Publications by authors named "Luigi Raio"

100 Publications

Informal coercion during childbirth: risk factors and prevalence estimates from a nationwide survey of women in Switzerland.

BMC Pregnancy Childbirth 2021 May 10;21(1):369. Epub 2021 May 10.

Department of Health Professions, Applied Research & Development in Midwifery, Bern University of Applied Sciences, Murtenstrasse 10, 3008, Bern, Switzerland.

Background: In many countries, the increase in facility births is accompanied by a high rate of obstetric interventions. Lower birthrates or elevated risk factors such as women's higher age at childbirth and an increased need for control and security cannot entirely explain this rise in obstetric interventions. Another possible factor is that women are coerced to agree to interventions, but the prevalence of coercive interventions in Switzerland is unknown.

Methods: In a nationwide cross-sectional online survey, we assessed the prevalence of informal coercion during childbirth, women's satisfaction with childbirth, and the prevalence of women at risk of postpartum depression. Women aged 18 years or older who had given birth in Switzerland within the previous 12 months were recruited online through Facebook ads or through various offline channels. We used multivariable logistic regression to estimate the risk ratios associated with multiple individual and contextual factors.

Results: In total, 6054 women completed the questionnaire (a dropout rate of 16.2%). An estimated 26.7% of women experienced some form of informal coercion during childbirth. As compared to vaginal delivery, cesarean section (CS) and instrumental vaginal birth were associated with an increased risk of informal coercion (planned CS risk ratio [RR]: 1.52, 95% confidence interval [1.18,1.96]; unplanned CS RR: 1.92 [1.61,2.28]; emergency CS RR: 2.10 [1.71,2.58]; instrumental vaginal birth RR: 2.17 [1.85,2.55]). Additionally, migrant women (RR: 1.45 [1.26,1.66]) and women for whom a self-determined vaginal birth was more important (RR: 1.15 [1.06,1.24]) more often reported informal coercion. Emergency cesarean section (RR: 1.32 [1.08,1.62]), being transferred to hospital (RR: 1.33 [1.11,1.60]), and experiencing informal coercion (RR: 1.35 [1.19,1.54]) were all associated with a higher risk of postpartum depression. Finally, women who had a non-instrumental vaginal birth reported higher satisfaction with childbirth while women who experienced informal coercion reported lower satisfaction.

Conclusions: One in four women experience informal coercion during childbirth, and this experience is associated with a higher risk of postpartum depression and lower satisfaction with childbirth. To prevent traumatic after-effects, health care professionals should make every effort to prevent informal coercion and to ensure sensitive aftercare for all new mothers.
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http://dx.doi.org/10.1186/s12884-021-03826-1DOI Listing
May 2021

Effect of the IADPSG screening strategy for Gestational Diabetes on perinatal outcomes in Switzerland.

Diabetes Res Clin Pract 2021 Apr 22:108830. Epub 2021 Apr 22.

Department of Health Professions, Bern University of Applied Sciences. Murtenstrasse 10. 3008 Bern. Switzerland.

Aims: To evaluate the impact adoption of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria on prevalence of gestational diabetes mellitus (GDM) and risks of perinatal outcomes.

Methods: Retrospectively, 155'103 women screened with selective two step criteria in Switzerland in period 1 (2005-2010) were compared to 170'427 women screened with IADPSG criteria in period 2 (2012-2017). GDM prevalence over time was established and multivariable regression used to assess variation in risks for GDM related events and perinatal outcomes.

Results: GDM prevalence increased steadily over both study periods from 1.8% to 9.0%. A risk reduction of GDM-related events was shown only for women with one or two risk factors for GDM present (0.93 (0.90,0.97), 0.90 (0.83,0.96)). The comparison of perinatal outcomes between the two study periods revealed a significant lower risk for newborns large for gestational age (LGA) (RR 0.93 (0.91-0.95)), pre-term delivery (RR 0.94 (0.92-0.97)) and neonatal hypoglycemia (RR 0.83 (0.77-0.90)) in period 2.

Conclusion: The introduction of the IADPSG criteria for the screening of GDM increased prevalence by threefold with no substantial improvements in GDM related events for women without risk factors but reduced the risks for LGA, neonatal hypoglycemia and preterm birth.
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http://dx.doi.org/10.1016/j.diabres.2021.108830DOI Listing
April 2021

Double inferior vena cava in a monochorionic twin pregnancy with selective fetal growth restriction.

BMJ Case Rep 2021 Mar 10;14(3). Epub 2021 Mar 10.

Department for Obstetrics and Gynecology, Inselspital Bern Universitätsklinik für Frauenheilkunde, Bern, BE, Switzerland.

Congenital anomalies of the infrarenal inferior vena cava (IVC) are well described in adult life, however, little information exists on their associations in fetal life. Here, we describe a case of a monochorionic diamniotic (MCDA) twin pregnancy complicated by selective fetal growth restriction (sFGR) with an incidental finding of a double IVC in one child. In fetal life, variants of the infrarenal IVC are strongly associated with heart defects, which might suggest haemodynamic alterations or genetic causes, even more so in our case with MCDA twins complicated by sFGR.
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http://dx.doi.org/10.1136/bcr-2020-240379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949361PMC
March 2021

The Robson classification for caesarean section-A proposed method based on routinely collected health data.

PLoS One 2020 30;15(11):e0242736. Epub 2020 Nov 30.

