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Background Improved information about the evolution of fetal head rotation during labor is required. Ultrasound methods have the potential to provide reliable new knowledge about fetal head position. Objective The aim of the study was to describe fetal head rotation in women in spontaneous labor at term using ultrasound longitudinally throughout the active phase. Study Design This was a single center, prospective cohort study at Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland, from January 2016 to April 2018. Nulliparous women with a single fetus in cephalic presentation and spontaneous labor onset at ≥37 weeks’ gestation were eligible. Inclusion occurred when the active phase could be clinically established by labor ward staff. Cervical dilatation was clinically examined. Fetal head position and subsequent rotation were determined using both transabdominal and transperineal ultrasound. Occiput positions were marked on a clockface graph with 24 half-hour divisions and categorized into occiput anterior (≥10- and ≤2-o’clock positions), left occiput transverse (>2- and 8- and Results We followed the fetal head rotation relative to the initial position in the pelvis in 99 women, of whom 75 delivered spontaneously, 16 with instrumental assistance, and 8 needed cesarean delivery. At inclusion, the cervix was dilated 4 cm in 26 women, 5 cm in 30 women, and ≥6 cm in 43 women. Furthermore, 4 women were examined once, 93 women twice, 60 women 3 times, 47 women 4 times, 20 women 5 times, 15 women 6 times, and 3 women 8 times. Occiput posterior was the most frequent position at the first examination (52 of 99), but of those classified as posterior, most were at 4- or 8-o’clock position. Occiput posterior positions persisted in >50% of cases throughout the first stage of labor but were anterior in 53 of 80 women (66%) examined by and after full dilatation. The occiput position was anterior in 75% of cases at a head-perineum distance of ≤30 mm and in 73% of cases at an angle of progression of ≥125° (corresponding to a clinical station of +1). All initial occiput anterior (19), 77% of occiput posterior (40 of 52), and 93% of occiput transverse positions (26 of 28) were thereafter delivered in an occiput anterior position. In 6 cases, the fetal head had rotated over the 6-o’clock position from an occiput posterior or transverse position, resulting in a rotation of >180°. In addition, 6 of the 8 women ending with cesarean delivery had the fetus in occiput posterior position throughout the active phase of labor. Conclusion We investigated the rotation of the fetal head in the active phase of labor in nulliparous women in spontaneous labor at term, using ultrasound to provide accurate and objective results. The occiput posterior position was the most common fetal position throughout the active phase of the first stage of labor. Occiput anterior only became the most frequent position at full dilatation and after the head had descended below the midpelvic plane.

Endometriosis is a chronic condition causing menstrual pain, irregular bleeding and infertility among women. Although usually in the pelvis, it can manifest in atypical places. We describe a 39-year old woman with a previous endometriosis diagnosis who presented three times on the second menstrual day with dyspnea and chest pain. Imaging showed right-sided pneumothorax on all three occasions. Thoraco­scopy revealed endometriosis-like lesions. Histology was suggestive of endometriosis. After treatment with chemical pleurodesis and hormonal suppression she has remained symptom-free. Diagnosis should be obtained by concomitant thoraco- and laparoscopy with biopsies to verify the disease and give a basis for appropriate treatment.

Macrosomia and child obesity are growing health-care issues worldwide. The purpose of the study was to evaluate how extremely high or low birth weight affects metabolic markers evaluated in newborn screening. The study was register-based and included full-term singletons born in Iceland from 2009 to 2012 with newborn screening samples taken 72–96 h after birth. Three groups based on birth weight were compared: low birth weight (

To study the prevalence of pelvic floor dysfunction and related bother in primiparous women 6–10 weeks postpartum, comparing vaginal and cesarean delivery. Cross-sectional study of 721 mothers with singleton births in Reykjavik, Iceland, 2015 to 2017, using an electronic questionnaire. Information on urinary and anal incontinence, pelvic organ prolapse and sexual dysfunction with related bother (trouble, nuisance, worry, annoyance) was collected. Main outcome measures were prevalence of pelvic floor dysfunction and related bother. The overall prevalence of urinary and anal incontinence was 48% and 60%, respectively. Bother regarding urinary symptoms was experienced by 27% and for anal symptoms by 56%. Pelvic organ prolapse was noted by 29%, with less than half finding this bothersome. Fifty-five percent were sexually active, of whom 66% reported coital pain. Of all the women, 48% considered sexual issues bothersome. Urinary incontinence and pelvic organ prolapse were more prevalent in women who delivered vaginally compared to cesarean section, but no differences were observed for anal incontinence and coital pain. Compared to women with BMI 50th percentile was predictive for urgency incontinence after vaginal delivery (OR 1.53; 95% CI 1.05–2.21). Episiotomy predicted more anal incontinence (OR 2.19; 95% CI 1.30–3.67). No associations between maternal and delivery characteristics were found for pelvic floor dysfunction after cesarean section. Bothersome pelvic floor dysfunction symptoms are prevalent among first-time mothers in the immediate postpartum period.

AIMS To estimate potential differences in neonatal metabolomic profiles at birth and at the time of newborn screening by delivery mode. METHODS A prospective study at Women's Clinic at Landspitali-The National University Hospital of Iceland. Women having normal vaginal birth or elective caesarean section from November 2013 to April 2014 were offered participation. Blood samples from mothers before birth and umbilical cord at birth were collected and amino acids and acylcarnitines measured by tandem mass spectrometry. Results from the Newborn screening programme in Iceland were collected. Amino acids and acylcarnitines from different samples were compared by delivery mode. RESULTS Eighty three normal vaginal births and 32 elective caesarean sections were included. Mean differences at birth were higher for numerous amino acids, and some acylcarnitines in neonates born vaginally compared to elective caesarean section. Maternal blood samples and newborn screening results showed small differences that lost significance after correction for multiple testing. Many amino acids and some acylcarnitines were numerically higher in cord blood compared to maternal. Many amino acids and most acylcarnitines were numerically higher in newborn screening results compared to cord blood. CONCLUSION We observed transient yet distinct differences in metabolomic profiles between neonates by delivery mode.

Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia., Studies to identify maternal variants associated with preeclampsia have been limited by sample size. Here, the authors meta-analyze eight GWAS of 9,515 preeclamptic women, identifying five variants associated with preeclampsia and showing that genetic predisposition to hypertension is a major risk factor for preeclampsia.

ObjectivePrevious studies have suggested that female athletes might be at higher risk of experiencing complications such as caesarean sections and perineal tears during labour than non-athletes. Our aim was to study delivery outcomes, including emergency caesarean section rates, length of the first and second stages of labour and severe perineal tears, in first-time pregnant elite athletes compared with non-athletes.MethodsThis is a retrospective case–control study comparing birth outcomes of primiparous female elite athletes engaging in high-impact and low-impact sports compared with non-athletic controls. The athletes had prior to birth competed at a national team level or equivalent. Participant characteristics and frequency of training for at least 3 years before a first pregnancy were collected via a self-administered questionnaire. Information on delivery outcome was retrieved from the Icelandic Medical Birth Registry.ResultsIn total, 248 participated, 118 controls, 41 low-impact and 89 high-impact elite athletes. No significant differences were found between the groups with regard to incidence of emergency caesarean section or length of the first and second stages of labour. The incidence of third-degree to fourth-degree perineal tears was significantly higher (23.7%) among low-impact athletes than in the high-impact group (5.1%, p=0.01), but no significant differences were seen when the athletes were compared with the controls (12%; p=0.09 for low-impact and p=0.12 for high-impact athletes).ConclusionParticipation in competitive sports at the elite level was not related to adverse delivery outcome, including length of labour, the need for caesarean section during delivery and severe perineal tears.

Identifying predictive factors for a normal outcome at admission in the labor ward would be of value for planning labor care, timing interventions, and preventing labor dystocia. Clinical assessments of fetal head station and position at the start of labor have some predictive value, but the value of ultrasound methods for this purpose has not been investigated. Studies using transperineal ultrasound before labor onset show possibilities of using these methods to predict outcomes.This study aimed to investigate whether ultrasound measurements during the first examination in the active phase of labor were associated with the duration of labor phases and the need for operative delivery.This was a secondary analysis of a prospective cohort study at Landspitali University Hospital, Reykjavík, Iceland. Nulliparous women at ≥37 weeks' gestation with a single fetus in cephalic presentation and in active spontaneous labor were eligible for the study. The recruitment period was from January 2016 to April 2018. Women were examined by a midwife on admission and included in the study if they were in active labor, which was defined as regular contractions with a fully effaced cervix, dilatation of ≥4 cm. An ultrasound examination was performed by a separate examiner within 15 minutes; both examiners were blinded to the other's results. Transabdominal and transperineal ultrasound examinations were used to assess fetal head position, cervical dilatation, and fetal head station, expressed as head-perineum distance and angle of progression. Duration of labor was estimated as the hazard ratio for spontaneous delivery using Kaplan-Meier curves and Cox regression analysis. The hazard ratios were adjusted for maternal age and body mass index. The associations between study parameters and mode of delivery were evaluated using receiver operating characteristic curves.Median times to spontaneous delivery were 490 minutes for a head-perineum distance of ≤45 mm and 682 minutes for a head-perineum distance of45 mm (log-rank test, P=.009; adjusted hazard ratio for a shorter head-perineum distance, 1.47 [95% confidence interval, 0.83-2.60]). The median durations were 506 minutes for an angle of progression of ≥93° and 732 minutes for an angle of progression of93° (log-rank test, P=.008; adjusted hazard ratio, 2.07 [95% confidence interval, 1.15-3.72]). The median times to delivery were 506 minutes for nonocciput posterior positions and 677 minutes for occiput posterior positions (log-rank test, P=.07; adjusted hazard ratio, 1.52 [95% confidence interval, 0.96-2.38]) Median times to delivery were 429 minutes for a dilatation of ≥6 cm and 704 minutes for a dilatation of 4 to 5 cm (log-rank test, P=.002; adjusted hazard ratio, 3.11 [95% confidence interval, 1.68-5.77]). Overall, there were 75 spontaneous deliveries; among those deliveries, 16 were instrumental vaginal deliveries (1 forceps delivery and 15 ventouse deliveries), and 8 were cesarean deliveries. Head-perineum distance and angle of progression were associated with a spontaneous delivery with area under the receiver operating characteristic curves of 0.68 (95% confidence interval, 0.55-0.80) and 0.67 (95% confidence interval, 0.55-0.80), respectively. Ultrasound measurement of cervical dilatation or position at inclusion was not significantly associated with spontaneous delivery.Ultrasound examinations showed that fetal head station and cervical dilatation were associated with the duration of labor; however, measurements of fetal head station were the variables best associated with operative deliveries.

