Hemoglobin A1c Trajectories During Pregnancy and Adverse Outcomes in Women With Type 2 Diabetes: A Danish National Population-Based Cohort Study.

OBJECTIVE: To identify and characterize groups of pregnant women with type 2 diabetes with distinct hemoglobin A1c (HbA1c) trajectories across gestation and to examine the association with adverse obstetric and perinatal outcomes. RESEARCH DESIGN AND METHODS: This was a retrospective Danish national cohort study including all singleton pregnancies in women with type 2 diabetes, giving birth to a liveborn infant, between 2004 and 2019. HbA1c trajectories were identified using latent class linear mixed-model analysis. Associations with adverse outcomes were examined with logistic regression models. RESULTS: A total of 1,129 pregnancies were included. Three HbA1c trajectory groups were identified and named according to the glycemic control in early pregnancy (good, 59%; moderate, 32%; and poor, 9%). According to the model, all groups attained an estimated HbA1c <6.5% (48 mmol/mol) during pregnancy, with no differences between groups in the 3rd trimester. Women with poor glycemic control in early pregnancy had lower odds of having an infant with large for gestational age (LGA) birth weight (adjusted odds ratio [aOR] 0.57, 95% CI 0.40-0.83), and higher odds of having an infant with small for gestational age (SGA) birth weight (aOR 2.49, 95% CI 2.00-3.10) and congenital malformation (CM) (aOR 4.60 95% CI 3.39-6.26) compared with women with good glycemic control. There was no evidence of a difference in odds of preeclampsia, preterm birth, and caesarean section between groups. CONCLUSIONS: Women with poor glycemic control in early pregnancy have lower odds of having an infant with LGA birth weight, but higher odds of having an infant with SGA birth weight and CM.

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.

Danish Diabetes Birth Registry 2: a study protocol of a national prospective cohort study to monitor outcomes of pregnancies of women with pre-existing diabetes.

INTRODUCTION: Despite technological developments and intensified care, pregnancies in women with pre-existing diabetes are still considered high-risk pregnancies. The rate of adverse outcomes in pregnancies affected by diabetes in Denmark is currently unknown, and there is a limited understanding of mechanisms contributing to this elevated risk. To address these gaps, the Danish Diabetes Birth Registry 2 (DDBR2) was established. The aims of this registry are to evaluate maternal and fetal-neonatal outcomes based on 5 years cohort data, and to identify pathophysiology and risk factors associated with short-term and long-term outcomes of pregnancies in women with pre-existing diabetes. METHODS AND ANALYSIS: The DDBR2 registry is a nationwide 5-year prospective cohort with an inclusion period from February 2023 to February 2028 of pregnancies in women with all types of pre-existing diabetes and includes registry, clinical and questionnaire data and biological samples of mother-partner-child trios. Eligible families (parents age ≥18 years and sufficient proficiency in Danish or English) can participate by either (1) basic level data obtained from medical records (mother and child) and questionnaires (partner) or (2) basic level data and additional data which includes questionnaires (mother and partner) and blood samples (all). The primary maternal outcome is Hemoglobin A1c (HbA1c) levels at the end of pregnancy and the primary offspring endpoint is the birth weight SD score. The DDBR2 registry will be complemented by genetic, epigenetic and metabolomic data as well as a biobank for future research, and the cohort will be followed through data from national databases to illuminate possible mechanisms that link maternal diabetes and other parental factors to a possible increased risk of adverse long-term child outcomes. ETHICS AND DISSEMINATION: Approval from the Ethical Committee is obtained (S-20220039). Findings will be sought published in international scientific journals and shared among the participating hospitals and policymakers. TRIAL REGISTRATION NUMBER: NCT05678543.

Infant Ustekinumab Clearance, Risk of Infection, and Development After Exposure During Pregnancy.

