GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5-2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility.

Knowledge, challenges, and standard of care of young women with ADHD at Swedish youth clinics.

OBJECTIVES: Sexual risk-taking and its consequences for young women with ADHD(attention deficit hyperactivity disorder) including sexually transmitted diseases, teenage pregnancies and underage parenthood constitute substantial challenges for individuals and midwives. The aim was to investigate current knowledge and specific challenges in reproductive health and contraceptive counselling for women with ADHD at Swedish youth clinics. METHOD: Inductive qualitative interview study of ten midwives at six youth health clinics in Stockholm and Uppsala County. We used a semi-structured interview guide. The interviews were transcribed verbatim and analyzed with the NVivo 12 qualitative data analysis software. RESULTS: Three main categories were identified: (1) challenges in provision of care of young women with ADHD, (2) standard of care and active adaptations towards women with ADHD and (3) organizational readiness for change;. Several challenges and frustrations, such as difficulties with attention with or without concomitant impulsivity and overactivity, in provision of reproductive health and contraceptive counselling for young women with ADHD were identified. Midwives reported high organizational readiness for improvement of standard of care. CONCLUSIONS: Inadequate contraceptive counseling or lack of knowledge on specific challenges in the sexual and reproductive health of young women with ADHD may contribute to this group failing to access, inadequately respond to, or act upon counseling at youth clinics. Support for midwives with evidence-based interventions specifically developed for these women are imperative. Development of such tools should be a priority for research.

Alcohol and illicit and non-medical prescription drug use before and during pregnancy in Stockholm, Sweden: A cross-sectional study.

OBJECTIVES: To provide current estimates of alcohol and drug use among pregnant women attending antenatal care lectures in preparation for childbirth in Stockholm, Sweden. STUDY DESIGN: A cross-sectional study. Data was collected anonymously among women attending lectures in preparation for childbirth. MAIN OUTCOME MEASURES: The prevalence of alcohol and illicit and non-medical prescription drug use among pregnant women attending antenatal care lectures in preparation for childbirth. RESULTS: Nine hundred and thirty-six pregnant women attending lectures in preparation for childbirth participated. Among those answering all questions about alcohol use during pregnancy, 4.2 percent reported use (95% confidence interval (CI), 3.0-5.7%) and among those answering all questions about illicit or non-medical prescription drug use during pregnancy, 0.5 percent reported such use (95% CI, 0.1-1.3%). The prevalences of binge drinking during pregnancy and alcohol and drug use before pregnancy are presented. Comparisons of anonymously and non-anonymously collected data are included. CONCLUSIONS: Approximately one in 25 women reported using alcohol and approximately one in 200 reported using illicit or non-medical prescription drugs while pregnant. Alcohol use during pregnancy may have decreased in Stockholm, Sweden.

Potentially traumatic events, fear of childbirth and posttraumatic stress disorder during pregnancy in Stockholm, Sweden: A cross-sectional study.

OBJECTIVES: To estimate the prevalence of potentially traumatic events (PTEs), fear of childbirth (FOC), and support for it as well as posttraumatic stress disorder (PTSD) among pregnant women attending maternal care in Stockholm, Sweden. METHODS: A cross-sectional study was conducted. Pregnant women attending lectures in preparation for childbirth at the major hospitals in Stockholm were asked to complete questionnaires anonymously. Main outcome measures were the prevalence of PTEs, FOC, support for FOC and PTSD. RESULTS: One thousand one hundred fifty-seven women in late pregnancy attending lectures in preparation for childbirth at hospitals in Stockholm, Sweden, were asked to participate, 945 chose to participate, resulting in a response rate of 81.7 percent. Most pregnant women, 78.5 percent (95% confidence interval (CI) 75.6-81.3), reported having experienced at least one PTE. The prevalence of having experienced different types of violence is presented. FOC was found among 28.8 percent (95% CI 25.7-32.0) of pregnant women, while only 10.9 percent (95% CI 10.5-11.2) received support for FOC. The prevalence of current PTSD was 4.1 percent (95% CI 2.8-5.8). CONCLUSIONS: The majority of pregnant women had experienced PTEs, and experiences of violence were common, as was FOC. Approximately one in 25 women attending general maternal care in Stockholm, Sweden, was estimated to have current PTSD. This highlights the need to prevent violence, find pregnant women suffering from FOC or PTSD, to develop an evidence-based treatment for FOC and to provide such treatment for PTSD.

