Prophylactic progesterone and preterm birth.

This review summarises the present knowledge of prophylactic progesterone and preterm birth. Preterm birth (less-than 37 weeks) is a leading cause of neonatal mortality and morbidity worldwide. The incidence varies globally but remains low in the Nordic countries (5-6%). Prediction and prevention are complicated due to diverse aetiology, but obstetric history and cervical length can improve prediction. Prophylactic vaginal progesterone initiated between 12 and 24 weeks of gestation is recommended to reduce preterm birth less-than 33-35 weeks in singleton pregnancies with a history of preterm birth or with a short cervix (less-than 25 mm) and can be considered for twin pregnancies with the same risk factors.

Characterization of genetic variants of GIPR reveals a contribution of ß-arrestin to metabolic phenotypes.

Incretin-based therapies are highly successful in combatting obesity and type 2 diabetes1. Yet both activation and inhibition of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in combination with glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) activation have resulted in similar clinical outcomes, as demonstrated by the GIPR-GLP-1R co-agonist tirzepatide2 and AMG-133 (ref. 3) combining GIPR antagonism with GLP-1R agonism. This underlines the importance of a better understanding of the GIP system. Here we show the necessity of ß-arrestin recruitment for GIPR function, by combining in vitro pharmacological characterization of 47 GIPR variants with burden testing of clinical phenotypes and in vivo studies. Burden testing of variants with distinct ligand-binding capacity, Gs activation (cyclic adenosine monophosphate production) and ß-arrestin 2 recruitment and internalization shows that unlike variants solely impaired in Gs signalling, variants impaired in both Gs and ß-arrestin 2 recruitment contribute to lower adiposity-related traits. Endosomal Gs-mediated signalling of the variants shows a ß-arrestin dependency and genetic ablation of ß-arrestin 2 impairs cyclic adenosine monophosphate production and decreases GIP efficacy on glucose control in male mice. This study highlights a crucial impact of ß-arrestins in regulating GIPR signalling and overall preservation of biological activity that may facilitate new developments in therapeutic targeting of the GIPR system.

Socioeconomic, lifestyle and biological determinants of cervical screening coverage: Lolland-Falster Health Study, Denmark.

BACKGROUND: Cervical cancer is preventable. Screening is important for early detection. However, even in high-income countries, coverage is sub-optimal. We identified socioeconomic, lifestyle and biological determinants of cervical screening coverage. METHODS: In Denmark, women aged 23-64 are free of charge personally invited to screening. All cervical cell samples are registered centrally in the Patobank. We linked data from the Lolland-Falster Health Study (LOFUS) with Patobank data. LOFUS was a population-based health survey undertaken in 2016-2020. With logistic regression, coverage defined as ≥1 cervical sample registered within a 6-year period from 2015 to 2020 was compared across levels of risk factors expressed as adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS: Among 13 406 women of screening aged 23-64 and invited to LOFUS, 72% had ≥1 cervical sample registered. Non-participation in LOFUS was a strong predictor of low coverage; aOR 0.32; 95% CI 0.31-0.36. Among LOFUS participants, education was a strong predictor of coverage in univariate analysis, OR 0.58; 95% CI 0.48-0.71, but this association disappeared in multi-variate analysis, aOR 0.86; 95% CI 0.66-1.10. In multi-variate analysis, predictors of low coverage were high age, living without a partner, retired, current smoker, poor self-rated health, elevated blood pressure and elevated glycated haemoglobin. CONCLUSIONS: Women with low cervical screening coverage had limited contact to healthcare, exemplified by non-participation in LOFUS, and pertinent health and social problems, exemplified by elevated blood pressure and glycated haemoglobin, poor self-rated health, and retirement already in screening age. Structural changes in screening are needed to reach non-screened women.

Long-Term Follow-Up on Morbidity Among Women With a History of Gestational Diabetes Mellitus: A Systematic Review.

BACKGROUND: Gestational diabetes mellitus (GDM) complicates up to 10% of pregnancies and is a well-known risk factor for type 2 diabetes mellitus (T2DM) and cardiovascular disease. Little is known about possible long-term risks of other diseases. BACKGROUND: The aim was to review the literature for evidence of associations with morbidity other than T2DM and cardiovascular disease and with long-term mortality. METHODS: A systematic review based on searches in Medline, Embase, and Cochrane Library until March 31, 2021, using a broad range of keywords. We extracted study characteristics and results on associations between GDM and disease occurrence at least 10 years postpartum, excluding studies on women with diabetes prior to pregnancy or only diabetes prior to outcome. The results are reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Newcastle-Ottawa Scale was used to assess risk of bias. RESULTS: We screened 3084 titles, 81 articles were assessed full-text, and 15 included in the review. The strongest evidence for an association was for kidney diseases, particularly in Black women. We found indication of an association with liver disease, possibly restricted to women with T2DM postpartum. The association between GDM and breast cancer had been studied extensively, but in most cases based on self-reported diagnosis and with conflicting results. Only sparse and inconsistent results were found for other cancers. No study on thyroid diseases was found, and no study reported on short-term or long-term mortality in women with a history of GDM. CONCLUSION: Given the frequency of GDM, there is a need for better evidence on possible long-term health consequences, in particular, studies based on comprehensive records of diagnosis of GDM and long-term health outcomes.