Background Ultrasound measurements offer objective and reproducible methods to measure the fetal head station. Before these methods can be applied to assess labor progression, the fetal head descent needs to be evaluated longitudinally in well-defined populations and compared with the existing data derived from clinical examinations. Objective This study aimed to use ultrasound measurements to describe the fetal head descent longitudinally as labor progressed through the active phase in nulliparous women with spontaneous onset of labor. Study Design This was a single center, prospective cohort study at the Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland, from January 2016 to April 2018. Nulliparous women with a single fetus in cephalic presentation and spontaneous labor onset at a gestational age of ≥37 weeks, were eligible. Participant inclusion occurred during admission for women with an established active phase of labor or at the start of the active phase for women admitted during the latent phase. The active phase was defined as an effaced cervix dilated to at least 4 cm in women with regular contractions. According to the clinical protocol, vaginal examinations were done at entry and subsequently throughout labor, paired each time with a transperineal ultrasound examination by a separate examiner, with both examiners being blinded to the other’s results. The measurements used to assess the fetal head station were the head-perineum distance and angle of progression. Cervical dilatation was examined clinically. Results The study population comprised 99 women. The labor patterns for the head-perineum distance, angle of progression, and cervical dilatation differentiated the participants into 75 with spontaneous deliveries, 16 with instrumental vaginal deliveries, and 8 cesarean deliveries. At the inclusion stage, the cervix was dilated 4 cm in 26 of the women, 5 cm in 30 of the women, and ≥6 cm in 43 women. One cesarean and 1 ventouse delivery were performed for fetal distress, whereas the remaining cesarean deliveries were conducted because of a failure to progress. The total number of examinations conducted throughout the study was 345, with an average of 3.6 per woman. The ultrasound-measured fetal head station both at the first and last examination were associated with the delivery mode and remaining time of labor. In spontaneous deliveries, rapid head descent started around 4 hours before birth, the descent being more gradual in instrumental deliveries and absent in cesarean deliveries. A head-perineum distance of 30 mm and angle of progression of 125° separately predicted delivery within 3.0 hours (95% confidence interval, 2.5–3.8 hours and 2.4–3.7 hours, respectively) in women delivering vaginally. Although the head-perineum distance and angle of progression are independent methods, both methods gave similar mirror image patterns. The fetal head station at the first examination was highest for the fetuses in occiput posterior position, but the pattern of rapid descent was similar for all initial positions in spontaneously delivering women. Oxytocin augmentation was used in 41% of women; in these labors a slower descent was noted. Descent was only slightly slower in the 62% of women who received epidural analgesia. A nonlinear relationship was observed between the fetal head station and dilatation. Conclusion We have established the ultrasound-measured descent patterns for nulliparous women in spontaneous labor. The patterns resemble previously published patterns based on clinical vaginal examinations. The ultrasound-measured fetal head station was associated with the delivery mode and remaining time of labor.

Introduction Sexual violence against children is a hidden problem. Medical examination and evaluation is needed to search for possible injuries, exclude infections, procure legal evidence and ensure the child´s welfare. We assessed medical evaluations done at Landspitali University Hospital and in the Reykjavik Children's House, a specialized clinic for childhood abuse cases. Material and methods Retrospective descriptive analysis was performed on the standardized medical examinations. Age, sex, waiting time from reported violence until examination and recorded aberrant external genitalia findings were noted, and classified by the medically--oriented Adams system. Offence severity stages were assigned. Results Medical examination cases numbered 224 for 220 girls aged 1-17 years. Records were available on 218 standarized examinations among girls; 201 were adequate (92%). Most were conducted within a month (medium waiting-time 28 days; range 1-166). Hymenal changes were in 24 cases possibly associated with sexual violence, including 21 in a girl not sexually active. Two girls had human papillomavirus warts (1%) and one chlamydial infection (0.5%). Medical examination was normal in 85% (165/193) of girls who were not sexually active; 24 had possibly experienced sexual violence and four results were uncertain/controversial. For 71 offence severity was serious. Conclusion Most examinations were conducted on prepubertal girls, were not a matter of urgency and showed normal results. Possible relation to sexual violence was described for one in eight. Infections were rare. When child sexual abuse is suspected, care with methodology and procedures is needed, both for elective and acute medical examinations. Key words: Violence, child sexual abuse, children, external genitalia, injuries, severity grading. Correspondence: Ebba Margret Magnusdottir, ebbamag@landspitali.is.

INTRODUCTION Nutrition in pregnancy may affect growth, development and health of the child in the short and long term. We aimed to assess diet and nutrient intake among pregnant women in the capital area and evaluate differences in dietary intake between women who were overweight/obese and normal weight before pregnancy. MATERIAL AND METHODS Pregnant women aged 18-40 years (n=183) living in the capital area kept four day weighed food records to assess diet and nutrient intake in the 19th-24th week of pregnancy (n=98 with body mass index (BMI)

Introduction Physical activity (PA) is recommended as part of therapy for patients with impaired glucose tolerance. Whether such recommendations are also justified for pregnant women is less well established. We investigated the association between PA and glucose tolerance in pregnancy. Material and methods A non-selective sample of 217 pregnant women was recruited at a routine 20 week ultrasound examination. Participants answered the International Physical Activity Questionnaire (IPAQ) about frequency, intensity and duration of daily physical activity in the past 7 days and underwent oral glucose tolerance testing (OGTT) between 24 and 28 weeks. A subset of 72 overweight/obese pregnant women wore a pedometer for 1 week with assessment of IPAQ score and pedometric correlations to this. Results Of the sample, 177 attended for OGTT; 51% were overweight or obese. The mean (SD) fasting glucose was 4.5 (0.4) mmol/L, and 12% had gestational diabetes mellitus. Only one-third engaged in vigorous PA. After adjustment for pre-pregnancy BMI, age and parity, those engaging in vigorous PA had significantly lower fasting glucose levels (by 0.15 mmol/L, 95% CI 0.03-0.27) compared with those not vigorously active. This decrease was similar in both normal and overweight/obese women. There were fewer cases of gestational diabetes (p = 0.03) among the vigorously active women (3/56; 5%) than among those who were not active (19/121; 16%). No association with glucose tolerance was observed for physical activity of moderate intensity. Conclusions Only vigorous physical activity appears beneficial with respect to maternal glucose tolerance, both among normal, overweight and obese women.