Colposcopy telemedicine: live versus static swede score and accuracy in detecting CIN2+, a cross-sectional pilot study.

BACKGROUND: This cross-sectional pilot study evaluates diagnostic accuracy of live colposcopy versus static image Swede-score evaluation for detecting significant precancerous cervical lesions greater than, or equal to grade 2 severity (CIN2+). METHODS: VIA or HrHPV positive women were examined using a mobile colposcope, in a rural clinic in Kolkata, India. Live versus static Swede-score colposcopy assessments were made independently. All assessments were by gynecologists, junior or expert. Static image assessors were blinded to live scoring, patient information and final histopathology result. Primary outcome was the ability to detect CIN2+ lesions verified by directed biopsies. Diagnostic accuracy was calculated for live versus static Swede-score in detecting CIN2+ lesions, as well as for interclass correlation. RESULTS: 495 images from 94 VIA positive women were evaluated in this study. Thirteen women (13.9%) had CIN2+ on biopsy. No significant difference was found in the detection of CIN2+ lesions between live and static assessors (area under curve = 0.69 versus 0.71, p = 0.63). A Swede-score of 4+, had a sensitivity of 76.9% (95% CI 46.2-95.0%) and 84.6% (95% CI 54.6-98.1%), for live- and static-image assessment respectively. The corresponding positive predictive values were found to be 90.9% (95% CI 75.7-98.1%) and 92.6% (95% CI 75.7-99.1%). The interclass correlation was good (kappa statistic = 0.60) for the senior static assessors. CONCLUSIONS: Swede-score evaluation of static colposcopy images was found to reliably detect CIN2+ lesions in this study. Larger studies are needed to further develop the colposcopy telemedicine concept which may offer reliable guidance in management where direct specialist input is not available. TRIAL REGISTRATION: Ethical approval of the study was obtained by the Chittaranjan National Cancer Institute (CNCI) Human Research Ethics Committee (4.311/27/2014). The trial was retrospectively registered in the Clinical Trails Registry of India CTRI/2018/03/012470 .

Cardiac function, myocardial mechano-energetic efficiency, and ventricular-arterial coupling in normal pregnancy.

OBJECTIVE: To assess cardiac function, myocardial mechanoenergetic efficiency (MEE), and ventricular-arterial coupling (VAC) longitudinally during normal pregnancy, and to study if there was an association between cardiac structure and function, and fetal growth. METHODS: Cardiac structure and function, MEE, and ventricular-arterial coupling was assessed longitudinally in 52 healthy nulliparous women at 14, 24, and 34 weeks' gestation and 9-month postpartum. RESULTS: Left atrial diameter increased during pregnancy (30.41 ±â€Š3.59 mm in the nonpregnant state and 31.02 ±â€Š3.91, 34.06 ±â€Š3.58, and 33.9 ±â€Š2.97 mm in the first, second, and third trimesters, P < 0.001). Left ventricular mass increased 117.12 ±â€Š45.0 g in the nonpregnant state and 116.5 ±â€Š33.0, 126.9 ±â€Š34.5, 128.4 ±â€Š36 g in the first, second, and third trimesters (P < 0.001). Cardiac output increased from 3.4 ±â€Š1.2 l/min to 4.3 ±â€Š0.7 l/min in the second and third trimesters (P < 0.001). Diastolic function decreased as both E/A and e'/a' decreased during pregnancy (P < 0.05 and P < 0.001, respectively). MEE and VAC were retained during pregnancy. Heart rate was associated with birth weight centile in the first (r = 0.41, P = 0.002) and second (r = 0.46, P = 0.002) trimester. CONCLUSION: The increase in cardiac output during normal pregnancy is obtained by an increase in heart rate, followed by structural cardiac changes. The impaired systolic function is accomplished by a deteriorated diastolic function. Despite these rapid changes, the myocardium manages to work efficient with a preserved MEE. Cardiac and arterial adaption to pregnancy seems to appear parallel as evidenced by a preserved VAC.