Medical Directorate, Inselspital, University Hospital of Bern, Berne, Switzerland.

Background: With an increasing rate of caesarean sections as well as rising numbers of multiple pregnancies, valid classifications for benchmarking are needed. The Robson classification provides a method to group cases with caesarean section in order to assess differences in outcome across regions and sites. In this study we set up a novel method of classification by using routinely collected health data. We hypothesize i that routinely collected health data can be used to apply complex medical classifications and ii that the Robson classification is capable of classifying mothers and their corresponding newborn into meaningful groups with regard to outcome.

Methods And Findings: The study was conducted at the coding department and the department of obstetrics and gynecology Inselspital, University Hospital of Bern, Switzerland. The study population contained inpatient cases from 2014 until 2017. Administrative and health data were extracted from the Data Warehouse. Cases were classified by a Structured Query Language code according to the Robson criteria using data from the administrative system, the electronic health record and from the laboratory system. An automated query to classify the cases according to Robson could be implemented and successfully validated. A linkage of the mother's class to the corresponding newborn could be established. The distribution of clinical indicators was described. It could be shown that the Robson classes are associated to outcome parameters and case related costs.

Conclusions: With this study it could be demonstrated, that a complex query on routinely collected health data would serve for medical classification and monitoring of quality and outcome. Risk-stratification might be conducted using this data set and should be the next step in order to evaluate the Robson criteria and outcome. This study will enhance the discussion to adopt an automated classification on routinely collected health data for quality assurance purposes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242736PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703923PMC
January 2021

EULAR recommendations for a core data set for pregnancy registries in rheumatology.

Ann Rheum Dis 2021 01 14;80(1):49-56. Epub 2020 Oct 14.

Epidemiology and Health Care Research, German Rheumatism Research Center Berlin, Berlin, Germany.

Background And Objective: There is an urgent need for robust data on the trajectories and outcomes of pregnancies in women with inflammatory rheumatic diseases (IRD). In particular when rare outcomes or rare diseases are to be investigated, collaborative approaches are required. However, joint data analyses are often limited by the heterogeneity of the different data sources.To facilitate future research collaboration, a European League Against Rheumatism (EULAR) Task Force defined a core data set with a minimum of items to be collected by pregnancy registries in rheumatology covering the period of pregnancy and the 28-day neonatal phase in women with any underlying IRD.

Methods: A stepwise process included a two-round Delphi survey and a face-to-face meeting to achieve consensus about relevant items.

Results: A total of 64 multidisciplinary stakeholders from 14 different countries participated in the two rounds of the Delphi process. During the following face-to-face meeting of the EULAR Task Force, consensus was reached on 51 main items covering 'maternal information', 'pregnancy' and 'treatment'. Generic instruments for assessment are recommended for every item. Furthermore, for the five most frequent IRDs rheumatoid arthritis, spondyloarthritis, juvenile idiopathic arthritis, systemic lupus erythematosus and other connective tissue diseases, disease-specific laboratory markers and disease activity measurements are proposed.

Conclusion: This is the first consensus-based core data set for prospective pregnancy registries in rheumatology. Its purpose is to stimulate and facilitate multinational collaborations that aim to increase the knowledge about pregnancy course and safety of treatment in women with IRDs during pregnancy.
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http://dx.doi.org/10.1136/annrheumdis-2020-218356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788063PMC
January 2021

Effects of early aspirin therapy on utero-placental hemodynamics in patients at risk of preeclampsia.

J Matern Fetal Neonatal Med 2020 Jul 30:1-7. Epub 2020 Jul 30.

Department of Obstetrics and Gynecology, Inselspital, University of Bern, Bern, Switzerland.

Objectives: To evaluate the effects of early aspirin therapy on the mean pulsatility index of both uterine arteries (utA PI) at 1st and 2nd trimester in women at risk of preeclampsia (PE).

Methods: Uterine artery (utA) blood flow characteristics were obtained in 315 women, 73 women at risk for PE and early aspirin treatment (group 1), 124 without specific risk factors and no aspirin treatment (group 2) and 118 women with manifest PE (group 3). Mean utA PI of group 1 and group 2 were compared within and between the groups at the 1st and 2nd trimester time points. Furthermore, values at 2nd trimester were compared with those of group 3. Observed to expected mean utA PI ratio (O/E ratio) were calculated for comparison between the groups.

Results: Mean utA PI of group 1 was significantly higher in the 1st trimester compared to group 2 (1.74 vs. 1.47,  = .0117). In the 2nd trimester mean PI decreased significantly in both groups from 1.74 to 1.16 in group 1 and from 1.47 to 0.90 in group 2 ( < .0001). Nevertheless, the difference between the groups was significantly higher in the 2nd trimester than in the 1st trimester (0.29 vs. 0.27,  < .001). Correction for gestational age by analyzing mean utA O/E ratios showed a comparable pattern with a significantly decrease in both groups (1.40 to 1.10 in group 1 and 1.18 to 0.78 in group 2,  < .0001), but a significant higher decrease in the 2nd trimester in group 2 (0.31 vs.0.22,  < 0001). The prevalence of PE was 15.1% (11/73) in group 1 (4 early/7 late onset PE) and 4.7% (6/124) in group 2 (1 early/5 late onset). Mean utA PI and O/E ratio obtained in the 2nd trimester were higher in all PE cases with no significant difference between early and late onset PE (1.49/1.57 and 1.25/1.36 in group 1 and 0.80/0.97 and 0.77/0.99 in group 2). However, mean utA PI and O/E ratio decreased in all cases without PE in both groups, whereas mean utA PI was 1,37 and O/E-ratio was 1,29 in patients with manifest PE at admission, with significantly higher values in early onset than in late onset PE (1.45/1.31 vs. 1.07/1.02,  < .0001).

