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Background and objective Routine antenatal anti-D prophylaxis (RAADP) to RhD-negative women is most often administered in gestational age (GA) 28-30 weeks with the next anti-D dose administered postpartum. The aim of this study was to analyse the proportion of RhD-negative women where RAADP is not detectable at term and in a pilot study to investigate whether RAADP administered in GA 28 and 38 results in detectable levels at term, post-term and post-delivery. Materials and methods In a retrospective analysis, 4280 RhD-negative women carrying an RHD positive fetus were included and the proportion with a negative antibody screen at delivery was determined. In the second part, 39 pregnancies were included prospectively, a second dose of RAADP was administered in GA 38 weeks, and anti-D was quantified before the second dose and then weekly for 5 weeks. Results In the retrospective analysis, 20·5% (856/4280) with RAADP administered in GA 28 were negative in routine antibody screening at delivery. In the small prospective study, 18% (7/39) had a negative antibody screen and 26% (10/39) had levels below 0·005 IU/ml, in the quantification assay, in GA 38. Anti-D prophylaxis administered in GA 38 showed detectable levels of anti-D up to 30 days post-delivery, with concentration at delivery 0·060 ± 0·034 IU/ml (mean ± SD). Conclusion Approximately 20% of the RhD-negative women show non-detectable levels of anti-D at term. A second dose of RAADP at GA 38 results in stable concentrations of anti-D at term, post-term and post-delivery, but with large interindividual variation.

Background Low and mid station vacuum assisted deliveries (VAD) are delicate manual procedures that entail a high degree of subjectivity from the operator and are associated with adverse neonatal outcome. Little has been done to improve the procedure, including the technical development, traction force and the possibility of objective documentation. We aimed to explore if a digital handle with instant haptic feedback on traction force would reduce the neonatal risk during low or mid station VAD. Methods A two centre, randomised superiority trial at Karolinska University Hospital, Sweden, 2016–2018. Cases were randomised bedside to either a conventional or a digital handle attached to a Bird metal cup (50 mm, 80 kPa). The digital handle measured applied force including an instant notification by vibration when high levels of traction force were predicted according to a predefined algorithm. Primary outcome was a composite of hypoxic ischaemic encephalopathy, intracranial haemorrhage, seizures, death and/or subgaleal hematoma. Three hundred eighty low and mid VAD in each group were estimated to decrease primary outcome from six to 2 %. Results After 2 years, an interim analyse was undertaken. Meeting the inclusion criteria, 567 vacuum extractions were randomized to the use of a digital handle (n = 296) or a conventional handle (n = 271). Primary outcome did not differ between the two groups: (2.7% digital handle vs 2.6% conventional handle). The incidence of primary outcome differed significantly between the two delivery wards (4% vs 0.9%, p Conclusions The incidence of primary outcome was lower than estimated and the study was underpowered. However, the difference between the two delivery wards might reflect varying degree of experience of the technical equipment. An objective documentation of the extraction procedure is an attractive alternative in respect to safety and clinical training. To demonstrate improved safety, a multicentre study is required to reach an adequate cohort. This was beyond the scope of the study. Trial registration ClinicalTrials.gov NCT03071783, March 1, 2017, retrospectively registered.

Introduction Anti-D alloimmunization is the most common cause of severe hemolytic disease of the fetus and newborn (HDFN). The management of pregnancies affected by less frequent red blood cell (RBC) antibodies poses a challenge to clinicians, and perinatal outcomes are less well described. This study aimed to describe the frequency of clinically significant RBC antibodies in our pregnant population and analyze the risk of prenatal and postnatal treatment for HDFN in relation to our national risk classification system and management guidelines. Material and methods A retrospective cohort study in the population of all alloimmunized singleton pregnancies in the Stockholm region 1990-2016. Descriptive summaries of different RBC antibodies and pregnancy outcomes were presented, the risks of intrauterine blood transfusion (IUT) and neonatal treatment for HDFN were estimated by type of antibodies. Results Of the 1724 alloimmunized pregnancies, 1079 (63%) were at risk of HDFN and constituted our study cohort. Anti-D was detected in 492 (46%) pregnancies, followed by anti-E in 161 (15%), and anti-c in 128 (12%). Eighty-seven (8%) pregnancies had IUT, with the highest risk in pregnancies affected by anti-D combined with other antibodies. The maximum titer recorded before IUT was 64 or above, except for two pregnancies affected by anti-c, for which the maximum titers were 8 and 16. For the 942 (95%) live-born neonates from 992 alloimmunized pregnancies without IUT, the median gestational age at birth was 38+5 weeks compared with 35+5 weeks for those who had IUT. Neonatal treatment was most common in the anti-D alone and anti-D combined groups, with 136 (57%) and 21 (44%), respectively, treated with phototherapy and 35 (15%) and 9 (20%) receiving exchange transfusions, respectively. For pregnancies complicated by moderate- and low-risk antibodies, phototherapy was less frequent (32 [36%] and 21 [19%]) and exchange transfusion was rare (5 [6%] and 3 [3%]). Conclusions Anti-D, especially in combination with other antibodies, presents the highest risk of severe HDFN. The classification of less frequent and less well-known RBC antibodies into risk groups can help clinicians in assessing the risk of HDFN and counseling alloimmunized pregnant women regarding the risk of prenatal and postnatal treatments.