Diagnostic colposcopic accuracy by the gynocular and a stationary colposcope.

OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy of sensitivity and specificity of cervical lesions by the low-cost, portable Gynocular colposcope and a stationary colposcope, in women referred for colposcopy with abnormal cervical cytology. METHODS: A randomized cross-over clinical trial for evaluating the diagnostic accuracy in detecting cervical lesions by the Gynocular and a stationary colposcope. The Swede score systematic colposcopy system was used for evaluation of colposcopic abnormalities. Directed punch biopsy and excisional cone biopsy were used as the "gold-standard" by histologically confirmed high grade cervical lesions CIN2+ (CIN2, CIN3, CIN3+). In total, 123 women referred for colposcopy due to abnormal cervical cytology were recruited at the Department of Obstetrics and Gynecology, Danderyd Hospital, Stockholm, Sweden. The percentage agreement and the kappa statistic were calculated for Swede score by the Gynocular and a stationary colposcope. Swede scores were compared with the results from directed punch biopsy and excisional cone biopsy. RESULTS: The Gynocular and the stationary colposcope had a high agreement of Swede scores with a Kappa statistic of 0.947, p < .0001. Punch biopsy diagnosed CIN2+ (CIN2, CIN3, and invasive cancer) in 44 (35.7 percent) women while cytology detected CIN2+ in 34 (27.6 percent) women. There were no significant differences of the sensitivity and specificity for different Swede scores by the Gynocular or a stationary colposcope in detecting CIN 2+. CONCLUSIONS: There were no significant differences in sensitivity or specificity in detecting cervical lesions by the Gynocular or stationary colposcope. The Gynocular is as accurate in diagnosing cervical lesions as a stationary colposcope.

Intrahepatic cholestasis of pregnancy and cancer, immune-mediated and cardiovascular diseases: A population-based cohort study.

BACKGROUND & AIMS: Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease in pregnancy. It is associated with hepatobiliary diseases that might predispose to cancer and also with gestational diabetes and preeclampsia. In this study, we examined associations between ICP and cancer, and immune-mediated and cardiovascular diseases. METHODS: By linking the Swedish Medical Birth Register and the Swedish Patient Register, we identified 11,388 women with ICP and 113,893 matched women without ICP who gave birth between 1973 and 2009. Diagnoses of cancer and immune-mediated and cardiovascular diseases both before and after delivery were obtained from the Patient Register. The main outcome measures were hazard ratios (HRs), calculated through Cox regression, for the indicated diseases after delivery. RESULTS: ICP was not associated with later overall cancer (HR 1.07, 95% confidence interval [CI] 0.94-1.21), but it was associated with later liver and biliary tree cancer (HR 3.61, 95% CI 1.68-7.77, and 2.62, 95% CI 1.26-5.46, respectively). ICP was also associated with later immune-mediated diseases (HR 1.28, 95% CI 1.19-1.38), and specifically diabetes mellitus (HR 1.47, 95% CI 1.26-1.72), thyroid disease (HR 1.30, 95% CI 1.14-1.47), psoriasis (HR 1.27, 95% CI 1.07-1.51), inflammatory polyarthropathies (HR 1.32, 95% CI 1.11-1.58) and Crohn's disease (HR 1.55, 95% CI 1.14-2.10), but not ulcerative colitis (HR 1.21, 95% CI 0.93-1.58). Women with ICP also had a small increased risk of later cardiovascular disease (HR 1.12, 95% CI 1.06-1.19). CONCLUSIONS: Women with ICP have increased risk of later hepatobiliary cancer and immune-mediated and cardiovascular diseases.