Background Pelvic floor dysfunction, including urinary and anal incontinence, is a common postpartum complaint and likely to reduce quality of life. Objectives To study the effects of individualized physical therapist-guided pelvic floor muscle training in the early postpartum period on urinary and anal incontinence and related bother, as well as pelvic floor muscle strength and endurance. Study design Assessor-blinded parallel randomized controlled trial evaluating effects of pelvic floor muscle training by a physical therapist on the rate of urinary and/or anal leakage (primary outcomes), while related bother and muscle strength and endurance in the pelvic floor were secondary outcomes. Between 2016-2017 primiparous women giving birth at Landspitali University Hospital in Reykjavik, Iceland were screened for eligibilty 6-10 weeks after childbirth. Of those identified as urinary incontinent 95 were invited to participate of whom 84 agreed. The intervention, starting at ∼9 weeks postpartum consisted of 12 weekly sessions with a physical therapist after which the main outcomes were assessed (endpoint, ∼6 months postpartum). Additional follow-up was conducted at ∼12 months postpartum. The control group received no instructions after the initial assessment. Fisher´s exact test was used to test differences in the proportion of women with urinary and anal incontinence between intervention and control groups, while independent sample t-tests were used for mean differences in muscle strength and endurance. Significance levels were set as α=0.05. Results Forty-one and 43 women were randomized to the intervention and control groups, respectively. Three and one participants withdrew from these respective groups. Measurement variables and main delivery outcomes were not different at recruitment. At the endpoint, urinary incontinence was less frequent in the intervention group with 21 (57%) still symptomatic compared to 31 (82%) of the controls (P=0.03), as was bladder-related bother with 10 (27%) in the intervention vs. 23 (60%) in the control group, P=0.005. Anal incontinence was not influenced by pelvic floor muscle training (P=0.33), nor was bowel-related bother (P=0.82). The mean differences between groups in measured pelvic floor muscle strength changes at endpoint was 5 hPa (95%CI 2-8; P=0.003), and for pelvic floor muscle endurance changes, 50 hPa/sec (95%CI 23-77; P=0.001), both in favor of the intervention group. The mean between-group differences for anal sphincter strength changes was 10 hPa (95%CI 2-18; P=0.01), and for anal sphincter endurance changes 95 hPa/sec (95%CI 16-173; P=0.02), both in favor of the intervention. At the follow-up visit, 12 months postpartum, no differences were observed between the groups regarding rates of urinary and anal incontinence, nor related bother. Pelvic floor- and anal muscle strength and endurance favoring the intervention group were maintained. Conclusions Postpartum pelvic floor mucle training decreased the rate of urinary incontinence and related bother 6 months postpartum and increased muscle strength and endurance.

We thank the individuals who participated in the study and whose contribution made this work possible. We acknowledge the Icelandic Cancer Registry for assistance in the ascertainment of the cancer patients. T.R., B.G., P.S., B.V.H., G.T, and K.S. designed the study and interpreted the results. A.S, A.T., E.A.H., K.K., O.I., V.G., R.T.G., R.A., J.G.J., and K.O. carried out the subject ascertainment, recruitment, and collection of clinical data. U.S., V.S., S.N.S., J.G., G.A.A., A.O., F.Z., G.H., R.P.K., O.B.D., G.M., V.T., F.W.A., and U.T. collected, processed, and analyzed the genotype and phenotype data. O.A.S. performed the functional annotations. A.I., M.L.F., L.S., J.K.S., G.S., D.F.G., B.G., and B.V.H., performed the statistical and bioinformatics analyses. T.R., B.G., O.A.S, G.T., and K.S., drafted the manuscript. All authors contributed to the final version of the paper., Uterine leiomyomas are common benign tumors of the myometrium. We performed a meta-analysis of two genome-wide association studies of leiomyoma in European women (16,595 cases and 523,330 controls), uncovering 21 variants at 16 loci that associate with the disease. Five variants were previously reported to confer risk of various malignant or benign tumors (rs78378222 in TP53, rs10069690 in TERT, rs1800057 and rs1801516 in ATM, and rs7907606 at OBFC1) and four signals are located at established risk loci for hormone-related traits (endometriosis and breast cancer) at 1q36.12 (CDC42/WNT4), 2p25.1 (GREB1), 20p12.3 (MCM8), and 6q26.2 (SYNE1/ESR1). Polygenic score for leiomyoma, computed using UKB data, is significantly correlated with risk of cancer in the Icelandic population. Functional annotation suggests that the non-coding risk variants affect multiple genes, including ESR1. Our results provide insights into the genetic background of leiomyoma that are shared by other benign and malignant tumors and highlight the role of hormones in leiomyoma growth., This research has been conducted using the UK Biobank Resource under Application Number ‘24711’.

BACKGROUND Obstetric anal sphincter injuries lead frequently to short- and long-term consequences for the mother, including perineal pain, genital prolapse, and sexual problems. The aim of the study was to evaluate whether the implementation of an intervention program in the second stage of labor involving altered perineal support techniques reduced severe perineal trauma. METHODS All women reaching the second stage of labor and giving birth vaginally to singleton babies at Landspitali University Hospital (comprising 76% of births in Iceland in 2013) were enrolled in a cohort study. Data were recorded retrospectively for 2008-2010 and prospectively in 2012-2014, for a total of 16 336 births. During 2011, an intervention program was implemented, involving all midwives and obstetricians working in the labor wards. Two professionals assessed and agreed on classification of every perineal tear. RESULTS The prevalence of obstetric anal sphincter injuries decreased from 5.9% to 3.7% after the implementation (P