Conclusions: Our results show that early aspirin treatment leads to a decrease of elevated mean utA PI between 1st and 2nd trimester in patients at elevated risk for PE which is inferior to the decrease observed in women at standard risk for PE. While aspirin improves trophoblast invasion during early second trimester, vascular resistance remains well above average levels. Limited vascular remodeling capacity in the utero-placental perfusion area seems to be the explanation why aspirin does not abrogate PE in all women and has little effect on birth weight. Another explanation might be that a dose of 100 mg aspirin was used as compared to the 150 mg which is recommended today. Our findings underscore the need to study the effects of intervention already during the early stages of trophoblast invasion in the first trimester.
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http://dx.doi.org/10.1080/14767058.2020.1786048DOI Listing
July 2020

The Influence of Various Cerebral and Extracerebral Pathologies on Apparent Diffusion Coefficient Values in the Fetal Brain.

J Neuroimaging 2020 07 17;30(4):477-485. Epub 2020 Jun 17.

Institute of Diagnostic and Interventional Neuroradiology, Bern University Hospital, Bern, Switzerland.

Background And Purpose: The changing MRI signal accompanying brain maturation in fetal brains can be quantified on apparent diffusion coefficient (ADC) maps. Deviations from the natural course of ADC values may reflect structural pathology. The purpose of this study was to determine the influence of fetal pathologies on the ADC values in different regions of the fetal brain and their evolution with increasing gestational age.

Methods: This was a retrospective study of 291 fetuses evaluated between the 14th and the 40th week of gestation using diffusion-weighted imaging (DWI). Fetuses with normal MRI findings but sonographically suspected pathology or fetuses with abnormalities not affecting the brain were analyzed in the control group and compared to fetuses suffering from different pathologies like hydrocephalus/ventriculomegaly, brain malformations, infections, ischemia/hemorrhage, diaphragmatic hernias, and congenital heart disease. Pairwise ADC measurements in each side of the white matter (WM) of the frontal, parietal, and occipital lobes, in the basal ganglia and the cerebellum, as well as a single measurement in the pons were performed and were plotted against gestational age.

Results: In the control group, brain maturation followed a defined gradient, resulting in lower ADC values in the most mature regions. Each disorder group experienced abnormal patterns of evolution of the ADC values over time deviating from the expected course.

Conclusions: The ADC values in different regions of the fetal brain and their evolution with increasing gestational age are influenced by pathologies compromising the cerebral maturation.
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http://dx.doi.org/10.1111/jon.12727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383773PMC
July 2020

High prevalence of severe vitamin D deficiency during the first trimester in pregnant women in Switzerland and its potential contributions to adverse outcomes in the pregnancy.

Swiss Med Wkly 2020 May 28;150:w20238. Epub 2020 May 28.

Department of Obstetrics and Gynaecology, University Hospital Bern, Inselspital, University of Bern, Switzerland.

Purpose: Vitamin D is primarily known for its role in bone health. However, it has a much more diverse role in the human metabolism. Specifically, deficiency of vitamin D has recently been studied for its possible role in adverse pregnancy outcomes such as preeclampsia, gestational diabetes and preterm birth. Vitamin D levels largely depend on exposure to the sun and are influenced by nutritional habits at only a minimal level. In Switzerland, it is estimated that 40–50% of the population is vitamin D deficient. No specific data on pregnant women is available. The recommendations of the Swiss Federal Commission for Nutrition include a supplement of 600 IU of vitamin D to all pregnant women, despite the lack of data for this population in Switzerland. The primary aim of this study was to determine the prevalence of vitamin D deficiency among the population of pregnant women receiving prenatal care and giving birth at our clinic. We assumed that the prevalence of vitamin D deficiency in pregnant women in Switzerland is significantly higher than what has been estimated. Therefore, the current recommendations for vitamin D supplementation in pregnant women may be insufficient to achieve appropriate vitamin D levels. Furthermore, we aimed to address the issue of the potential influence of vitamin D deficiency on adverse pregnancy outcomes.

Methods: We performed a retrospective, observational cross-sectional study of 1382 pregnant women attending prenatal care at our department between 2012 and 2015. Serum 25-dihydroxycholecalciferol (25(OH)D) levels were determined in the first trimester, and the patient’s characteristics, the course of the pregnancy, any complications, the delivery and the neonatal outcome were analysed. The risk factors for vitamin D deficiency and its correlation with adverse pregnancy outcomes were assessed using a multivariate analysis.

