1%, compared to 13.8% in the control group. Adjusted OR = 3.3 (95%CI = 2.4-4.4). One year after delivery, the prevalence in the primiparous group was 29.3%, compared to 16.6% in the control group. Adjusted OR = 2.5 (95%CI = 1.8-3.5). ICIQ-SF mean scores among the incontinent women varied insignificantly between 5.8 and 6.2. CONCLUSIONS: The prevalence of urinary incontinence during pregnancy was 3.3 times higher compared with a control group of nulliparous women. After 1 year, the difference was reduced, but still 2.5 times higher in the primiparous group. The symptoms and impact on quality of life seemed to be mild to moderate in both groups.

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