Introduction Despite the seriousness of the event, maternal deaths are substantially underreported. There is often a missed opportunity to learn from such tragedies. The aim of the study was to identify maternal deaths in the five Nordic countries, to classify causes of death based on internationally acknowledged criteria, and to identify areas that would benefit from further teaching, training or research to possibly reduce the number of maternal deaths. Material and methods We present data for the years 2005–2013. National audit groups collected data by linkage of registers and direct reporting from hospitals. Each case was then assessed to determine the cause of death, and level of care provided. Potential improvements to care were evaluated. Results We registered 168 maternal deaths, 90 direct and 78 indirect cases. The maternal mortality ratio was 7.2/100 000 live births ranging from 6.8 to 8.1 between the countries. Cardiac disease (n = 29) was the most frequent cause of death, followed by preeclampsia (n = 24), thromboembolism (n = 20) and suicide (n = 20). Improvements to care which could potentially have made a difference to the outcome were identified in one-third of the deaths, i.e. in as many as 60% of preeclamptic, 45% of thromboembolic, and 32% of the deaths from cardiac disease. Conclusion Direct deaths exceeded indirect maternal deaths in the Nordic countries. To reduce maternal deaths, increased efforts to better implement existing clinical guidelines seem warranted, particularly for preeclampsia, thromboembolism and cardiac disease. More knowledge is also needed about what contributes to suicidal maternal deaths.

Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown. Here we perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17,045 endometriosis cases and 191,596 controls. In addition to replicating previously reported loci, we identify five novel loci significantly associated with endometriosis risk (P, We acknowledge all the study participants in 11 individual endometriosis studies that provided an opportunity for the current study. We also thank many hospital directors and staff, gynaecologists, general practitioners and pathology services in Australia who provided assistance with confirmation of diagnoses. We would like to thank the research participants and employees of 23andMe for making this work possible. We thank the subjects of the Icelandic deCODE study for their participation. We thank research staff and clinicians for providing diagnostic confirmation for the OX data set. We would like to express our gratitude to the staff and members of the Biobank Japan and Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences for their outstanding assistance. The QIMR study was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia (241,944, 339,462, 389,927, 389,875, 389,891, 389,892, 389,938, 443,036, 442,915, 442,981, 496,610, 496,739, 552,485, 552,498, 1,026,033 and 1,050,208), the Cooperative Research Centre for Discovery of Genes for Common Human Diseases (CRC), Cerylid Biosciences (Melbourne) and donations from N. Hawkins and S. Hawkins. Analyses of the QIMRHCS and OX GWAS were supported by the Wellcome Trust (WT084766/Z/08/Z) and makes use of WTCCC2 control data generated by the Wellcome Trust Case-Control Consortium (awards 076113 and 085475). The iPSYCH study was funded by The Lundbeck Foundation, Denmark (R102-A9118, R155-2014-1724 ), and the research has been conducted using the Danish National Biobank resource supported by the Novo Nordisk Foundation. A full list of the investigators who contributed to the generation of these data is available from http://www.wtccc.org.uk. D.R.N. was supported in part by the NHMRC Fellowship (613674) and ARC Future Fellowship (FT0991022) schemes. E.G.H. (631096) and G.W.M. (339446, 619667) were supported by the NHMRC Fellowships Scheme. S.M. is supported by an Australian Research Council Future Fellowship. A.P.M. was supported by a Wellcome Trust Senior Research Fellowship (award WT098017). N.R. was supported by funding from the Medical Research Council UK (MR/K011480/1). This study was funded by the BioBank Japan project, which is supported by the Ministry of Education, Culture, Sports, Sciences and Technology of Japanese government.

Objective To investigate associations between mode of delivery and subsequent reproductive outcomes. Design Cohort study. Population Women with term singleton live births from 1987 to 2009. Setting Denmark, birth registration data. Methods Women with a first singleton delivery after 37 weeks were followed until the end of 2010, from a first birth to include subsequent live births. We used Cox's proportional hazards model stratified by parity to compare the likelihood for subsequent delivery according to mode of delivery at first and later births, estimating maternal age effects and lag time to next delivery. Main outcome measure Likelihood of a subsequent live-born child by previous delivery mode. Results We identified 642 052 women with a first delivery. Compared with women with a non-instrumental vaginal delivery, delivering a child by elective cesarean section implied a 23% (95% CI 0.76–0.787) decreased likelihood for subsequent delivery. Emergency cesarean section meant 16% fewer (95% CI 0.84–0.85), and vaginal instrumental delivery 4% fewer subsequent deliveries (95% CI 0.95–0.96). Hazard ratios were largely unchanged after controlling for parity and year of birth. Small age-trends were seen, with hazard ratios affected by maternal age at birth. Delivery mode at first birth affected marginally the time lag until next birth. Conclusions Fecundity, measured as likelihood of a successive live-born child, varied with mode of delivery at the first and also subsequent births. A first or later delivery by cesarean section implied decreased likelihood of subsequent delivery compared with women with a first vaginal birth.

INTRODUCTION Amniocentesis and chorionic villus sampling (CVS) are methods for fetal chromosomal diagnosis. Pregnant women aged ≥35 years have been offered amniocentesis in Iceland for over 35 years. The main testing indication was maternal age until 1998, when universal early screening was introduced. We examined outcome and fetal loss following amniocentesis and CVS in singleton and twin pregnancies, age distribution changes, reasons for the procedures and fetal karyotype diagnoses. MATERIAL AND METHODS Retrospective quantitative study on women who had amniocentesis and CVS (n=2323) in the Prenatal Diagnosis Unit at Landspitali University Hospital during 1998-2007. Unit files and individual case and maternity records were used to retrieve information on the indications and on maternal age, type of procedure, outome of pregnancy, and the fetal karyotype. RESULTS The number of procedures was substantially reduced from over 500 to just over 100 per year, with a proportional shift to CVS. Procedure-related fetal loss was 22/2323 (0.9%), with no significant difference between amniocentesis (0.8%) and CVS (1.3%). The difference decreased in the latter half of the study period to 0.7% and 0.8%, respectively. Age-related reasons decreased from 81.2% to 30.8%. CONCLUSION The fetal loss incidence rates indicated that amniocentesis and CVS have the same safety level as elsewhere. Complications were uncommon. With CVS fetal screening was moved to an earlier time in pregnancy. Early screening has changed the maternal age profile and is available to all women on request. The information obtained can be used to improve service information.