Eclampsia with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is a rare complication of pregnancy. HELLP syndrome may occur up to a week postpartum in women with eclampsia. CASE REPORT: We report a case of liver transplantation with the organ procured from a pregnant (gestation week 28) female donor who suffered brain death after cerebellar hemorrhage owing to eclampsia. Liver function tests were normal at the time of liver procurement. The liver graft was matched to a 62-year-old man with primary sclerosing cholangitis. On day 7 after an uneventful transplantation, the recipient presented with increased aminotransferases and severe thrombocytopenia. The recipient also developed hypertension and hyperthermia and a clinical picture of HELLP syndrome. The patient underwent emergency liver retransplantation on day 12 after the first transplantation. Intraoperatively, massive necrosis of the liver graft with diffuse subcapsular hematomas was seen. CONCLUSIONS: It appears that in our case, HELLP syndrome was transferred to and occurred in a male recipient. Eclampsia in the donor without overt HELLP syndrome may persist and be transferred by liver graft, developing into HELLP syndrome even in a male recipient. Therefore, liver grafts from female donors with eclampsia should be used with caution. Emergency retransplantation may be necessary.

Background and aim: Transient elastography can detect liver fibrosis by estimation of liver stiffness. Results may be falsely high when blood flow to the liver is increased, such as during ...

INTRODUCTION Traction force is a possible risk factor for adverse neonatal outcome in vacuum extraction delivery, but the knowledge is scarce and further investigation is needed. Our hypothesis was that high-level traction force increases the risk of admission to the neonatal intensive care unit. MATERIAL AND METHODS The study was a hospital-based prospective cohort study on low- and mid-vacuum extractions at the labor and delivery ward, Karolinska University Hospital, Huddinge, Sweden. Traction forces were measured in 331 women. An electronical handle was used to measure and register traction force. The main exposure variable was high-level traction force (≥75th percentile) during the first three pulls and the primary outcome was admission to the neonatal intensive care unit. Logistic regression was used to estimate the adjusted risk. RESULTS Among the exposed, 14/84 (16.7%) were admitted to neonatal intensive care, and among the unexposed 10/247 (4%). The crude odds ratio (OR) of admission to the neonatal intensive care unit when exposed to high-level traction force was 4.7, and the adjusted (birthweight, gestational length, cup detachment, number of pulls, duration, duration >15 minutes, mid-cavity fetal head station, failed extraction, indication and parity) OR was 2.85 (95% confidence interval [CI] 1.09-7.48). No significant effect was seen in Apgar scores

The decrease in pH in monochorionic (MC) second twin may exceed that of dichorionic (DC) second twin during vaginal twin delivery. The aim of this study was to investigate the effect of chorionicity on the umbilical artery pH of the second twin in relation to increased twin-to-twin delivery time interval (DTI) from 30 weeks of gestation. A hospital based cohort of all twin deliveries after 30 completed weeks of gestation with the first twin delivered vaginally between 2007 and 2012 in four delivery units in Stockholm county was conducted. The changes of umbilical pH in MC twins compared to DC twins in relation to twin-to-twin DTI was studied using linear regression. The predictors for acidosis (pH ≤ 7.10) in the second twin were studied by logistic regression. The cohort included 681 DC and 186 MC twin pairs. There was a correlation between the umbilical pH and the twin-to-twin DTI but independent of the chorionicity, the pH decreased in average by 0.0012 units/min (p < .001). Twin-to twin DTI was a predictor for acidosis of the second twin (p < .01). IMPACT STATEMENT What is already known on this subject? Vaginal twin deliveries are a major obstetrical challenge because of the increased risk for the second twin after the delivery of the first twin, and are suggested to increase among premature second twins. Previous studies report a continuous decline in the pH of the second twin during the second stage of labour, with an increased risk for acidosis (pH < 7.10) and Apgar scores

