Comparative Studies of the Gut Microbiota in the Offspring of Mothers With and Without Gestational Diabetes.

Background: Offspring of mothers with gestational diabetes mellitus (GDM) have increased risk of developing metabolic disorders as they grow up. Microbial colonization of the newborn gut and environmental exposures affecting the configuration of the gut microbiota during infancy have been linked to increased risk of developing disease during childhood and adulthood. In a convenience sample, we examined whether the intestinal tract of children born to mothers with GDM is differentially colonized in early life compared to offspring of mothers with normal gestational glucose regulation. Secondly, we examined whether any such difference persists during infancy, thus potentially conferring increased risk of developing metabolic disease later in life. Methods: Fecal samples were collected from children of mothers with (n = 43) and without GDM (n = 82) during the first week of life and again at an average age of 9 months. The gut microbiota was characterized by 16S rRNA gene amplicon sequencing (V1-V2). Differences in diversity and composition according to maternal GDM status were assessed, addressing potential confounding by mode of delivery, perinatal antibiotics treatment, feeding and infant sex. Results: Children of mothers with GDM were featured by a differential composition of the gut microbiota, both during the first week of life and at 9 months, at higher taxonomic and OTU levels. Sixteen and 15 OTUs were differentially abundant after correction for multiple testing during the first week of life and at 9 months, respectively. Two OTUs remained differentially abundant after adjustment for potential confounders both during the first week of life and at 9 months. Richness (OTU) was decreased in neonates born to mothers with GDM; however, at 9 months no difference in richness was observed. There was no difference in Shannon's diversity or Pielou's evenness at any timepoint. Longitudinally, we detected differential changes in the gut microbiota composition from birth to infancy according to GDM status. Conclusion: Differences in glycaemic regulation in late pregnancy is linked with relatively modest variation in the gut microbiota composition of the offspring during the first week of life and 9 months after birth.

Prevalence and treatment of group B streptococcus colonization based on risk factors versus intrapartum culture screening.

OBJECTIVES: To estimate the prevalence of group B streptococcus at onset of labor and to compare the accuracy of intrapartum antibiotic prophylaxis based on a risk factor strategy versus an intrapartum screening. STUDY DESIGN: In this cross-sectional study, 700 women referred for intended vaginal delivery were tested for group B streptococcus at onset of labor by gold standard culture in vaginal and rectal swabs. The results were blinded, and intrapartum antibiotic prophylaxis was given to women with risk factors for group B streptococcus infection: previous neonatal group B streptococcus infection, group B streptococcus in urine and/or vagina in current pregnancy, gestational age <36 + 0 weeks, temperature ≥38.0 °C or rupture of membranes ≥18 h. RESULTS: Of 642 women, who delivered within three days of specimen collection, 170 (26.5%) received benzylpenicillin as intrapartum antibiotic prophylaxis based on risk factors. The prevalence of group B streptococcus at onset of labor was 17.8% (114/642), with 62 women positive for group B streptococcus in both the vagina and rectum, 12 in the vagina only and 40 in rectum only. Intrapartum antibiotic prophylaxis was administered correctly in 31.6% (36/114) of GBS positive women at time of delivery and 78.8% (134/170) of women who received antibiotics were actually GBS negative. The positive predictive value of intrapartum antibiotic prophylaxis based on risk factors was 21.2%. The sensitivity was 31.6% and the specificity was 74.6%. CONCLUSION: The accuracy of predicting maternal group B streptococcus infection from risk factors is low. Intrapartum group B streptococcus diagnostics is more precise and will not increase the overall use of intrapartum antibiotic prophylaxis.

[Posterior reversible encephalopathy syndrome - an MRI diagnosis often missed in pregnancy].

Posterior reversible encephalopathy syndrome (PRES) is a complex clinical condition with a wide clinical spectrum. In this report two cases illustrate two different onsets. The first patient presented with general seizures, whereas the other presented with symptoms of pre-eclampsia, which developed into sudden blindness. Both patients had uneventful caesarean sections performed, with delivery of healthy children. Due to CT scans of the cerebrum, correct treatment and diagnosis were delayed in both cases, but subsequently, PRES was confirmed by MRI. Both patients were discharged in good health.

Gestational diabetes is associated with change in the gut microbiota composition in third trimester of pregnancy and postpartum.