Results: The clear majority (73.23%) of the population studied were found to be vitamin D deficient, with serum levels of 25(OH)D <50 nmol/l. More importantly, severe vitamin D deficiency (25(OH)D levels below 25 nmol/l) was present in one third (34.2%) of all pregnant women. The mean 25(OH)D level was 36.72 ± 19.63 nmol/l. In the multivariate analysis, those with a high BMI and who belonged to ethnicities comprising people who are generally dark-skinned were found to be associated with lower 25(OH)D serum levels (p <0.0001). We detected a seasonal influence: the mean 25(OH)D level was significantly higher during the summer season (April–September) compared to the winter season (October–March) (p <0.0001). We found an association between low 25(OH)D serum level and gestational diabetes (p = 0.0116). Surprisingly, a low 25(OH)D level was also associated with decreased incidence of postpartum hemorrhage and placental retention (p = 0.02). We found no association between the 25(OH)D serum level and preeclampsia, preterm birth, postdate pregnancy, miscarriage, intrauterine growth restriction, bacterial vaginosis, mode of delivery, or neonatal birth weight and length.

Conclusion: We performed a retrospective analysis of serum 25(OH)D concentrations in pregnant Swiss women and found a mean serum 25(OH)D level of about 37 nmol/l and that one third of the overall study population had a serum 25(OH)D level below 25 nmol/l, and were thus seriously vitamin D deficient. Furthermore, the data demonstrate that vitamin D deficiency is associated with gestational diabetes. The current recommendations of vitamin D supplementation of 600 IU in pregnant women are therefore insufficient, and novel strategies, such as general screening for vitamin D deficiency, pre-conceptional timing of the supplementation and individually tailored dosing of vitamin D supplementation seem mandatory, potentially leading to improved maternal health and benefits to children’s long-term health in Switzerland and worldwide. (trial registration ClinicalTrial.gov. Identifier: NCT02904720).
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http://dx.doi.org/10.4414/smw.2020.20238DOI Listing
May 2020

First assessed cervical dilatation: is it associated with oxytocin augmentation during labour? A retrospective cohort study in a university hospital in Switzerland.

Midwifery 2020 Jun 26;85:102683. Epub 2020 Feb 26.

Midwifery Research and Education Unit, Hannover Medical School, Germany. Electronic address:

Objectives: The primary objective of this study was to examine the association between the first assessed cervical dilatation in a labourward and the use of oxytocin augmentation during labour. Further analysis was performed by examining the actual stage of labour at the point oxytocin was first administered to those women.

Design: Retrospective cohort study with the data collected from the medical records of the hospital.

Setting: University Hospital Bern, Switzerland PARTICIPANTS: 1933 term nulliparous and multiparous women with a singleton pregnancy giving birth during the period June 2013 and May 2017, representing Robson groups 1 and 3.

Measurements And Findings: Descriptive statistics and multivariable logistic regression models were performed. It was found that for the entire process of labour, nulliparous and multiparous women (n = 1933) with a first cervical dilatation of 5 or more cm were less likely to be augmented with oxytocin (OR 0.64, 95% CI 0.46; 0.88 and OR 0.56, 95% CI 0.38; 0.82, respectively) compared to women with a first cervical dilatation of less than 5 cm. Out of these augmented women (n = 746) having a first cervical dilatation of 5 or more cm, they had a lower likelihood of being augmented during the first stage of labour compared to women with a first cervical dilatation of less than 5 cm (OR 0.45, 95% CI 0.29; 0.7 for nulliparae and OR 0.32, 95% CI 0.16; 0.6 for multiparae). Additionally, it was observed that other factors contributed to the application of oxytocin. One such example was that epidural analgesia was associated with a high risk of oxytocin augmentation in nulliparae (OR 13.88, 95% CI 9.29; 20.74) and multiparae (OR 15.52, 95% CI 9.94; 24.22). The application of oxytocin was also found to affect the caesarean section rate in nulliparous and multiparous women as it was 20% and 13% respectively for those with oxytocin versus 13% and 4% respectively for those without oxytocin.

Key Conclusions: Early admission to the labourward is associated with an increased use of oxytocin to augment labour, particularly, during the first stage of labour. Epidural analgesia is a main predictor for oxytocin augmentation in nulliparous and multiparous women.

Implications For Practice: Pregnant women warrant more appropriate support during early labour, avoiding early maternal exhaustion and excessive obstetrical interventions.
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http://dx.doi.org/10.1016/j.midw.2020.102683DOI Listing
June 2020

Is computerized cardiotocography useful in monochorionic twins with selective intrauterine growth restriction?

J Matern Fetal Neonatal Med 2020 Jan 12:1-6. Epub 2020 Jan 12.

Department of Obstetrics and Gynaecology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

To assess the value of using computerized cardiotocography (cCTG) short-term variation (STV) for intrapartum monitoring in monochorionic twins (MC) complicated by selective intrauterine growth restriction (sIUGR). All available cCTGs retrieved from computerized medical records of MC with sIUGR were retrospectively studied regarding the behavior of the STV. sIUGR was defined as intertwin estimated fetal weight (EFW) discordance of ≥20% with the abdominal circumference (AC) below the fifth percentile and/or the EFW of the smaller twin below the 10th percentile. The sIUGR classification system proposed by Gratacos et al. was used using types I-III on the basis of umbilical artery Doppler characteristics of the IUGR twin. The admission (entry) STV and final pre-delivery (last) STV values were analyzed. Cases with intrauterine demise, with structural or chromosomal abnormalities, with twin anemia polycythemia sequence (TAPS) and/or twin-to-twin transfusion syndrome (TTTS) were excluded. During the study period, 64 consecutive cases were managed within our department. Thirty-two cases fulfilled the inclusion criteria for analysis. Mean gestational age at assessment and at delivery was 28.4 ± 2.7 and 31.5 ± 2.2 weeks, respectively. The entry STV and last STV before delivery were not statistically different (mean IUGR STV entry: 9.3 ± 3.4 ms versus last 8 ± 2.2 ms;  = .051; mean co-twin STV entry: 9.1 ± 2.8 ms versus last 9.2 ± 3 ms;  = .87). Neither was the sIUGR-type adjusted STV. In MC pregnancies complicated by sIUGR, the cCTG STV does not distinguish between fetuses, nor does it show differences in cases of fetal deterioration monitored by conventional CTG.
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http://dx.doi.org/10.1080/14767058.2020.1712708DOI Listing
January 2020

Changepoint analysis of gestational age and birth weight: proposing a refinement of Diagnosis Related Groups.

