Gunilla Ajne

Targeted Routine Antenatal Anti-D Prophylaxis in the Prevention of RhD Immunisation - Outcome of a New Antenatal Screening and Prevention Program

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.

Procedure-Related Complications and Perinatal Outcome after Intrauterine Transfusions in Red Cell Alloimmunization in Stockholm

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.

A Population-based Cohort Study of Pregnancy Outcomes Among Women With Primary Sclerosing Cholangitis

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.

Endothelin Converting Enzyme (ECE) Activity in Normal Pregnancy and Preeclampsia

Objective: 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. Study design: 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. Results: In normal pregnancy endothelin‐1 concentrations at 38 weeks and postpartum were increased by 30% (p < 0.01) and 50% (p < 0.001), 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; p < 0.001). Likewise, endothelin‐converting‐enzyme activity was higher in the preeclampsia group (222 ± 15 vs. 172 ± 8 pmol ET/ml/h; p < 0.01). This difference remained at six weeks postpartum. Conclusion: 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.

Traction force during vacuum extraction: a prospective observational study.

To investigate the traction force employed during vacuum extractions.

Single versus pairwise interpretation of cardiotochography, a comparative study from six Swedish delivery units

OBJECTIVE The aim of the study was to evaluate whether interpreting CTG pairwise brings about a higher level of correctly classified CTG recordings in a non-selected population of midwives and physicians. STUDY DESIGN A comparative study. SETTING Five delivery units in Stockholm and one delivery unit in Uppsala, with 1589, 3740, 3908, 4539, 6438, and 7331 deliveries in 2011, respectively. SUBJECTS 536 midwives and physicians classified one randomly selected CTG recording individually followed by a pairwise classification. The pairs consisted of two midwives (119 pairs) or one midwife and one physician (149 pairs), a total of 268 pairs. MAIN OUTCOME MEASURE The proportion of individually correctly classified CTG recordings versus the proportion of pairwise correctly classified CTG recordings. RESULTS The proportion of individually correctly classified CTGs was 75% and the proportion of pairwise correctly classified CTGs was 80% (difference 5%, p = 0.12). CONCLUSIONS There was no statistically significant difference when CTGs were classified pairwise compared to individual classifications. The proportion of individually correctly classified CTGs was high (75%). There were differences in the proportion of correctly classified CTG recordings between the delivery units, indicating potential areas of improvement.

Identification of pregnancies at increased risk of brachial plexus birth palsy - the construction of a weighted risk score

Abstract 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 Malmö, Sweden. A risk score was constructed for all women who had received routine municipal maternal health care at Skåne 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 ≤1 (2/3 of the population). Conclusion: Our findings indicate that it is possible to identify women at increased risk of having a child with BPBP by using variables observable in advance of delivery.

Predictive value of traction force measurement in vacuum extraction : Development of a multivariate prognostic model

Objective To enable early prediction of strong traction force vacuum extraction. Design Observational cohort. Setting Karolinska University Hospital delivery ward, tertiary unit. Population and sample size Term mid and low metal cup vacuum extraction deliveries June 2012—February 2015, n = 277. Methods Traction forces during vacuum extraction were collected prospectively using an intelligent handle. Levels of traction force were analysed pairwise by subjective category strong versus non-strong extraction, in order to define an objective predictive value for strong extraction. Statistical analysis A logistic regression model based on the shrinkage and selection method lasso was used to identify the predictive capacity of the different traction force variables. Predictors Total (time force integral, Newton minutes) and peak traction (Newton) force in the first to third pull; difference in traction force between the second and first pull, as well as the third and first pull respectively. Accumulated traction force at the second and third pull. Outcome Subjectively categorized extraction as strong versus non-strong. Results The prevalence of strong extraction was 26%. Prediction including the first and second pull: AUC 0,85 (CI 0,80–0,90); specificity 0,76; sensitivity 0,87; PPV 0,56; NPV 0,94. Prediction including the first to third pull: AUC 0,86 (CI 0,80–0,91); specificity 0,87; sensitivity 0,70; PPV 0,65; NPV 0,89. Conclusion Traction force measurement during vacuum extraction can help exclude strong category extraction from the second pull. From the third pull, two-thirds of strong extractions can be predicted.