BACKGROUND: Imbalances of gut microbiota composition are linked to a range of metabolic perturbations. In the present study, we examined the gut microbiota of women with gestational diabetes mellitus (GDM) and normoglycaemic pregnant women in late pregnancy and about 8 months postpartum. METHODS: Gut microbiota profiles of women with GDM (n = 50) and healthy (n = 157) pregnant women in the third trimester and 8 months postpartum were assessed by 16S rRNA gene amplicon sequencing of the V1-V2 region. Insulin and glucose homeostasis were evaluated by a 75 g 2-h oral glucose tolerance test during and after pregnancy. RESULTS: Gut microbiota of women with GDM was aberrant at multiple levels, including phylum and genus levels, compared with normoglycaemic pregnant women. Actinobacteria at phylum level and Collinsella, Rothia and Desulfovibrio at genus level had a higher abundance in the GDM cohort. Difference in abundance of 17 species-level operational taxonomic units (OTUs) during pregnancy was associated with GDM. After adjustment for pre-pregnancy body mass index (BMI), 5 of the 17 OTUs showed differential abundance in the GDM cohort compared with the normoglycaemic pregnant women with enrichment of species annotated to Faecalibacterium and Anaerotruncus and depletion of species annotated to Clostridium (sensu stricto) and to Veillonella. OTUs assigned to Akkermansia were associated with lower insulin sensitivity while Christensenella OTUs were associated with higher fasting plasma glucose concentration. OTU richness and Shannon index decreased from late pregnancy to postpartum regardless of metabolic status. About 8 months after delivery, the microbiota of women with previous GDM was still characterised by an aberrant composition. Thirteen OTUs were differentially abundant in women with previous GDM compared with women with previous normoglycaemic pregnancy. CONCLUSION: GDM diagnosed in the third trimester of pregnancy is associated with a disrupted gut microbiota composition compared with normoglycaemic pregnant women, and 8 months after pregnancy, differences in the gut microbiota signatures are still detectable. The gut microbiota composition of women with GDM, both during and after pregnancy, resembles the aberrant microbiota composition reported in non-pregnant individuals with type 2 diabetes and associated intermediary metabolic traits.

Successfully reducing newborn asphyxia in the labour unit in a large academic medical centre: a quality improvement project using statistical process control.

BACKGROUND: A safe delivery is part of a good start in life, and a continuous focus on preventing harm during delivery is crucial, even in settings with a good safety record. In January 2013, the labour unit at Copenhagen University Hospital, Hvidovre, undertook a quality improvement (QI) project to prevent asphyxia and reduced the percentage of newborns with asphyxia by 48%. METHODS: The change theory consisted of two primary elements: (1) the clinical content, including three clinical bundles of evidence-based care, a 'delivery bundle', an 'oxytocin bundle' and a 'vacuum extraction bundle'; (2) an implementation theory, including improving skills in interpretation of cardiotocography, use of QI methods and participation in a national learning network. The Model for Improvement and Deming's system of profound knowledge were used as a methodological framework. Data on compliance with the care bundles and the number of deliveries between newborns with asphyxia (Apgar <7 after 5 min or pH <7) were analysed using statistical process control. RESULTS: Compliance with all three clinical care bundles improved to 95% or more, and the percentages of newborns with pH <7 and Apgar <7 after 5 min were reduced by 48% and 31%, respectively. In general, the QI approach strengthened multidisciplinary teamwork, systematised workflow and structured communication around the deliveries. Changes included making a standard memo in the medical record, the use of a bedside whiteboard, bedside handovers, shared decisions with a peer when using an oxytocin infusion and the use of a checklist before vacuum extractions. CONCLUSION: This QI project illustrates how aspects of patient safety, such as the prevention of asphyxia, can be improved using QI methods to more reliably implement best practice, even in high-performing systems.

[Treatment with low-dose acetylsalicylic acid can reduce risk of pre-eclampsia in high-risk pregnant women].

Pre-eclampsia is a major contributor to perinatal morbidity and mortality. Large studies of high-risk pregnant women have shown reduced risk of developing pre-eclampsia when they are treated with low-dose acetylsalicylic acid in early pregnancy. Treatment is also effective in preventing intrauterine growth restriction, preterm birth and perinatal death. No major side effects, including risk of malformations or miscarriage, are reported. It is important that general practitioners are aware of women who have an increased risk of developing pre-eclampsia, so that treatment with 100 mg of acetylsalicylic acid can be started early in pregnancy.

Lactate versus pH levels in fetal scalp blood during labor--using the Lactate Scout System.