Pediatr Res 2020 04 12;87(5):910-916. Epub 2019 Nov 12.

Department of Obstetrics & Gynecology, University Hospital of Bern, Berne, Switzerland.

Background: Although the complexity and length of treatment is connected to the newborn's maturity and birth weight, most case-mix grouping schemes classify newborns by birth weight alone. The objective of this study was to determine whether the definition of thresholds based on a changepoint analysis of variability of birth weight and gestational age contributes to a more homogenous classification.

Methods: This retrospective observational study was conducted at a Tertiary Care Center with Level III Neonatal Intensive Care and included neonate cases from 2016 through 2018. The institutional database of routinely collected health data was used. The design of this cohort study was explorative. The cases were categorized according to WHO gestational age classes and SwissDRG birth weight classes. A changepoint analysis was conducted. Cut-off values were determined.

Results: When grouping the cases according to the calculated changepoints, the variability within the groups with regard to case related costs could be reduced. A refined grouping was achieved especially with cases of >2500 g birth weight. An adjusted Grouping Grid for practical purposes was developed.

Conclusions: A novel method of classification of newborn cases by changepoint analysis was developed, providing the possibility to assign costs or outcome indicators to grouping mechanisms by gestational age and birth weight combined.
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http://dx.doi.org/10.1038/s41390-019-0669-0DOI Listing
April 2020

Angiogenic profiling in HELLP syndrome cases with or without hypertension and proteinuria.

Eur J Obstet Gynecol Reprod Biol 2019 Dec 22;243:93-96. Epub 2019 Oct 22.

Department of Obstetrics and Gynecology, Inselspital, Bern University Hospital, University of Bern, Switzerland. Electronic address:

Objectives: Angiogenic profiling with the use of sFlt-1/PlGF ratio (soluble fms-like tyrosine kinase-1/placental growth factor) can be helpful to characterize women with signs of impending preeclampsia (PE). However, little is known about the angiogenic profile of pregnancies complicated by HELLP syndrome. The aim of this study was to examine the relationship of angiogenic profiles in cases of HELLP syndrome with and without classical signs of preeclampsia.

Study Design: The angiogenic profile of pregnant women with singleton gestation and isolated PE (group 1), PE associated with HELLP syndrome (group 2), and isolated HELLP syndrome (group 3) from 01/2011 to 03/2018, were compared. To overcome gestational age dependent angiogenic behavior, cases (group 3) were matched 1:2 with cases from group 1 and 2. Matching criteria was gestational age (±1 week). PE and HELLP syndrome were defined according to the international Society for the Study of Hypertension in Pregnancy (ISSHP) statement 2014.

Results: During the observational period, 244 women could be included in the study. Of those, 237 (97.1%) were diagnosed with PE. In 42 cases (17.2%) PE was associated with HELLP syndrome while 7 (2.9%) patients were diagnosed with isolated HELLP syndrome. Angiogenic profiles in terms of sFlt-1/PlGF ratios differed significantly between the three groups, showing highest levels in group 2 (PE/HELLP) while cases with isolated HELLP demonstrated the lowest ratios and sFlt-1 values (p = 0.01).

Conclusion: We conclude that isolated HELLP syndrome is rare and seems to be a particular entity expressing a different angiogenic behaviour compared to classical PE or PE associated with HELLP syndrome.
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http://dx.doi.org/10.1016/j.ejogrb.2019.10.021DOI Listing
December 2019

FIRST TRIMESTER SCREENING FOR PREECLAMPSIA - A SYSTEMATIC REVIEW.

Hypertens Pregnancy 2020 Feb 31;39(1):1-11. Epub 2019 Oct 31.

Department of Obstetrics and Gynecology, University Hospital, University of Bern, Bern, Switzerland.

To increase the detection rate of preterm preeclampsia (PE) first trimester combined screening tests are being developed. The aim of this review is to create an overview of the currently investigated screening markers, algorithms and their validations. Comprehensive review of the literature concerning first trimester screening for PE Studies investigating a total of 160 biochemical, 6 biophysical and 14 ultrasound markers could be identified. Of the 21 algorithms published, mainly the algorithm published by the Fetal Medicine Foundation London has been validated. This algorithm performes significantly better than screening by anamnestic risk factors only.
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http://dx.doi.org/10.1080/10641955.2019.1682009DOI Listing
February 2020

Cervico-vaginal placental α-macroglobulin-1 combined with cervical length for the prediction of preterm birth in women with threatened preterm labor.

Acta Obstet Gynecol Scand 2020 03 28;99(3):357-363. Epub 2019 Oct 28.