INTRODUCTION Ectopic pregnancy can be life-threatening. Its treatment has changed radically during the last two decades. The study objective was to evaluate incidence and treatment of ectopic pregnancy in the Icelandic population during the decade 2000-2009. MATERIAL AND METHODS Information was collected about all diagnosed cases, place and method of treatment and admissions. The annual incidence was calculated with reference to number of pregnancies (n/1000), number of women aged 15-44 years (n/10 000) and by 5-year age groups, comparing the periods 2000-2004 and 2005-2009. RESULTS The number of ectopic pregnancies during these 10 years was 836, or 444 during the years 2000-2004 and 392 during 2005-2009. The average annual incidence was 15.6/1000 pregnancies and 12.9/10 000 women. There was an annual incidence reduction from 17.3 to 14.1/1000 pregnancies (p

INTRODUCTION Type 1 diabetes has wide-ranging effects for expectant mothers and their unborn children. Optimal blood sugar control minimizes complications for both. We assessed maternal and neonatal outcome in relation to glycemic control. MATERIAL AND METHODS Retrospective evaluation of pregnancies among type 1 diabetic women in Iceland during 1999-2010, with information collected from maternity and newborn records on disease severity, HbA1c values before and during pregnancy, delivery mode and complications. RESULTS There were 93 pregnancies among 68 women (47% primigravid). Mean age was 29 years and mean time from diabetes diagnosis 16 years (median 19, range 35 years (p=0.02). Delivery was induced in 40% and the cesarean section rate was 65%. Mean gestation was 37+2 weeks. There were two stillbirths. Preterm deliveries were 28%. Congenital anomalies affected 9% of newborns (mostly cardiac). One-third of newborns developed diabetic fetopathy, one-quarter jaundice, both associated with worse maternal bloodsugars. CONCLUSIONS Most women with type 1 diabetes improved blood sugar control during pregnancy, which became good or acceptable by the last trimester by HbA1c values. Cesarean section was over three times more frequent than in the general population. Neonatal complications and congenital anomalies were also more common. To minimize complications improved control of bloodsugar is needed before and throughout pregnancy.

BACKGROUND: New studies about the influence of hormonal contraception on the risk of venous thromboembolism (VTE) have been published. AIM: To evaluate new epidemiological data and to propose clinical consequences. DESIGN: A literature survey. METHODS: Studies assessing the risk of specific types of hormonal contraception were evaluated compared and set into a clinical perspective. RESULTS: The majority of newer studies have demonstrated a threefold increased risk of VTE in current users of medium- and low-dose combined oral contraceptives (COCs) with norethisterone levonorgestrel (LNG) or norgestimate compared with non-users. The same studies have demonstrated a sixfold increased risk of VTE in users of combined pills with desogestrel gestodene drospirenone or cyproteroneacetate and in users of the contraceptive vaginal ring compared with non-users. The rate ratio of VTE between users of COCs with newer progestogens compared with users of COCs with LNG was 1.5-2.8 in seven studies and 1.0 in two studies. Progestogen-only contraception did not confer an increased risk of VTE in any study. The incidence rate of VTE in non-pregnant women aged 15-49 years using non-hormonal contraception is three per 10 000 years. CONCLUSIONS: For women starting on hormonal contraception we recommend medium- or low-dose combined pills with norethisterone LNG or norgestimate as first-choice preparations. For the many women who are users of COCs with newer progestogens although the absolute risk of VTE is low a change to combined pills with norethisterone LNG or norgestimate may halve their risk of VTE. Finally we recommend COCs with 20 mug estrogen combined with the older progestogens to be launched in the Scandinavian countries. Women at an increased risk of VTE should consider progestogen-only contraception or non-hormonal contraception. (c) 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica(c) 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

Background: We present the case of very early onset pre-eclampsia, possibly aggravated by liquorice consumption. Case: An 18-year-old healthy primigravida presented with high blood pressure and proteinuria at 18 weeks gestation. She had a strong family history of pre-eclampsia and was consuming considerable amounts of liquorice. A diagnosis of severe pre-eclampsia/hemolysis, elevated liver enzymes, and low platelet count was confirmed. The pregnancy was terminated. Extensive investigation ruled out underlying diseases and autopsy revealed a normal fetus. In three consequtive pregnancies, she developed milder forms of pre-eclampsia. Conclusion: In healthy women with a familial/genetic susceptibility for pre-eclampsia, liquorice consumption may aggravate the course of the disease.

Objective The purpose of this study was to investigate the recurrence of hypertensive disorders in pregnancy with regard to the type of disorder, the onset of hypertension, and the modulating effect of overweight and weight gain between pregnancies. Study design Maternity records from 896 parous women with hypertensive disorders in pregnancy in the first pregnancy were reviewed to reclassify disease status and calculate odds ratios for recurrence. Results Recurrence of hypertensive disorders in pregnancy occurred in 58% to 94% of second pregnancies, depending on first pregnancy disorder. Overweight (odds ratio, 1.82) and weight gain (odds ratio, 2.20) were related to recurrence among women with gestational hypertension. Early hypertension (≤34 weeks of gestation) increased the recurrence risk for women with gestational hypertension (odds ratio, 1.85) and preeclampsia (odds ratio, 3.42). Conclusion Recurrence of hypertensive disorders in pregnancy is common, but not specified by type of disorder in first pregnancy. Overweight and weight gain between pregnancies are associated with recurrent hypertensive disorders in pregnancy in women with gestational hypertension. Early onset of hypertension is a risk factor, independent of body weight.