Background The optimal strategy to monitor RhD-immunized pregnancies is not evident. Whether a quantitative analysis of anti-D antibodies adds valuable information to anti-D titre is unclear. The aim of this study was to evaluate the relevance of anti-D quantification in routine monitoring of RhD-immunized pregnancies. Materials and methods In a retrospective study, 64 consecutive pregnancies in 61 immunized women with anti-D titre ≥128 at any time during pregnancy were included. According to routine, at titre ≥128, anti-D quantification was performed by flow cytometry and the peak systolic velocity in the middle cerebral artery was measured by ultrasound. Decisions for treatment with intrauterine blood transfusion were based on increased peak systolic velocity in the middle cerebral artery. Results Increasing anti-D concentrations correlated well to increasing anti-D titres, but at each titre value, there was a large interindividual variation, in the determined anti-D concentration. Intrauterine transfusions were initiated in 35 pregnancies according to algorithms based on ultrasound measurements, at anti-D concentrations of 2·4-619 IU/ml and titre 128-16 000. Sixty pregnancies resulted in a live-born child, three in miscarriage and one in termination of pregnancy. During the perinatal care in the neonatal intensive care unit, thirty-one of the neonates were treated with blood exchange transfusions and/or red cell transfusions and 47 were treated with phototherapy. Conclusion Anti-D quantification does not add further information compared to anti-D titre, in defining a critical level to start monitoring RhD-immunized pregnancies with Doppler ultrasound.

Objective To investigate the traction force employed during vacuum extractions. Design Observational cross-sectional study. Setting Obstetric Department, Karolinska University Hospital, Sweden, and the Swedish National Congress of Obstetrics and Gynaecology, 2013. Population Two hundred women with vacuum extraction at term and 130 obstetricians participating in a simulated setting. Methods In a normal clinical setting, we used a specially adapted device to measure and record the force used to undertake vacuum extraction. In a subsequent part of the study, the force employed for vacuum extraction by a group of obstetricians in a fictive setting was estimated and objectively measured. Main outcome measures Applied force during vacuum extraction in relation to the estimated level of difficulty in the delivery; perinatal diagnoses of asphyxia or head trauma; estimated force compared with objectively measured force employed in the fictive setting. Results The median (minimum–maximum) peak forces for minimum, average and excessive vacuum extraction in the clinical setting were 176 N (5–360 N), 225 N (115–436 N), and 241 N (164–452 N), respectively. In 34% of cases a force in excess of 216 N was employed. There was no correlation between the umbilical arterial pH at delivery and the traction force employed during extraction. Four cases of mild hypoxic ischaemic encephalopathy were observed, three of which were associated with a delivery whereby excessive traction force was employed during the vacuum extraction. In the fictive setting, the actual exerted force was twice the quantitative estimation. The measured forces in the clinical setting were four times higher than that estimated in the fictive setting. Conclusions Higher than expected levels of traction force were used for vacuum extraction delivery. As obstetricians tend to underestimate the force applied during vacuum extraction, objective measurement with instantaneous feedback may be valuable in raising awareness.

Hemolytic disease of the fetus and newborn (HDFN) owing to anti-U has rarely been reported. U is part of the MNS system. M and N glycoproteins are located on glycophorin A (GPA); S and s antigens are on glycophorin B (GPB). Individuals who lack GPB are S– and s– and also lack U. The U– phenotype occurs almost exclusively in the African population and has a very low frequency (0.25%). Anti-U is of immunoglobulin G class and can cause hemolytic transfusion reaction and HDFN. In this report we present the use of a noninvasive method to detect anemia in the fetus and the subsequent use of intrauterine transfusion (IUT) with blood of a very rare phenotype. For the first time, we used deglycerolized and 3-week-old red blood cell units for IUT without signs of adverse reactions and with the expected effect on the hemoglobin value. We conclude that this transfusion strategy could be applied safely. Immunohematology 2013;29:51– 54.