Newborn body composition after maternal bariatric surgery.

INTRODUCTION: In pregnancy after Roux-en-Y gastric bypass (RYGB), there is increased risk of low birthweight in the offspring. The present study examined how offspring body composition was affected by RYGB. MATERIAL AND METHODS: Mother-newborn dyads, where the mothers had undergone RYGB were included. Main outcome measure was neonatal body composition. Neonatal body composition was assessed by dual-energy X-ray absorptiometry scanning (DXA) within 48 hours after birth. In a statistical model offspring born after RYGB were compared with a reference material of offspring and analyses were made to estimate the effect of maternal pre-pregnancy body mass index (BMI), gestational weight gain, parity, gestational age at birth and newborn sex on newborn body composition. Analyses were made to estimate the impact of maternal weight loss before pregnancy and of other effects of bariatric surgery respectively. The study was performed at a university hospital between October 2012 and December 2013. RESULTS: We included 25 mother-newborn dyads where the mothers had undergone RYGB and compared them to a reference material of 311 mother-newborn dyads with comparable pre-pregnancy BMI. Offspring born by mothers after RYGB had lower birthweight (335g, p<0.001), fat-free mass (268g, p<0.001) and fat% (2.8%, p<0.001) compared with reference material. Only 2% of the average reduction in newborn fat free mass could be attributed to maternal pre-pregnancy weight loss whereas other effects of RYGB accounted for 98%. Regarding reduction in fat mass 52% was attributed to weight loss and 47% to other effects of surgery. CONCLUSION: Offspring born after maternal bariatric surgery, had lower birthweight, fat-free mass and fat percentage when compared with a reference material. RYGB itself and not the pre-pregnancy weight loss seems to have had the greatest impact on fetal growth.

Validity of bladder volume measurement by ultrasound in women postpartum.

INTRODUCTION: Vaginal birth increases the risk of urinary retention and overdistention of the bladder. To avoid unnecessary discomfort by catheterization, it is preferable to use ultrasound for diagnosis of these conditions. The aim of this study was to determine the validity of transabdominal ultrasound and a portable ultrasound system, Biocon-700, to measure bladder volume in women postpartum. METHODS: Fifty women were included in this method comparison study. Within 48 h of giving birth, their bladder volume was measured in randomized order with both transabdominal ultrasound and Biocon-700. After urination, participants were scanned with Biocon-700 to measure residual bladder volume, and finally the bladder was emptied by catheterization. The total bladder volume was calculated as the voided volume plus the catheterized volume. RESULTS: Biocon-700 measured 43.4 ml ± 117.4 ml (mean ± SD) lower than the total bladder volume, while volumes measured by transabdominal ultrasound were 117.8 ml ± 110.0 ml (mean ± SD) lower. Linear regression showed significant proportional bias in both methods. The Biocon-700 could detect a residual bladder volume > 150 ml with a positive predictive value of 66.7% and a negative predictive value of 100%. CONCLUSIONS: Neither transabdominal ultrasound nor the portable ultrasound system, Biocon-700, can be used to measure bladder volume precisely after vaginal delivery. However, both ultrasound methods can be used as screening tools to prevent overdistention of the bladder, and Biocon-700 can furthermore be used to screen women for a residual bladder volume > 150 ml.

The increasing role of a retained placenta in postpartum blood loss: a cohort study.

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.

The Impact of Upper Abdominal Pain During Pregnancy Following a Gastric Bypass.

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.

[Complications in pregnant women with polycystic ovary syndrome]. / Komplikationer hos gravide med polycystisk ovariesyndrom

Pregnant women with polycystic ovary syndrome (PCOS) are at increased risk of pregnancy-related disorders such as gestational diabetes (GDM), gestational hypertension and preeclampsia in the 2nd and 3rd trimester. In addition, the risk of preterm birth, children who are small and large for gestational age, caesarean section and poorer neonatal outcome seem to be elevated, however with less clear evidence. Except for the screening for GDM, there is no evidence of a benefit of increased surveillance during pregnancy for women with PCOS.

A Time Interval of More Than 18 Months Between a Pregnancy and a Roux-en-Y Gastric Bypass Increases the Risk of Iron Deficiency and Anaemia in Pregnancy.

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.

[Metformin and the obstetric patient]. / Metformin og obstetriske patienter

Polycystic ovary syndrome (PCOS) is associated with insulin resistance, infertility, obesity and gestational complications. Metformin is widely used in fertility treatment of women with PCOS, due to a suggested positive effect of continued metformin treatment beyond the first trimester on pregnancy complications. Larger randomized trials have failed to confirm this. Metformin treatment has not been found to be superior to insulin treatment in women with gestational diabetes and may be associated with long-term consequences in the children in the form of overweight and disturbed glucose metabolism.