Department of Obstetrics and Gynecology, University Hospital Bern and University of Bern, Bern, Switzerland.

Introduction: Preterm birth is a major cause of neonatal morbidity and mortality. There is an urgent need to accurately predict imminent delivery to enable necessary interventions such as tocolytic, glucocorticoid, and magnesium sulfate administration. We aimed to evaluate placental α-macroglobulin-1 as a new diagnostic marker in the prediction of preterm birth.

Material And Methods: We performed a prospective observational trial in women with intact membranes between 24 and 36 weeks of gestation. We included both women with and without threatened preterm labor symptoms. We evaluated the test performance of placental α-macroglobulin-1 measurements in cervicovaginal fluid regarding three different presentation-to-delivery intervals: ≤2, ≤7, ≤14 days. In addition, we calculated placental α-macroglobulin-1 performance in combination with other prognostic factors such as ultrasonographic cervical length measurements.

Results: We included 126 women in the study. We detected high specificity (97%-98%) and negative predictive value (89%-97%) for placental α-macroglobulin-1 at all time intervals. We assessed placental α-macroglobulin-1 in combination with cervical length measurements (≤15 mm) in the sub-group of women presenting with threatened preterm labor symptoms (n = 63) and detected high positive predictive values (100%) for 7- and 14-day presentation-to-delivery intervals.

Conclusions: Our study provides evidence that placental α-macroglobulin-1 testing in cervicovaginal fluid, in combination with cervical length measurements, accurately predicts preterm birth in women with preterm labor symptoms. This novel test combination may be used clinically to triage women presenting with threatened preterm labor, avoiding overtreatment and unnecessary hospitalizations.
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http://dx.doi.org/10.1111/aogs.13744DOI Listing
March 2020

Systolic Hypertension, Preeclampsia-Related Mortality, and Stroke In California.

Obstet Gynecol 2019 10;134(4):880

University of Bern Medical School, Bern, Switzerland.

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http://dx.doi.org/10.1097/AOG.0000000000003493DOI Listing
October 2019

Adverse perinatal outcomes for obese women are influenced by the presence of comorbid diabetes and hypertensive disorders.

Sci Rep 2019 07 5;9(1):9793. Epub 2019 Jul 5.

Health Department, Bern University of Applied Sciences, Murtenstrasse 10, 3008, Bern, Switzerland.

Maternal obesity often occurs together with comorbid diabetes and hypertensive disorders. All three conditions are independently associated with negative perinatal outcomes. Our objective was to determine the risk and burden of adverse perinatal outcome that could be attributed to maternal obesity in combination with a comorbid status. We analyzed data from 324'664 singleton deliveries in Switzerland between 2005 and 2016. For the association of maternal obesity in the presence or absence of comorbidities with various perinatal outcomes, we estimated adjusted relative risk (RR) using multivariable regression modeling and determined the multivariable-adjusted attributable fraction of the population (AFp). Obesity was a main predictor for macrosomia, fracture of the clavicle, failure to progress in labor and prolonged labor. By stratifying women based on comorbidities, we identified significantly increased risk for preterm birth and early neonatal death only for women diagnosed with a comorbidity. However, various other outcomes were independently associated with either obesity or comorbidities. The AFp showed greatest reduction in comorbidities (15.4/15.0/13.2%), in macrosomia (6.3%) and in shoulder dystocia (4.8%) if all women were to become non-obese. We suggest that comorbidities such as diabetes and hypertensive disorders should be considered when relating maternal obesity to adverse perinatal outcomes.
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http://dx.doi.org/10.1038/s41598-019-46179-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611811PMC
July 2019

EULAR recommendations for the management of antiphospholipid syndrome in adults.

Ann Rheum Dis 2019 10 15;78(10):1296-1304. Epub 2019 May 15.

Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.

The objective was to develop evidence-based recommendations for the management of antiphospholipid syndrome (APS) in adults. Based on evidence from a systematic literature review and expert opinion, overarching principles and recommendations were formulated and voted. High-risk antiphospholipid antibody (aPL) profile is associated with greater risk for thrombotic and obstetric APS. Risk modification includes screening for and management of cardiovascular and venous thrombosis risk factors, patient education about treatment adherence, and lifestyle counselling. Low-dose aspirin (LDA) is recommended for asymptomatic aPL carriers, patients with systemic lupus erythematosus without prior thrombotic or obstetric APS, and non-pregnant women with a history of obstetric APS only, all with high-risk aPL profiles. Patients with APS and first unprovoked venous thrombosis should receive long-term treatment with vitamin K antagonists (VKA) with a target international normalised ratio (INR) of 2-3. In patients with APS with first arterial thrombosis, treatment with VKA with INR 2-3 or INR 3-4 is recommended, considering the individual's bleeding/thrombosis risk. Rivaroxaban should not be used in patients with APS with triple aPL positivity. For patients with recurrent arterial or venous thrombosis despite adequate treatment, addition of LDA, increase of INR target to 3-4 or switch to low molecular weight heparin may be considered. In women with prior obstetric APS, combination treatment with LDA and prophylactic dosage heparin during pregnancy is recommended. In patients with recurrent pregnancy complications, increase of heparin to therapeutic dose, addition of hydroxychloroquine or addition of low-dose prednisolone in the first trimester may be considered. These recommendations aim to guide treatment in adults with APS. High-quality evidence is limited, indicating a need for more research.
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http://dx.doi.org/10.1136/annrheumdis-2019-215213DOI Listing
October 2019

Ultra-high sensitive C-reactive protein during normal pregnancy and in preeclampsia: a pilot study.