BACKGROUND: Evidence on ustekinumab safety in pregnancy is gradually expanding, but its clearance in the postnatal period is unknown. The aim of this study was to investigate ustekinumab concentrations in umbilical cord blood and rates of clearance after birth, as well as how these correlate with maternal drug concentrations, risk of infection, and developmental milestones during the first year of life. METHODS: Pregnant women with inflammatory bowel disease were prospectively recruited from 19 hospitals in Denmark and the Netherlands between 2018 and 2022. Infant infections leading to hospitalization/antibiotics and developmental milestones were assessed. Serum ustekinumab concentrations were measured at delivery and specific time points. Nonlinear regression analysis was applied to estimate clearance. RESULTS: In 78 live-born infants from 76 pregnancies, we observed a low risk of adverse pregnancy outcomes and normal developmental milestones. At birth, the median infant-mother ustekinumab ratio was 2.18 (95% confidence interval, 1.69-2.81). Mean time to infant clearance was 6.7 months (95% confidence interval, 6.1-7.3 months). One in 4 infants at 6 months had an extremely low median concentration of 0.015 µg/mL (range 0.005-0.12 µg/mL). No variation in median ustekinumab concentration was noted between infants with (2.8 [range 0.4-6.9] µg/mL) and without (3.1 [range 0.7-11.0] µg/mL) infections during the first year of life (P = .41). CONCLUSIONS: No adverse signals after intrauterine exposure to ustekinumab were observed with respect to pregnancy outcome, infections, or developmental milestones during the first year of life. Infant ustekinumab concentration was not associated with risk of infections. With the ustekinumab clearance profile, live attenuated vaccination from 6 months of age seems of low risk.

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.

Full-term induction of labor vs expectant management and cesarean delivery in women with obesity: systematic review and meta-analysis.

OBJECTIVE: This study aimed to review the literature comparing full-term induction of labor with expectant management in women with obesity on the risk of cesarean delivery and other adverse outcomes. DATA SOURCES: A literature search was performed on PubMed, EMBASE, Scopus, ClinicalTrials.gov, and the Cochrane Library. This study had no time, language, or geographic restriction. STUDY ELIGIBILITY CRITERIA: Studies were eligible if (1) they were cohort or randomized controlled trials, (2) they compared induction of labor at early or late term with expectant management, and (3) they included women with a body mass index of ≥30 kg/m2. Studies restricted to women with multiple pregnancy, premature rupture of membranes, or noncephalic presentation were excluded. The primary outcome was cesarean delivery. The secondary outcomes included maternal and neonatal mortality and morbidities and were evaluated. METHODS: The risk of bias was assessed by 2 authors using the Risk of Bias In Non-Randomized Studies of Interventions tool. Only studies assessed with low or moderate risk of bias contributed to the meta-analysis. Data were combined to pooled relative risks and 95% confidence intervals using random effects models. The quality of evidence was assessed for selected outcomes. RESULTS: Of the 232 studies identified, 13 were aligned with the inclusion criteria, and 4 cohort studies, including 216,318 women with induction of labor and 1,122,769 women managed expectantly, were included in the meta-analysis for the primary outcome. In women with obesity, full-term induction of labor was associated with a lower risk of cesarean delivery than expectant management (19.7% vs 24.5%; relative risk, 0.71; 95% confidence interval, 0.63-0.81). Moreover, this study found the same direction of the association for other selected outcomes: severe perineal lacerations (relative risk, 0.65; 95% confidence interval, 0.48-0.89), maternal infection (relative risk, 0.42; 95% confidence interval, 0.21-0.84), perinatal mortality (relative risk, 0.41; 95% confidence interval, 0.18-0.90), low Apgar score (relative risk, 0.48; 95% confidence interval, 0.26-0.91), meconium aspiration syndrome (relative risk, 0.40; 95% confidence interval, 0.28-0.56), and macrosomia (relative risk, 0.57; 95% confidence interval, 0.43-0.75). Conversely, induction of labor was associated with an increased risk of instrumental vaginal delivery (relative risk, 1.12; 95% confidence interval, 1.02-1.22). The quality of evidence ranged from low to very low. CONCLUSION: Full-term induction of labor in women with obesity may reduce the risk of cesarean delivery compared with expectant management, but the quality of the evidence is low.

Mechanical Heart Valves, Pregnancy, and Bleeding: A Systematic Review and Meta-Analysis.