The risk of adverse pregnancy outcome after bariatric surgery: a nationwide register-based matched cohort study.

OBJECTIVE: The aim of this study was to describe the risk of adverse obstetric and neonatal outcome after bariatric surgery. STUDY DESIGN: Nationwide register-based matched cohort study of singleton deliveries after bariatric surgery during 2004-2010. Data were extracted from The Danish National Patient Registry and The Medical Birth Register. Each woman with bariatric surgery (exposed) was individually matched with 4 women without bariatric surgery (unexposed) on body mass index, age, parity, and date of delivery. Continuous variables were analyzed with the paired t test and binary outcomes were analyzed by logistic regression. RESULTS: We identified 339 women with a singleton delivery after bariatric surgery (84.4% gastric bypass). They were matched to 1277 unexposed women. Infants in the exposed group had shorter mean gestational age (274 vs 278 days; P < .001), lower mean birthweight (3312 vs 3585 g; P < .001), lower risk of being large for gestational age (adjusted odds ratio, 0.31; 95% confidence interval, 0.15-0.65), and higher risk of being small for gestational age (SGA) (adjusted odds ratio, 2.29; 95% confidence interval, 1.32-3.96) compared with infants in the unexposed group. No statistically significant difference was found between the groups regarding the risk of gestational diabetes mellitus, preeclampsia, labor induction, cesarean section, postpartum hemorrhage, Apgar score less than 7, admission to neonatal intensive care unit or perinatal death. CONCLUSION: Infants born after maternal bariatric surgery have lower birthweight, lower gestational age, 3.3-times lower risk of large for gestational age, and 2.3-times higher risk of SGA than infants born by a matched group of women without bariatric surgery. The impact on SGA was even higher in the subgroup with gastric bypass.

High prevalence of type 2 diabetes and pre-diabetes in adult offspring of women with gestational diabetes mellitus or type 1 diabetes: the role of intrauterine hyperglycemia.

OBJECTIVE: The role of intrauterine hyperglycemia and future risk of type 2 diabetes in human offspring is debated. We studied glucose tolerance in adult offspring of women with either gestational diabetes mellitus (GDM) or type 1 diabetes, taking the impact of both intrauterine hyperglycemia and genetic predisposition to type 2 diabetes into account. RESEARCH DESIGN AND METHODS: The glucose tolerance status following a 2-h 75-g oral glucose tolerance test (OGTT) was evaluated in 597 subjects, primarily Caucasians, aged 18-27 years. They were subdivided into four groups according to maternal glucose metabolism during pregnancy and genetic predisposition to type 2 diabetes: 1) offspring of women with diet-treated GDM (O-GDM), 2) offspring of genetically predisposed women with a normal OGTT (O-NoGDM), 3) offspring of women with type 1 diabetes (O-type 1), and 4) offspring of women from the background population (O-BP). RESULTS: The prevalence of type 2 diabetes and pre-diabetes (impaired glucose tolerance or impaired fasting glucose) in the four groups was 21, 12, 11, and 4%, respectively. In multiple logistic regression analysis, the adjusted odds ratios (ORs) for type 2 diabetes/pre-diabetes were 7.76 (95% CI 2.58-23.39) in O-GDM and 4.02 (1.31-12.33) in O-type 1 compared with O-BP. In O-type 1, the risk of type 2 diabetes/pre-diabetes was significantly associated with elevated maternal blood glucose in late pregnancy: OR 1.41 (1.04-1.91) per mmol/l. CONCLUSIONS: A hyperglycemic intrauterine environment appears to be involved in the pathogenesis of type 2 diabetes/pre-diabetes in adult offspring of primarily Caucasian women with either diet-treated GDM or type 1 diabetes during pregnancy.

Audit on stillbirths in women with pregestational type 1 diabetes.

OBJECTIVE: To audit stillbirth cases in women with type 1 diabetes to search for specific characteristics in order to improve antenatal care and treatment. RESEARCH DESIGN AND METHODS: Retrospectively identified cases of stillbirths in women with type 1 diabetes during 1990-2000 were analyzed regarding characteristics of the mother, the pregnancy, glycemic control, and the stillborn. The cause of stillbirth was categorized as explainable, likely, or without obvious cause. RESULTS: We found 22 women with 25 stillbirths among 1,361 singleton births by women with type 1 diabetes. In seven stillbirths the cause was categorized as explainable and in six as likely. In 12 cases no obvious cause was found; however, glycemic control was suboptimal in 9 of these cases. A total of 14 women reported daily smoking, and 10 of 19 with low education were unemployed. CONCLUSIONS: Women experiencing stillbirth were characterized by a high incidence of suboptimal glycemic control, diabetic nephropathy, smoking, and low social status.