J Hypertens 2019 05;37(5):1012-1017

Department of Obstetrics and Gynaecology.

Introduction: Angiogenic and inflammatory factors have been shown to play an important role in the pathogenesis of preeclampsia. However, there is little information on their interaction. The aims of this study were to investigate the longitudinal pattern of inflammatory markers, such as interleukin-6 (IL-6) and C-reactive protein (CRP) using a novel ultra-high sensitive assay method (uhsCRP), and to explore their relationship with angiogenic factors such as placental growth factor (PLGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and vascular endothelial growth factor (VEGF) in normal pregnancies and pregnancies complicated by preeclampsia.

Materials And Methods: Serum levels of uhsCRP, IL-6, PLGF, VEGF and s-Flt-1 were longitudinally determined in 16 women with normal, singleton healthy pregnancies at 7-13, 17-22, 27-31 and 37-41 weeks of gestation by ELISA. uhsCRP was measured using a ultra-high sensitivity ELISA test. Serum of women with preeclampsia (n = 15) was available only once, usually in the third trimester of pregnancy. Women with premature rupture of membranes (PROM) or infection such as chorioamnionitis were excluded. Spearman rank correlation, logistic regression, ROC analysis, ANOVA and Mann-Whitney U-test were used for statistical purposes.

Results: In normal pregnancies, serum uhsCRP showed a gestational age-dependent increase (r = 0.40; P < 0.001). In women suffering from preeclampsia, uhsCRP levels were higher than in gestational age-matched controls (18010 ± 4763 versus 3026 ± 587 ng/ml; P < 0.001). Similarly, serum IL-6 levels increased throughout pregnancy and correlated with uhsCRP in normal pregnancies and in preeclampsia (n = 64, r = 0.37; P < 0.01 and n = 15, r = 1.00, P < 0.0001). uhsCRP levels were positively correlated with sFlt-1 levels (n = 64, r = 0.34; P < 0.01).

Conclusion: The increases in uhsCRP (and IL-6) serum levels with advancing gestation indicate a shift towards an inflammatory state during normal pregnancy. The excessive rise in uhsCRP and sFlt-1 in preeclampsia indicate that both may be involved in its pathogenesis. uhsCRP may be useful as an early marker for preeclampsia and studies defining the pattern of its rise throughout pregnancies at risk are urgently needed.
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http://dx.doi.org/10.1097/HJH.0000000000002003DOI Listing
May 2019

Shrunken pore syndrome, preeclampsia, and markers of NO metabolism in pregnant women during the first trimester.

Scand J Clin Lab Invest 2019 Feb - Apr;79(1-2):91-98. Epub 2019 Feb 20.

i Kantonsspital Graubünden , Zentrallabor , Chur , Switzerland.

Shrunken pore syndrome (SPS) is a condition that manifests itself as the decreased renal clearance of low-molecular-weight proteins but normal clearance of creatinine. Pregnant women with evidence of SPS during the first trimester have an increased risk of developing preeclampsia (PE). The nitric oxide (NO) metabolism markers arginine and ADMA, especially their ratio (Arg/ADMA), are recognized markers of endothelial dysfunction. The aim of this nested case-control study was to establish first-trimester reference intervals (RI) for markers of NO metabolism and to study these markers in women with evidence of SPS at the end of the first trimester. Seventy-four women were stratified in the first trimester according to evidence of SPS (SPS + or SPS-) and the occurrence of PE during subsequent pregnancy (PE + or PE-), as follows: SPS-/PE-, SPS+/PE-, SPS-/PE+, and SPS+/PE+. RIs were determined according to the CLSI EP28-A3c guidelines. Serum Arg and ADMA levels were analyzed. The Arg and ADMA concentrations did not differ among the four groups. However, women in the SPS+/PE + group had a significantly lower Arg/ADMA ratio than those in the other 3 groups (p = .02). In conclusion, we defined the first-trimester RI of Arg, ADMA and the Arg/ADMA ratio as markers of NO metabolism. Our results suggest that SPS in the first trimester predicts a pathophysiological hallmark of subsequent PE, i.e. lower NO production leading to increased vessel tone. Early identification of women at risk for later PE could lead to adaptive prophylactic interventions, such as supplementation with Arg or an NO-donor drug in order to mitigate the risk of developing PE.
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http://dx.doi.org/10.1080/00365513.2019.1568150DOI Listing
August 2019

Placental mesenchymal dysplasia: An underdiagnosed placental pathology with various clinical outcomes.

Eur J Obstet Gynecol Reprod Biol 2019 Mar 17;234:155-164. Epub 2019 Jan 17.

Materno-Fetal and Obstetrics Research Unit, Department of Obstetrics and Gynecology, University Hospital, Lausanne, Switzerland. Electronic address:

Background: Placental mesenchymal dysplasia (PMD) is a rare vascular and connective placental anomaly, which is often associated with severe fetal and/or maternal complications. The diversity of presentation of PMD challenges diagnosis and effective pregnancy management.

Objective: We aimed to review cases presenting at 7 tertiary centers worldwide over the last decade and to study the occurrence of obstetric and neonatal complications.