Anticoagulant therapy is essential in pregnant women with mechanical heart valves to prevent valve thrombosis. The risk of bleeding complications in these patients has not gained much attention. This systematic review and meta-analysis investigate the prevalence of bleeding peri-partum and post-partum in women with mechanical heart valves and also investigate whether bleeding risk differed across anticoagulant regimens or according to delivery mode. The present study was conducted according to The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Studies reporting bleeding prevalence in pregnant women with mechanical heart valves receiving anticoagulant therapy were identified through PubMed and Embase on December 08, 2021. Data on bleeding complications, delivery mode, and anticoagulation therapy were extracted. A total of 37 studies were included, reporting 423 bleeding complications in 2,508 pregnancies. A meta-analysis calculated a pooled prevalence of 0.13 (95% confidence interval [CI]: 0.09-0.18) bleeding episodes per pregnancy across anticoagulant regimens. The combination of unfractionated heparin (UFH) and vitamin K antagonist (VKA) and single VKA therapy showed the lowest risk of bleeding (8 and 12%). Unexpectedly, the highest risk of bleeding was found in women receiving a combination of low-molecular-weight-heparin (LMWH) and VKA (33%) or mono-therapy with LMWH (22%). However, this could be dose related. No difference in bleeding was found between caesarean section versus vaginal delivery (p = 0.08). In conclusion, bleeding episodes are common during pregnancy in women with mechanical heart valves receiving anticoagulant therapy. A combination of UFH and VKA or VKA monotherapy showed the lowest risk of bleeding.

Hyperglycemia in Pregnancy and Women's Health in the 21st Century.

Hyperglycemia is the commonest medical condition affecting pregnancy and its incidence is increasing globally in parallel with the twin epidemics of diabetes and obesity. Both pre-pregnancy diabetes and gestational diabetes are associated with short term pregnancy complications, with the risk of immediate complications generally broadly rising with more severe hyperglycemia. In this article we firstly consider these risks and their optimal management during pregnancy and then broaden our scope to consider the long-term implications of hyperglycemia in pregnancy as it relates to overall maternal and offspring health in a life course perspective.

Influence of maternal body mass index on human milk composition and associations to infant metabolism and gut colonisation: MAINHEALTH - a study protocol for an observational birth cohort.

INTRODUCTION: Human milk provides all macronutrients for growth, bioactive compounds, micro-organisms and immunological components, which potentially interacts with and primes infant growth and, development, immune responses and the gut microbiota of the new-born. Infants with an overweight mother are more likely to become overweight later in life and overweight has been related to the gut microbiome. Therefore, it is important to investigate the mother-milk-infant triad as a biological system and if the maternal weight status influences the human milk composition, infant metabolism and gut microbiome. METHODS AND ANALYSIS: This study aims to include 200 mother-infant dyads stratified into one of three body mass index (BMI) categories based on mother's prepregnancy BMI. Multiomics analyses include metabolomics, proteomics, glycomics and microbiomics methods, aiming to characterise human milk from the mothers and further relate the composition to infant gut microbiota and its metabolic impact in the infant. Infant gut microbiota is analysed using 16S sequencing of faeces samples. Nuclear magnetic resonance and mass spectrometry are used for the remaining omics analysis. We investigate whether maternal pre-pregnancy BMI results in a distinct human milk composition that potentially affects the initial priming of the infant's gut environment and metabolism early in life. ETHICS AND DISSEMINATION: The Central Denmark Region Committees on Health Research Ethics has approved the protocol (J-nr. 1-10-72-296-18). All participants have before inclusion signed informed consent and deputy informed consent in accordance with the Declaration of Helsinki II. Results will be disseminated to health professionals including paediatricians, research community, nutritional policymakers, industry and finally the public. The scientific community will be informed via peer-reviewed publications and presentations at scientific conferences, the industry will be invited for meetings, and the public will be informed via reports in science magazines and the general press. Data cleared for personal data, will be deposited at public data repositories. TRIAL REGISTRATION NUMBER: Danish regional committee of the Central Jutland Region, journal number: 1-10-72-296-18, version 6.Danish Data Protection Agency, journal number: 2016-051-000001, 1304. CLINICALTRIALS: gov, identifier: NCT05111990.