Authors' reply re: Traction force during vacuum extraction: a prospective observational study.

Sir, We refer to the article ‘Traction force during vacuum extraction: a prospective observational study’ published in BJOG. This article provides a good resource on the amount of force employed during vacuum extraction deliveries, and on developing a vacuum extractor that measures the traction force, which can be a useful addition for the safety of instrumental deliveries. This paper has failed to comment on some relevant aspects of traction force applied during vacuum deliveries, however, including the relationship of traction force with the correct application of the cup. Firstly, they have not provided any information on the measure of traction force exerted in occipito-transverse fetal head position, and there seems to be no clear explanation why this group was not considered for the study. The rotational vacuum deliveries are an important group and any study to investigate traction force employed during vacuum delivery will be less validated if this group is excluded. As seen in this study, the traction force required in occipitoposterior positions is higher than that required in occipito-anterior fetal head positions, and it would be reasonable to presume that the same will be true in occipito-transverse positions where rotation and correction of asynclitism is required for successful vacuum extraction. Secondly, even though there is no consensus on the safe level of traction force, experts consider that a traction force of no more than 14 kg is required for most vacuum-assisted deliveries, whereas this study used a maximum safe traction force level of 216 N, corresponding to 22 kg. Given that neonatal complications, including hypoxic ischaemic encephalopathy (HIE) and intracranial haemorrhage, have been linked with increased traction force, further explanation of the safe limits of traction force is warranted. Surprisingly, this study has also made no attempt to describe the correct application of the vacuum cup, which directly determines the success of vacuum extraction consequent to the degree of traction force applied. The importance of the flexion point, which produces traction in the flexing median direction during vacuum deliveries, is pivotal to a successful outcome, and any deviation in application is likely to increase the risk of neonatal complications or failure of vacuum delivery. The para-median flexing or de-flexing application of the cup instead produces asynclitism, and has been associated with increased neonatal complications and failures. It would be imperative to know the position of cup application where excessive traction force was required or where vacuum extraction failed, and this should have been described in the study.&

Contents Vol. 30, 2011

R. Achiron, Tel Hashomer N.S. Adzick, Philadelphia, Pa. L. Allan, London A.A. Baschat, Baltimore, Md. K.J. Blakemore, Baltimore, Md. T.-H. Bui, Stockholm F.A. Chervenak, New York, N.Y. T. Chiba, Tokyo F. Crispi, Barcelona J.E. De Lia, Milwaukee, Wisc. J.A. Deprest, Leuven G.C. Di Renzo, Perugia J.W. Dudenhausen, Berlin N.M. Fisk, Brisbane, Qld. A.W. Flake, Philadelphia, Pa. U. Gembruch, Bonn M.R. Harrison, San Francisco, Calif. J.C. Hobbins, Denver, Colo. L.K. Hornberger, San Francisco, Calif. E.R.M. Jauniaux, London M.P. Johnson, Philadelphia, Pa. C. Jorgensen, Copenhagen J.-M. Jouannic, Paris P.M. Kyle, London O. Lapaire, Basel S. Lipitz, Tel-Hashomer G. Malinger, Holon G. Mari, Detroit, Mich. M. Martinez-Ferro, Buenos Aires K.J. Moise, Houston, Tex. K.H. Nicolaides, London D. Oepkes, Leiden L. Otaño, Buenos Aires Z. Papp, Budapest R. Quintero, Miami G. Ryan, Toronto J. Rychik, Philadelphia, Pa. H. Sago, Tokyo W. Sepulveda, Santiago P. Stone, Auckland D.V. Surbek, Bern B.J. Trudinger, Westmead, N.S.W. J.M.G. van Vugt, Amsterdam Y. Ville, Paris Clinical Advances and Basic Research