Gestational diabetes mellitus (GDM) is associated with negative health effects for mother and child. The aim was to investigate the association between maternal dietary patterns and GDM.Prospective observational study including 168 pregnant women aged 18-40 years, recruited at routine 20-week ultrasound. All participants kept a 4-day weighed food record following recruitment (commencement: gestational weeks 19-24). Principal component analysis was used to extract dietary patterns from 29 food groups. A Healthy Eating Index (HEI) was constructed. All women underwent an oral glucose tolerance test in weeks 23-28.One clear dietary pattern (Eigenvalue 2.4) was extracted with positive factor loadings for seafood; eggs; vegetables; fruits and berries; vegetable oils; nuts and seeds; pasta; breakfast cereals; and coffee, tea and cocoa powder, and negative factor loadings for soft drinks and French fries. This pattern was labeled a prudent dietary pattern. Explained variance was 8.2%. The prevalence of GDM was 2.3% among women of normal weight before pregnancy (n=86) and 18.3% among overweight/obese women (n=82). The prudent dietary pattern was associated with lower risk of GDM (OR: 0.54; 95% CI: 0.30, 0.98). When adjusting for age, parity, prepregnancy weight, energy intake, weekly weight gain and total metabolic equivalent of task the association remained (OR: 0.36; 95% CI: 0.14, 0.94). Similar results were found when only including overweight or obese women (OR: 0.31; 95% CI: 0.13, 0.75).Adhering to a prudent dietary pattern in pregnancy was clearly associated with lower risk of GDM, especially among women already at higher risk because of overweight/obesity before pregnancy.

Objective To investigate quantitative aberrations involving p53 copy numbers in eutopic endometrial and endometriotic tissue from two populations. Design Comparative analysis of normal and diseased tissue. Setting Tissue specimens collected in Iceland and USA. Patient(s) Subjects with moderate/severe endometriosis (Iceland, n=26; USA, n=45). Paraffin-embedded tissue from 19 matched Icelandic cases and seven unaffected controls. American cases were fresh surgical tissue from 17 matched cases and 28 unaffected controls. DNA isolation and real-time polymerase chain reaction (PCR) with TaqMan assay were performed. Main Outcome Measure(s) The frequency of p53 loss and/or gain based on quantitative differences for copy numbers of p53 located on chromosome (17p) and GAPDH on a control locus (chromosome 12p). Result(s) Among American cases, significant p53 gain (n = 13) or loss (n = 4) was observed in 17 of 21 cases. In Icelandic cases this was not seen to the same degree. Mean normalized p53 values were 3.46 and 1.16 copies per reaction, respectively. Significant differences were observed between normalized p53 in the control blood and affected tissue for the American and Icelandic cases compared to standard GAPDH control but not in normal Icelandic and American endometrium. Conclusion(s) The results continue to support a role for nonrandom somatic p53 locus alterations in the pathogenesis of late or severe-stage endometriosis. Differences between Icelandic and American subjects have implications for generalization of genome-wide approaches.

Background. Iceland is often considered very similar to the other Nordic countries. The purpose of this study was to explore trends in teenage fertility abortion and pregnancy rates in Iceland compare these trends with corresponding rates in Denmark Finland Norway and Sweden during the period 1976-99 and to evaluate similarities and dissimilarities. Methods. The study is based on data about fertility abortion and pregnancy rates obtained from the Icelandic and Nordic national population and abortion registers for the age group 15-19 years. Results. Teenage fertility and pregnancy rates in the five Nordic countries declined over the study period by 57-67% and 31-50% respectively and in Iceland they remained significantly higher than in the Nordic countries. In 1999 almost every other teenage pregnancy in Iceland (45.9/1000) resulted in a childbirth (24.4/1000). Regional fertility rates were highest in the countryside. While the abortion rate has been declining in the four Nordic countries by 20-41% they have concurrently been rising in Iceland by 133% (9.4/1000 in 1976-80 21.9/1000 in 1996-99) and are presently higher than in the other Nordic countries. Regionally abortion rates in Iceland were highest in the Capital area. Conclusions. The teenage pregnancy rate is higher in Iceland than in the other Nordic countries. This may be explained by cultural norms in Icelands society regarding childbearing early initiation of sexual intercourse more limited sex education and less effective delivery and use of contraceptive methods. There is a need to promote sexual and reproductive health to young people in Iceland by combining diverse preventive approaches. (authors)

OBJECTIVE: To investigate the relation between gestational weight gain in women of normal prepregnant weight and complications during pregnancy and delivery in a population with high gestational weight gain and birth weight. METHODS: Healthy women (n = 615) of normal weight before pregnancy (body mass index 19.5–25.5 kg/m2) were randomly selected. Maternity records gave information on age, height, prepregnant weight, gestational weight gain, parity, smoking, gestational hypertension and diabetes, preeclampsia, delivery complications, and infants’ birth size and health. RESULTS: The mean weight gain in pregnancy was 16.8 ± 4.9 kg (mean ± standard deviation). A total of 26.4% of the women had complications, either in pregnancy (9.1%) or delivery (17.3%). Women gaining weight according to the recommendation of the Institute of Medicine (11.5–16.0 kg) had lower frequency of pregnancy-delivery complications than women gaining more than 20.0 kg (P = .017), but did not differ significantly from those gaining 16–20 kg (P > .05). When dividing weight gain in pregnancy into quintiles, a relative risk of 2.69 (95% confidence interval 1.01, 7.18, P = .048) was found for complications in pregnancy in the fourth quintile (17.9–20.8 kg), using the second quintile as reference (12.5–15.5 kg). The mean birth weight was 3778 ± 496 g. A low weight gain in pregnancy (less than 11.5 kg) was associated with an increased frequency of infants weighing less than 3500 g at birth (P < .01). CONCLUSION: A gestational weight gain of 11.5–16.0 kg (Institute of Medicine recommendation) for women of normal prepregnant weight is related to the lowest risk for pregnancy-delivery complications. In the population studied, the upper limit might be higher (up to 18 kg), and low weight gain should be avoided to optimize birth outcome.