Evaluation of the accuracy in detecting cervical lesions by nurses versus doctors using a stationary colposcope and Gynocular in a low-resource setting.

OBJECTIVES: Evaluation of the performance of VIA (visual inspection with acetic acid) trained nurses to learn colposcopy and the Swede score method to detect cervical lesions by using stationary colposcope or a portable, hand-held colposcope; the Gynocular, as compared to doctors. DESIGN: A crossover randomised clinical trial. SETTING: The Colposcopy Clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. PARTICIPANTS: 932 women attending the clinic as either screening naïve for VIA screening (404) or women referred as VIA positive (528) from other VIA screening centres in the Dhaka region. INTERVENTION: VIA trained nurses were trained on-site in colposcopy and in the Swede score systematic colposcopy method. The Swede score grade cervical acetowhiteness, margins plus surface. vessel pattern, lesion size and iodine staining. The women were randomised to start the examination by either a stationary colposcope or the Gynocular. Swede scores were first obtained by a nurse and the same patient was equally evaluated by a doctor. PRIMARY AND SECONDARY OUTCOME MEASURES: Agreement between nurses and doctors in Swede scores was evaluated using the weighted κ statistic for the Gynocular and standard colposcope. The ability to predict CIN 2+ (CIN 2, CIN 3 and invasive cervical cancer) using Swede scores was evaluated using receiver-operating characteristic curves. RESULTS: The Swede scores obtained by nurses and doctors using the Gynocular and stationary colposcope showed high agreement with a κ statistic of 0.858 and 0.859, respectively, and no difference in detecting cervical lesions in biopsy. Biopsy detected CIN 2+ in 39 (4.2%) women. CONCLUSIONS: Our study showed that VIA nurses can perform colposcopy. There was no significant differences compared to doctors in detecting cervical lesions by stationary colposcope or the Gynocular using the Swede score system. Swede scores obtained by nurses using the Gynocular could offer an accurate cervical diagnostic approach in low resource settings. TRIAL REGISTRATION NUMBER: ISRCTN53264564.

Evaluation of stationary colposcope and the Gynocular, by the Swede score systematic colposcopic system in VIA positive women: a crossover randomized trial.

OBJECTIVE: This study aimed to evaluate cervical lesions by the Swede coloscopy system, histologic finding, liquid-based cytology, and human papillomavirus (HPV) in women who resulted positive for visual inspection of the cervix with acetic acid (VIA) by using a pocket-sized battery-driven colposcope, the Gynocular (Gynius AB, Sweden). METHODS: This study was a crossover, randomized clinical trial at the colposcopy clinic of Bangabandhu Sheikh Mujib Medical University in Dhaka, Bangladesh, with 540 VIA-positive women. Swede scores were obtained by the Gynocular and stationary colposcope, as well as samples for liquid-based cytology, HPV, and cervical biopsies. The Swede scores were compared against the histologic diagnosis and used as criterion standard. The percentage agreement and the κ statistic for the Gynocular and standard colposcope were also calculated. RESULTS: The Gynocular and stationary colposcope showed high agreement in Swede scores with a κ statistic of 0.998, P value of less than 0.0001, and no difference in detecting cervical lesions in biopsy. Biopsy detected cervical intraepithelial neoplasia (CIN) 2+ (CIN2, CIN3, and invasive cancer) in 38 (7%) of the women, whereas liquid-based cytology detected CIN2+ in 13 (2.5%) of the women. Forty-four (8.6%) women who were tested resulted positive for HPV; 20 (3.9%) women had HPV-16, 2 (0.4%) had HPV-18, and 22 (4.3%) had other high-risk HPV. CONCLUSIONS: Our study showed that few VIA-positive women had CIN2+ lesions or HPV infection. Colposcopy by Swede score identified significantly more CIN2+ lesions than liquid-based cytology and could offer a more accurate screening and selection for immediate treatment of cervical lesions in low-resource settings.