Introduction: We present a review of all cases of intravascular transfusions in red cell alloimmunization over a time span of 20 years in Stockholm. The aim of the study is to compare our results with published results from larger centers and to identify areas that can be further improved. Material and Methods: A retrospective cohort study was conducted of all women treated with intrauterine transfusions due to erythrocyte immunization in our hospital between June 1990 and June 2010. Primary outcome variables were fetal and neonatal survival, procedure-related complications and gestational age at delivery. Results: A total of 284 intrauterine transfusions were performed in 84 pregnancies, with an overall survival rate of 91.8%. Procedure-related and fatal complications occurred in the present study in 4.9 and 1.4% of fetuses or neonates, respectively. Procedure-related complications were significantly more common in free-loop transfusions than in transfusions in the intrahepatic part of the umbilical vein (OR: 5.4, p = 0.025). There was no significant difference between the intrahepatic and the placental cord insertion route (p = 0.83). Gestational age at first transfusion was significantly associated with an increased risk of a procedure-related complication (OR: 0.8, p = 0.019). Of the live-born infants, 24% of the neonates were born before gestational week 34. Discussion: Our study confirms previous studies demonstrating favorable results with intravascular transfusions.

Objective The aim of this study was to evaluate the role of the ETA receptor and nitric oxide (NO) in the regulation of uteroplacental and renal blood flow in pregnant rats. Study design Regional blood flows were measured by the microsphere technique in pregnant Sprague-Dawley rats (term 23 days). Blood flow was measured before and after ETA receptor blockade (BQ-123, 1 mg/kg) at gestational day (GD) 19 or 21 (n=8 and n=9, respectively). In 2 additional groups blood flow was measured before and after NO synthase inhibition (L-NAME 2 μg/min) at GD 19 or 21 (n=10 in each group). Results BQ-123 significantly increased placental and myometrial blood flows by almost 80% and 35%, respectively, at both gestational ages. BQ-123 did not alter renal blood flow. No effect on placental or myometrial blood flow was observed after L-NAME infusion, neither at GD 19 nor GD 21. Renal blood flow decreased by nearly 35% in both groups after L-NAME. Conclusion There is an important role for endogenous ET in the regulation of uteroplacental blood flow in the rat. NO contributes to a significant vasodilatation in the renal vasculature; however, NO appears not to be involved in the maintenance of uteroplacental blood flow in the awake pregnant rat.

Advancing pregnancy is characterized by a ten-fold increase in uterine blood flow and a 50 per cent increase in renal blood flow. To evaluate the involvement of endogenous endothelin (ET) in these haemodynamic changes the effect of bosentan, an ETA/B receptor antagonist, on uteroplacental and renal blood flow was studied in awake pregnant Sprague-Dawley rats. Regional blood flows were measured using microsphere technique immediately prior to and 30 min after bosentan administration (20 mg/kg i.v.). Four groups of animals (term: 23 days) were included: bosentan was administered to ten rats at gestation day (GD) 19 and nine at GD 20-21. In addition, four rats at GD 19 and five animals at GD 20-21 received saline and served as control groups. Basal placental blood flow increased significantly from 19 days' gestation to 20-21 days. Basal myometrial blood flow did not change with gestational age. At gestation day 19 bosentan increased placental and myometrial blood flow significantly (80 per cent and 43 per cent, respectively, P

Objective To estimate the incidence of RhD immunisation after implementation of first trimester non-invasive fetal RHD screening to select only RhD negative women carrying RHD positive fetuses for routine antenatal anti-D prophylaxis (RAADP). Materials and Methods We present a population-based prospective observational cohort study with historic controls including all maternity care centres and delivery hospitals in the Stockholm region, Sweden. All RhD negative pregnant women were screened for fetal RHD genotype in the first trimester of pregnancy. Anti-D immunoglobulin (250–300 µg) was administered intramuscularly in gestational week 28–30 to participants with RHD positive fetuses. Main outcome measure was the incidence of RhD immunisation developing during or after pregnancy. Results During the study period 9380 RhD negative women gave birth in Stockholm. Non-invasive fetal RHD genotyping using cell-free fetal DNA in maternal plasma was performed in 8374 pregnancies of which 5104 (61%) were RHD positive and 3270 (39%) RHD negative. In 4590 pregnancies with an RHD positive test the women received antenatal anti-D prophylaxis. The incidence of RhD immunisation in the study cohort was 0.26 percent (24/9380) (95% CI 0.15–0.36%) compared to 0.46 percent (86/18546) (95% CI 0.37 to 0.56%) in the reference cohort. The risk ratio (RR) for sensitisation was 0.55 (95% CI 0.35 to 0.87) and the risk reduction was statistically significant (p = 0.009). The absolute risk difference was 0.20 percent, corresponding to a number needed to treat (NNT) of 500. Conclusions Using first trimester non-invasive antenatal screening for fetal RHD to target routine antenatal anti-D prophylaxis selectively to RhD negative women with RHD positive fetuses significantly reduces the incidence of new RhD immunisation. The risk reduction is comparable to that reported in studies evaluating the outcome of non selective RAADP to all RhD negative women. The cost-effectiveness of this targeted approach remains to be studied.