OBJECTIVE: To assess if lactate measured with the Scout Lactate System is a reliable alternative to pH in intrapartum monitoring of the fetus. METHODS: A prospective study analyzing (1) the correlation between scalp lactate measured by the Scout Lactate System and the Automatic Blood Laboratory (ABL), (2) the correlation between lactate and pH measured in scalp blood and (3) the correlation between fetal scalp lactate and umbilical cord SBE. The sensitivity/specificity and positive/negative predictive values of lactate in predicting low pH were analyzed and expressed as Receiver Operating Curves (ROC). RESULTS: Lactate measured by the Scout Lactate System and the ABL correlated well (r(2)=0.85). Both lactate and pH were measured in 1009 scalp blood samples. The sensitivity and specificity of lactate ≥ 4.8 mmol/l in predicting a pH <7.20 were 0.63 and 0.85, respectively. The correlation between scalp lactate measured within 15 min prior to delivery and the umbilical cord SBE was low. CONCLUSION: Monitoring non-reassuring deliveries with scalp lactate instead of pH would have resulted in more (155 instead of 56) instrumental deliveries with no decrease in newborns with severe metabolic acidosis.

Validity of a hospital-based obstetric register using medical records as reference.

BACKGROUND: Data from hospital-based registers and medical records offer valuable sources of information for clinical and epidemiological research purposes. However, conducting high-quality epidemiological research requires valid and complete data sources. OBJECTIVE: To assess completeness and validity of a hospital-based clinical register - the Obstetric Database - using a national register and medical records as references. METHODS: We assessed completeness of a hospital-based clinical register - the Obstetric Database - by linking data from all women registered in the Obstetric Database as having given birth in 2013 to the National Patient Register with coverage of all births in 2013. Validity of eleven selected indicators from the Obstetric Database was assessed using medical records as a golden standard. Using a random sample of 250 medical records, we calculated proportion of agreement, sensitivity, specificity, and positive and negative predictive values for each indicator. Two assessors independently reviewed medical records and inter-rater reliability was calculated as proportion of agreement and Cohen's κ coefficient. RESULTS: We found 100% completeness of the Obstetric Database when compared to the Danish National Patient Register. Except for one delivery all 6,717 deliveries were present in both registers. Proportion of agreement between the Obstetric Database and medical records ranged from 91.1% to 99.6% for the eleven indicators. The validity measures ranged from 0.70 to 1.00 indicating high validity of the Obstetric Database. κ coefficients from the inter-rater reliability ranged from 0.71 to 1.00. CONCLUSION: Completeness and validity of the Obstetric Database were found acceptable when using the National Patient Register and medical records as golden standards. The Obstetric Database therefore offers a valuable source for examining clinical, administrative, and research questions.

Treating Psoriasis During Pregnancy: Safety and Efficacy of Treatments.

Psoriasis is a chronic inflammatory disease with a well-documented negative effect on the quality of life of affected patients. Psoriasis often occurs in the reproductive years, during which the issue of pregnancy needs to be addressed. The course of psoriasis during pregnancy is unpredictable, and many patients face the challenge of needing treatment during pregnancy. In this review we provide an overview of the key considerations for managing psoriasis in pregnant women, covering the potential effects of active psoriasis and co-morbid conditions on the health of the mother and fetus, as well as the effects of psoriasis treatment options on the developing fetus. Although there are no robust data on the safety of systemic treatment of pregnant women, increasing evidence regarding the safety of cyclosporine (ciclosporin) treatment as well as anti-tumor necrosis factor-α is available and should be considered in pregnant women with moderate to severe psoriasis unresponsive to local corticosteroids and UVB light treatment.

[Raynaud's phenomenon of the papilla mammae caused by breastfeeding]. / Ammeudløst Raynauds fænomen i papilla mammae.

In Denmark, the benefits of breastfeeding are emphasized and the Danish Health and Medicines Authority encourages women to breastfeed for at least six months. Raynaud's phenomenon can occur in any small arteriole and cause painful, temporary ischaemia. Women quit breastfeeding prematurely for a variety of reasons, pain being just one of them. In this case report we describe an incident of Raynaud's phenomenon of the nipple and describe how correct diagnosis can prevent unnecessary medical treatment and cause relief of symptoms, thus avoiding premature cessation of breastfeeding.

Do women with a repeat termination of pregnancy prefer a medical or a surgical regimen?