Agreement of colposcope and gynocular in assessment of cervical lesions by swede score: a randomized, crossover pilot trial.

OBJECTIVE: This study aimed to determine if criterion standard colposcopy could be provided by a pocket-sized battery-driven colposcope, the Gynocular. MATERIALS AND METHODS: The study was a randomized, crossover, pilot clinical trial for evaluating agreement of diagnosis of cervical lesions by colposcopy using a standard colposcope and a pocket-sized battery-driven colposcope, the Gynocular, in 69 women positive for visual inspection with acetic acid. Swede scores were used at the time of colposcopy and compared with the final histological diagnosis after directed cervical biopsy. To test the level of agreement between the colposcopy and Gynocular, we calculated the percentage agreement and the κ statistic. We calculated the detection rates of cervical lesions of the Gynocular and a standard colposcope using biopsy results as criterion standards. All included patients also underwent a Pap smear. RESULTS: The level of agreement of Swede score between the Gynocular and colposcope was 70.1% and the κ statistic was 0.65 (p < .001). Biopsy identified 4 women (6.7%) with cervical intraepithelial neoplasia 1 (CIN 1) and 1 woman (1.7%) with CIN 2; 2 women (3.4%) had CIN 3, and 2 women had invasive cervical cancer (CIN 3+). Pap smear detected 2 women (3.1%) with CIN 1 but did not identify any high-grade cervical lesion. Cervicitis was present in 17 (27.4%) of the Pap smears and in 34 (57.6%) of the biopsies. CONCLUSIONS: The study shows that in visual inspection with acetic acid-positive women, a battery-driven, pocket-sized colposcope has a significant level of agreement with stationary colposcopy in assessing cervical lesions.

Risks of emergency cesarean section and fetal asphyxia after induction of labor in intrahepatic cholestasis of pregnancy: a hospital-based retrospective cohort study.

OBJECTIVES: Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy liver-specific disease. Induction of labor in gestational weeks 37-39 is commonly performed with the perspective to avoid the complication of stillbirth. We aimed to study whether this practice increases the risks of emergency cesarean section (CS) and fetal asphyxia. STUDY DESIGN: We assessed the risk of emergency CS and fetal asphyxia in ICP among women with spontaneous and induced onset of labor in comparison to women without ICP. We performed a hospital based retrospective cohort study with 25,870 singleton pregnancies, 333 with ICP (1.3%), of which 231 gave birth in weeks 37-39. Obstetric outcome was assessed through linkage of the Swedish Medical Birth Registry and a local obstetrical database based on the patient's medical files. MAIN OUTCOME MEASURE: Risk for emergency CS; fetal asphyxia and postpartum hemorrhage. RESULTS: The risk of emergency CS in ICP with spontaneous onset of labor (12.5%) did not differ from non ICP women with spontaneous onset of labor (9.3%; aOR, 1.33; 95% CI 0.60-2.96). When labor was induced, risk of emergency CS was significantly lower among women with ICP than among without ICP (aOR, 0.47; 95% CI 0.26-0.86). Exclusion of women with preeclampsia, gestational hypertension or diabetes mellitus did not alter the result. The risk for fetal asphyxia was not significantly associated with ICP status. CONCLUSION: Induction of labor in women with ICP gestational weeks 37-39 did not increase the risks of emergency CS or fetal asphyxia.

PP001. The vascular tree during pregnancy and at follow-up - A longitudinal study of maternal vascular function.