Objective To evaluate the effects of desogestrel 75μg/day, as a progestogen-only pill compared with a copper-bearing intrauterine contraceptive device (IUCD) on lactation and to study the safety of both treatments in mothers and children. Transfer of etonogestrel to breast milk was studied in a subgroup of desogestrel users. The children were to be followed up until 2.5 years of age. Design An open, non-randomised, group-comparative study in lactating women. Setting University Hospital, Reykjavik, Iceland. Participants A total of 83 lactating women; 42 received desogestrel and 41 had an IUCD inserted for seven consecutive treatment cycles of 28 days. Methods Evaluation visits were planned at baseline and at the end of treatment cycles 1, 4 and 7. The amount of breast milk was determined by weighing the infants before and after feeding, at baseline and after treatment cycles 1 and 4. Milk samples were obtained at the same time for constituent measurements. Safety was studied by structured medical examinations and by recording adverse experiences in mothers and children. Results There were no significant differences between the desogestrel and IUCD groups in composition and quantity of breast milk nor in growth and development of the children followed up to the age of 2.5 years. In the desogestrel group a slightly higher incidence of mild adverse experiences of a hormonal nature was reported among both mothers and infants. Of the children 82% were followed until 1.5 years of age and 50% until 2.5 years. Conclusion The use of desogestrel 75μg/day did not change the amount and composition of breast milk nor did it affect growth and development of the breastfed children. It appears to be a safe and effective contraceptive method for lactating women

Introduction Maternal death, during pregnancy or within 42 and 365 days from the end of pregnancy, was evaluated for a small high-income nation with comprehensive healthcare. Material and methods Cases were identified using record linkage by running national census information on all deaths of women aged 15–49 years during 1985–2009 against the national birth register and computerized hospital admission files for pregnancy-related diagnoses as well as actual case records where needed. Death certificates and hospital records were reviewed. Results Thirty deaths were identified; 26 at ≥22 weeks (= birth) and four earlier in pregnancy. For 107 871 deliveries, the overall mortality was 27.8/100 000. There were five direct deaths (4.6/100 000 deliveries), five indirect deaths (4.6/100 000 deliveries) and 19 coincidental deaths (17.6/100 000 deliveries). Using WHO criteria (direct and indirect in pregnancy or at ≤42 days postpartum) the ratio was 5.6/100 000 deliveries (95% confidence interval 1.1–10.1) and 5.5/100 000 live births (maternal mortality ratio, based on six deaths). Direct deaths were caused by sepsis, severe preeclampsia and choriocarcinoma, indirect by suicide, pre-existing cardiac and diabetic illness. No woman died of postpartum hemorrhage, anesthesia or ectopic pregnancy. Suboptimal care occurred. Conclusion Maternal mortality in Iceland over a 25-year period up to the end of year 2010 was low, between 5 and 6/100 000 births. A comprehensive national healthcare system with accessible antenatal care in a society with good general living conditions and universal education probably contributed to this.

Ectopic pregnancy can be life-threatening. Its treatment has changed radically during the last two decades. The study objective was to evaluate incidence and treatment of ectopic pregnancy in the Icelandic population during the decade 2000-2009.Information was collected about all diagnosed cases, place and method of treatment and admissions. The annual incidence was calculated with reference to number of pregnancies (n/1000), number of women aged 15-44 years (n/10 000) and by 5-year age groups, comparing the periods 2000-2004 and 2005-2009.The number of ectopic pregnancies during these 10 years was 836, or 444 during the years 2000-2004 and 392 during 2005-2009. The average annual incidence was 15.6/1000 pregnancies and 12.9/10 000 women. There was an annual incidence reduction from 17.3 to 14.1/1000 pregnancies (p0.01) and 14.1 to 11.7/10 000 women (p0.01). Surgery was the primary treatment for 94.9% of women, methotrexate in 3.2% and expectant management in 1.9%. Surgical management decreased from 98.0% to 91.3% between 5-year periods as medical treatment increased (0.4% to 6.4%; p0.0001). The proportion of laparoscopic procedures increased from 80.5% to 91.1% (p0.0001). In the university referral hospital this changed from 91.3% to 98.1% (p0.001) and in rural hospitals from 44.0% to 69.3% (p0.001). Mean hospital stay after open surgery was 3.2 days, but 0.9 days after laparoscopy.The incidence reduction of ectopic pregnancy is comparable to the development in neighbouring countries. Management has changed with increased use of laparoscopic surgery, medical and expectant treatment.

Pre-eclampsia is a common and serious disease and a major cause of maternal and infant mortality. Antenatal care systems world-wide screen for signs of the disease such as hypertension and proteinuria. Unlike most other human disorders it impacts two individuals, the mother and the child, both of whom can be severely affected. The pathophysiology of the disorder is incompletely understood, but familial clustering of the disease is apparent. Here we report the results of a genome-wide screen of Icelandic families representing 343 affected women. Including those patients with non-proteinuric pre-eclampsia (gestational hypertension), proteinuric pre-eclampsia and eclampsia, we detected a significant locus on 2p13 with a lod score of 4.70 (single point P < 3.49 x 10(-6)). This is the first reported locus for pre-eclampsia meeting the criteria for genome-wide significance.