We compared the risk of a repeat termination and the method of termination in women with a prior medical or surgical termination, or both, in a cohort study of women with a pregnancy termination at gestational age ≤63 days in 1999-2001. Within 5 years, 24% (330/1379) had a repeat abortion, and repeat terminations were more frequent in the surgical [27% (159/588)] than the medical group [22% (171/791)] (p < 0.05). The method used at the repeat termination was medical in 49% (83/171) of women with an earlier medical termination, compared with 13% (21/159) (p < 0.01) in women with an earlier surgical termination. In 125 women who had experienced both procedures, 37% (46/125) of the next terminations were performed medically and 63% (79/125) surgically (p < 0.01). Women in our study with a repeat termination tended to choose the same method as used before, and more often a surgical termination.

Comparison of gemeprost and vaginal misoprostol in first trimester mifepristone-induced abortion.

BACKGROUND: The aim of this study was to compare efficacy and side effects of gemeprost and vaginal misoprostol in mifepristone-induced abortions in women up to 63 days of gestation. METHODS: A retrospective study of 833 consecutive patients admitted for medical termination of first trimester pregnancy was conducted. Four-hundred ten patients received mifepristone 600 mg, followed 48 h later by gemeprost 1 mg (regimen I), and 423 patients received mifepristone 200 mg followed by vaginal misoprostol 800 microg (regimen II). Success rates were evaluated after 2 weeks and after 3 months. The severity of bleeding and side effects (pain, nausea, vomiting and diarrhea) was scored by the patients, and requests for supplementary analgesic treatment were recorded by the attending nurse. RESULTS: Success rates were 99% in both groups after 2 weeks of follow-up. At 3 months of follow-up, success rates had declined to 94% for regimen I and 96% for regimen II. The frequency of severe pain was higher in regimen I compared to regimen II (72% vs. 60%, p < .001), but the severity of bleeding and gastrointestinal side effects was similar in the two regimens. CONCLUSION: When combined with mifepristone, gemeprost and vaginal misoprostol are equally effective for termination of first trimester abortion, but may be associated with varying intensity of side effects.

Medical versus surgical abortion: comparing satisfaction and potential confounders in a partly randomized study.

BACKGROUND: The aim of the study was to compare satisfaction with medical and surgical abortion and to identify potential confounders affecting satisfaction. METHODS: 1033 women with gestational age (GA) < or = 63 days had either a medical (600 mg mifepristone followed by 1 mg gemeprost) or a surgical abortion (vacuum aspiration in general anaesthesia). The procedure was determined either by randomization (n = 111) or by choice (n = 922). Data on satisfaction, side effects and expectations were collected from questionnaires 2 and 8 weeks after termination. RESULTS: More women were very satisfied or satisfied after a surgical than a medical abortion both after choosing method (92% vs 82%, P < 0.0001), and after randomization (94% vs 68%, P < 0.001). Satisfaction was higher after choosing a medical procedure than after randomization to the same procedure; 82% and 68%, respectively, P < 0.05. Satisfaction with the medical procedure was inversely correlated with GA and the intensity of pain, nausea, vomiting and dizziness, while satisfaction with the surgical procedure was unaffected by these side effects. Fewer women with a failed medical than a failed surgical abortion were satisfied (17% vs 62%), P < 0.05. CONCLUSIONS: Satisfaction with both medical and surgical abortions is high, although higher with the surgical than the medical procedure, and higher after choosing method than after randomization.

Sexual behavior during the first eight weeks after legal termination of pregnancy.

BACKGROUND: The aim of the study was to describe sexual symptoms and resumption of sexual activity during the first 8 weeks after unrestricted first-trimester termination of pregnancy (TOP). METHODS: Questionnaires 2 and 8 weeks after legal first-trimester abortion in 1327 women. RESULTS: The 8-week questionnaire was returned by 941 (71%). Overall, 51.0% of the women recommenced coitus within 2 weeks after TOP. This figure was significantly higher among women aged 18-24 years (60.6%) than among women in higher age groups (41.7-47.8%). At 8 weeks follow-up coitus was reported by 86.9%, ranging from 65.8% of women not in a steady relationship to 93.7% of women in a relationship (p < 0.001), and age-related differences were insignificant. Long duration of vaginal bleeding, medical abortion and need for reevacuation of the uterus diminished the resumption frequency at 2 weeks follow-up, but 8 weeks after termination postabortion complications did not affect resumption. At 8 weeks follow-up 15.3% reported diminished sexual desire and 6.0% reported diminished orgasm ability comparing to prepregnancy level. Of the sexually active women 6.2% did not use sufficient contraception 8 weeks after termination. CONCLUSION: Coitus is recommenced shortly after termination of pregnancy but not always with sufficient contraception. Legal abortion is associated with few adverse effects on sexual function.