Objective: Since it is difficult to identify women at increased risk of fetal brachial plexus birth palsy (BPBP) during labor and delivery, we aimed to construct and validate a risk score. Methods: A retrospective case-control study was undertaken in 2001 and 2006 in an urban context in Malmo, Sweden. A risk score was constructed for all women who had received routine municipal maternal health care at Skane University Hospital (n = 10 459). The model was validated among all pregnant women with BPBP and controls in Sweden between 2006 and 2007. Results: The likelihood of BPBP increased as the risk score rose: 3.1% of the women studied had a risk score >= 5, including 32.1% of the BPBP cases, where the risk showed a 38-fold increase, as compared to those with a risk score

Background & Aims Studies of primary sclerosing cholangitis (PSC) and pregnancy outcomes have been limited in size and have been inadequate to rule out excess risks. We examined pregnancy outcomes among women with PSC. Methods Women with PSC were identified from inpatient and hospital-based outpatient data in the Swedish National Patient Register. Through linkage with the Medical Birth Register, we identified 229 singleton births, from 1987 through 2009, to women with PSC before delivery. These were compared with 2,304,863 births to women without a diagnosis of PSC. We used logistic regression, adjusted for maternal age, smoking, education, parity, and year of birth, to calculate adjusted prevalence odds ratios (aPORs) for adverse pregnancy outcomes. Results Maternal PSC was associated with a 3.63-fold increase in preterm birth (95% confidence interval [CI] for aPOR, 2.35–5.61) as well as an increased risk of cesarean section (aPOR, 2.18; 95% CI, 1.50–3.17). We found no increased risk based on analyses of the 5-minute Apgar score, small for gestational age, stillbirths, or neonatal deaths. Maternal PSC was not a risk factor for congenital abnormalities (aPOR, 1.12; 95% CI, 0.56–2.22). Stratification by inflammatory bowel disease status did not affect the risk estimates more than marginally. Conclusions Maternal PSC is associated with both preterm birth and cesarean section but not with congenital malformation or other adverse outcomes of pregnancy. Pregnancy should not be discouraged in women with PSC.

Enhanced production of endothelin-1, due to endothelial cell dysfunction has been considered to be the cause of increased plasma levels of endothelin-1 in preeclampsia. The present study was aimed at analyzing endothelin-converting-enzyme activity, (which reflect the production rate of endothelin-1 (ET-1) from big endothelin-1 (big ET-1)), big endothelin-1, and endothelin-1 concentrations from women with preeclampsia compared to normal pregnant women. Moreover, we analyzed plasma levels of these substances longitudinally throughout normal pregnancy.Twenty-nine pregnant healthy women were recruited to the study. Blood samples were obtained at 18, 28, and 38 weeks gestation and six weeks postpartum. Twenty-seven women with preeclampsia were included. Blood samples were taken at diagnosis (average 35 weeks gestation; range 27-39 weeks) and six weeks postpartum. Endothelin-1 was analyzed by enzyme linked immunoassay (ELISA) and big-ET-1 by radioimmunoassay (RIA). Endothelin-converting-enzyme activity was measured using big endothelin-1 as a substrate and thiorphan as an inhibitor of serum neutral endopeptidase. The amount of endothelin-1 generated during one hour was measured by RIA. Mean +/- SEM is given.In normal pregnancy endothelin-1 concentrations at 38 weeks and postpartum were increased by 30% (p0.01) and 50% (p0.001), respectively compared with the second trimester values. Endothelin-converting-enzyme activity did not change. At diagnosis endothelin-1 was higher in women with preeclampsia than in the controls at 38 weeks (0.96 +/- 0.07 vs. 0.64 +/- 0.06 pmol/L; p0.001). Likewise, endothelin-converting-enzyme activity was higher in the preeclampsia group (222 +/- 15 vs. 172 +/- 8 pmol ET/ml/h; p0.01). This difference remained at six weeks postpartum.Our findings imply enhanced ET-1 production in preeclampsia. The elevated endothelin-converting-enzyme activity postpartum may indicate an inherent endothelial dysfunction predisposing to preeclampsia or that preeclampsia may cause irreversible changes in endothelial function.