[Pregnancy after heart transplantation].

This is a case report of a 29-year-old woman who obtained pregnancy two and a half years after a heart transplant due to Danon syndrome. Pregnancy was planned and spontaneous. The fetus did not have Danon syndrome. At the frequent pregnancy visits, maternal echocardiography and fetal ultrasound examinations were reassuring. In gestational week 36+6, high blood pressure and subjective symptoms of severe pre-eclampsia occurred. A healthy boy (3,070 g) was born after an acute caesarean section. Blood pressure normalized rapidly, and the family was discharged on day four after delivery.

[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.

Induction of labour at 39 weeks versus expectant management in low-risk obese women: study protocol for a randomised controlled study.

INTRODUCTION: Obesity is associated with many pregnancy complications, including both fetal macrosomia and prolonged labour. As a result, there is often also an increased risk of caesarean section. In other settings, labour induction near to term reduces adverse outcomes such as stillbirth and birth injury, without causing more caesarean deliveries. It has been suggested that induction will reduce adverse events in this setting too, but there have been no trials and the effect on caesarean section is unknown. The objective of this study is to compare induction of labour in gestational week 39 with expectant management on the risk of caesarean section in women with body mass index ≥30 kg/m2. METHODS AND ANALYSIS: An open label randomised controlled multicentre trial are conducted at Danish delivery departments with an in-house neonatal intensive care unit. Recruitment started October 2020. A total of 1900 women with a prepregnancy body mass index ≥30 kg/m2 are randomised in a 1:1 ratio to either labour induction at 39 weeks and 0 to 3 days of gestation or to expectant management; that is, waiting for spontaneous labour onset or induction if medically indicated. The primary outcome is caesarean section. Data will be analysed according to intention-to-treat. ETHICS AND DISSEMINATION: The Central Denmark Region Committee on Biomedical Research Ethics approved the study. The study is conducted in accordance with the ethical principles outlined in the latest version of the 'Declaration of Helsinki' and the 'Guideline for Good Clinical Practice' related to experiments on humans. The trial findings will be disseminated to participants, clinicians, commissioning groups and via peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04603859.

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.

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

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: This study aimed to investigate the effect of 20 minutes of postprandial interval walking on glycemic control and glycemic variability in pregnant women diagnosed as having gestational diabetes mellitus. STUDY DESIGN: A crossover controlled trial including 14 pregnant women (gestational age 31.8±1.3 weeks) diagnosed as having gestational diabetes mellitus (75 g oral glucose load with 2-hour venous plasma glucose of ≥9.0 mmol/L) was conducted. Participants completed a 4-day intervention period and a 4-day control period with 3 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 3 minutes of 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: Of note, 20 minutes of postprandial interval walking significantly reduced glycemic control during daytime hours relative to the control period (4-day mean glucose, 5.31 [5.04-5.59] vs 5.53 [5.25-5.81] mmol/L [95.6 (90.7-100.6) vs 99.5 (94.5-104.6) mg/dL]; P<.05). On each individual trial day, interval walking significantly reduced glycemic control during daytime hours on day 1 (mean glucose, 5.19 [4.92-5.47] vs 5.55 [5.27-5.83] mmol/L [93.4 (88.6-98.5) vs 99.9 (94.9-104.9) mg/dL]; P=.00), day 2 (mean glucose, 5.32 [5.05-5.60] vs 5.57 [5.29-5.84] mmol/L [95.8 (90.9-100.8) vs 100.3 (95.2-105.1) mg/dL]; P=.00), and day 3 (mean glucose, 5.27 [5.00-5.54] vs 5.46 [5.19-5.74] mmol/L [94.9 (90.0-99.7) vs 98.3 (93.4-103.3) mg/dL]; P=.00), but not on day 4. CONCLUSION: A total of 20 minutes of postprandial interval walking seems to be an effective way to control postprandial glucose excursions in women with gestational diabetes mellitus.

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.

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

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.

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.

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

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 HbA1c 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.