Medical versus surgical abortion efficacy, complications and leave of absence compared in a partly randomized study.

To provide optimal information to women choosing between early medical and surgical abortion, rigorous comparisons of the two methods are warranted. We compared the outcome of 1135 consecutive women with gestational age (GA) < or = 63 days receiving either a medical (600 mg mifepristone and 1 mg gemeprost) or a surgical abortion (vacuum aspiration in general anesthesia). One hundred eleven of these women were randomized for abortion method. Surgical interventions and complications leading to readmission within the following 15 weeks were identified through a computer system. Information about antibiotic treatment, leave of absence and number of contacts to the health care system were obtained from mailed questionnaires. The number of complications was identical after the two methods, but surgical abortion was associated with a higher success rate [97.7% (708/725) vs. 94.1% (386/410), p < .01] and also with a higher risk of antibiotic treatment than medical abortion [7.8% (37/467) vs. 3.7% (13/356), p < .05]. The median leave of absence was shorter in women choosing a medical (1 day) than a surgical termination (2 days), p < .05. On average, one third of all the women requested at least one extra unscheduled consultation apart from a routine follow-up visit. We conclude that the chance of a primary successful termination at GA < or = 63 days is higher after a surgical abortion in general anesthesia compared to a medical abortion induced with 600 mg mifepristone and 1 mg gemeprost. A surgical abortion is associated with an increased risk of antibiotic treatment compared to medical abortion. The women's need for follow-up might be higher than we expect.

Medical abortion. defining success and categorizing failures.

Medical abortion was performed in 461 consecutive women with gestational age

[Large variation in clinical regimens use to induce medical abortion in Denmark]. / Stor variation i behandlingsregimener ved medicinsk abort i Danmark.

INTRODUCTION: Medical abortion was introduced in Denmark in 1997. The purpose of the present study was to describe the use of medical abortion and the applied regimens. MATERIAL AND METHODS: Late 2000, questionnaires were sent to all gynecological and surgical departments in Denmark performing abortions. RESULTS: Late 2000, medical abortion was performed in 25 of the approximately 50 departments performing abortion. In the majority of cases the method was introduced during 1999 and the estimated frequency of medical termination was 25% of all first trimester abortions in the departments offering the method. All departments used a combination of mifepristone and either misoprostol or gemeprost. Doses and administration, upper gestational limit, and follow-up procedures showed great variation between the departments. Medical abortion was in general considered an equal but more expensive method than surgical termination. DISCUSSION: The literature describes many different ways to induce medical abortion, but only parts of the regimens have been evaluated in randomised controlled trials and the results are difficult to transfer directly to Danish conditions. The variation in regimens used in Denmark reflects the lack of consensus on an optimal procedure. We look forward to the national guidelines in the area, which will enable us to compare and optimise the procedure more easily.

HLA-G allelic variants are associated with differences in the HLA-G mRNA isoform profile and HLA-G mRNA levels.

During pregnancy, the human extra-villous trophoblast in the contact zone between maternal and fetal tissue in the placenta does not express the classical MHC class I and II molecules. Instead, HLA-G and -C, and possibly HLA-E, are expressed. HLA-G may modulate the immunological relationship between mother and fetus in several ways. Finally, the expression of membrane-bound HLA-G and soluble HLA-G has been proposed to influence the outcome of pregnancy, and an aberrant HLA-G expression in pre-eclamptic placentas and spontaneous abortions has been reported. Here, an association between certain HLA-G polymorphisms and the mRNA levels of the different alternatively spliced HLA-G isoforms in first trimester trophoblast cell populations is reported. Several alternatively spliced HLA-G mRNA isoforms, including a 14-bp polymorphism in the 3'UTR end (exon 8) of the HLA-G gene, are expressed at a significantly lower level than the corresponding HLA-G mRNA isoforms with the 14-bp sequence deleted. Furthermore, characteristic HLA-G mRNA isoform expression patterns were associated with specific HLA-G genotypes and alleles. In the HLA-G*01012 and - G*01013 alleles that include the 14-bp sequence, an additional alternative splicing was observed, with the first 92-bp of exon 8 spliced out. This was most pronounced in HLA-G genotypes with G*01013. These findings may have functional implications for the recent reports of aberrant HLA-G expression and reproductive success.