INTRODUCTION: Normal maternal vascular function and optimal cardiovascular adaptation to the increasing demands of pregnancy is a prerequisite for a successful outcome of pregnancy. How different levels of the vascular tree react and interact during pregnancy has not been fully investigated previously but may be determined by genetic as well as maternal, fetal and environmental factors. OBJECTIVE: To investigate how different levels of vascular function change during the course of pregnancy and relate these levels to each other. METHODS: Healthy non smoking women with singleton pregnancies and a viable embryo recorded at the ultrasound departments of UltraGyn Stockholm, Sweden were recruited. The following cardiovascular examinations were performed: examination of structural changes of the heart: Echocardiography of the heart with Doppler examination and tissue Doppler. Examination of macrocirculation, vessel structure and function plus endothelial function: Intima-media thickness of the common carotid artery, pulse wave velocity, central blood pressure and flow mediated vasodilation. Examination of microvascular function in the skin and endothelial function: total circulation of the skin and capillary flow in nails. The microcirculation before, during and after iontophoresis with nitroprussid and acetylcholine. The investigations were performed in gestational week 11-14, 22-24, 36 and 9 months post partum. RESULTS: In total 35 participants had a normal course of pregnancy. Curves of the development of the various cardiovascular variables will be presented according to gestational age and their place in the vascular tree. CONCLUSIONS: These curves will be used to investigate how various determinants such as blood pressure, fetal growth and body mass index, as well as fetal sex affects and are affected by cardiovascular function in pregnancy.

Induction of labor and the risk for emergency cesarean section in nulliparous and multiparous women.

OBJECTIVE: To assess the risk for emergency cesarean section among women in whom labor was induced in gestational week ≥41 and to evaluate if parity and mode of induction affected this association. DESIGN: Hospital-based retrospective cohort study. POPULATION: Singleton pregnancies delivered after ≥41 gestational weeks at Danderyd Hospital, Stockholm, Sweden, during 2002-2006. MATERIAL AND METHODS: Of 23 030 singleton pregnancies meeting the entry criteria, 881 were induced with a Bishop score of <7. Obstetric outcome was assessed through linkage with the Swedish Medical Birth Registry and a local obstetrical database containing information from patients' medical files. Results were adjusted for body mass index, age and the use of epidural analgesia. MAIN OUTCOME MEASURE: Risk for emergency cesarean section. RESULTS: Among women who were induced, the proportions delivered by emergency cesarean section were 42% for nulliparous and 14% for multiparous. Compared to spontaneous onset, this corresponded to a more than threefold increase in risk for nulliparous women (OR 3.34, 95%CI 2.77-4.04) and an almost twofold increase in risk for multiparous women (OR 1.94, 95%CI 1.24-3.02). There was no significant difference in risk for emergency cesarean section between the two methods of induction (PGE(2) and transcervical catheter). CONCLUSIONS: Compared to spontaneous onset of delivery, induction of labor is associated with an increased risk for emergency cesarean section both among nulliparous and multiparous women. When labor is induced, the high risk for emergency cesarean must be kept in mind.

Cesarean delivery and risk for postoperative adhesions and intestinal obstruction: a nested case-control study of the Swedish Medical Birth Registry.

OBJECTIVE: The objective of the study was to estimate the risk for postoperative adhesions and intestinal obstruction after cesarean delivery and to estimate whether the rate remains stable over time. STUDY DESIGN: Women who had the aforementioned diagnoses in the Swedish Hospital Discharge Registry were linked to the Swedish Medical Birth Registry. Women with diagnoses increasing the risk for adhesions were excluded. More than 900,000 women were investigated. Risks were calculated and were adjusted for age, parity, body mass index, and smoking. RESULTS: Women delivered by cesarean delivery had an increased risk of adhesions: adjusted odds ratio, 2.1 (95% confidence interval, 1.8-2.4) and intestinal obstruction: adjusted odds ratio, 2.0 (95% confidence interval, 1.7-2.4). The number needed to harm was 360. Multiple caesarean deliveries increased the risk of adhesions. The risk did not increase over time. CONCLUSION: The absolute risk of postoperative adhesions and intestinal obstruction after cesarean section are low but should be included when counseling women requesting cesarean delivery.