Study Design: Pathology databases from 7 tertiary hospitals were screened for cases of PMD (between 2007-2017). Pregnancy history, outcomes and ultrasound images were then reviewed for each case.

Results: Twenty-two cases of PMD were identified. Mean gestational age at diagnosis was 23 weeks (16-39 weeks). Prenatal biochemical screening was abnormal in 8 cases (36%). Of the 12 cases that underwent invasive genetic testing, 4 were abnormal. Six patients (27%) developed maternal complications (preeclampsia/gestational hypertension). Fetal growth restriction was identified in 11 cases (50%) and fetal death in 4 (18%). Four (18%) pregnancies were terminated, 9/14 (64%) delivered preterm and only three (14%) progressed normally. Fourteen babies were born alive; 5 (35%) died in the first sixty-one days after birth, 5 (35%) had transient thrombopenia and 1 (7%) had developmental delay at last follow-up. Our series identified four potential new associations with PMD: placental triploidy mosaicism, CHARGE syndrome, fetal pleuropulmonary blastoma and fetal skeletal dysplasia.

Conclusions: PMD was substantially under-diagnosed before delivery in this cohort. Sonographers, fetal medicine specialists, obstetricians and pathologists should all suspect PMD in cases of an enlarged placenta and should look for fetal abnormalities. Diagnostic genetic testing should be discussed to exclude partial molar pregnancy. Close pregnancy follow-up is indicated due to the high risk of associated fetal or maternal adverse outcomes.
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http://dx.doi.org/10.1016/j.ejogrb.2019.01.014DOI Listing
March 2019

The Vermian-Crest Angle: A New Method to Assess Fetal Vermis Position within the Posterior Fossa Using 3-Dimensional Multiplanar Sonography.

Fetal Diagn Ther 2019 5;46(4):223-230. Epub 2018 Dec 5.

Department of Obstetrics and Gynecology, University of Bern, Bern, Switzerland.

Background: Normal morphometry of the vermis and its relation to the posterior fossa (PF) rule out most major anomalies of the cerebellum. However, accurate categorization of the position and size of the fetal vermis remains a challenge.

Objective: Our aim was to test a new method to assess the position and size of fetal vermis on 3-dimensional ultrasound (3D-US).

Methods: We measured the vermian-crest angle (VCA) in normal fetuses using multiplanar 3D-US. We also assessed the diameters (superoinferior, anteroposterior, and horizontal) and volume of the vermis. The Spearman rank test and linear and polynomial regression analyses were used for statistical purposes.

Results: We included 126 fetuses. Mean ± SD gestational age (GA) was 26.3 ± 4.6 (range 17-35.5) weeks. Mean ± SD superoinferior, anteroposterior, and horizontal diameters were 16.2 ± 4.9, 11.2 ± 3.6, and 5.6 ± 1.6 mm, respectively. Median (range) vermian volume was 0.50 (0.05-2.9) cm3. The VCA was 64.49° ± 11.45. We found no correlation between GA and VCA (r = 0.15; p = 0.13), a linear correlation between GA and vermian diameters, and a quadratic correlation between GA and vermian volume.

Conclusions: We provide a new method to assess vermian position and size within the PF using 3D-US. The combined information may be of value for screening purposes, particularly to differentiate between the various pathological situations encountered within the PF.
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http://dx.doi.org/10.1159/000494721DOI Listing
March 2020

Nomograms of the Fetal Sylvian Fissure and Insular Lobe throughout Gestation: A Multicentric, Ultrasonographic Cross-Sectional Study.

Fetal Diagn Ther 2019 12;45(5):325-331. Epub 2018 Jul 12.

Department of Obstetrics and Gynecology, University of Bern, Bern, Switzerland.

Introduction: Anomalies in cortical development are often associated with an adverse outcome, but prenatal diagnosis is often impeded by the limited knowledge about normal sulci biometries throughout fetal brain development. Our aim was to provide two-dimensional ultrasonographical (2D US) nomograms of the depth of the Sylvian fissure (SF) and insular lobe (IL), as well as of the SF ratio throughout gestation in a large number of fetuses.

Materials And Methods: This was a prospective cross-sectional study of 329 normal singleton pregnancies. Measurements of the SF, IL, and SF ratio were obtained in a standard transthalamic plane of the fetal head. The SF ratio was defined as SF\SF + IL. All measurements were expressed by regression equations as a function of gestational age (GA) according to the method described by Royston and Wright. The first 38 measurements were repeated twice by 2 examiners to assess the reproducibility through the intraclass correlation coefficient (ICC).

Results: A significant correlation was found between GA and SF (r = 0.79; p < 0.0001) as well as IL (r = 0.77; p < 0.0001). Similarly, the SF ratio also showed a significant correlation with GA (r = 0.39; p < 0.0001). When interobserver variability was assessed, ICC was 0.97.

Conclusions: Prenatal 2D US measurements of SF and IL as well as the SF ratio may be feasible and reproducible using a standard view of the fetal head. Our nomograms may be used as a reference for assessing cortical development throughout pregnancy.
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http://dx.doi.org/10.1159/000490242DOI Listing
December 2019

Misoprostol vaginal insert versus misoprostol vaginal tablets for the induction of labour: a cohort study.

BMC Pregnancy Childbirth 2018 May 10;18(1):149. Epub 2018 May 10.

Department of Obstetrics and Gynaecology, Inselspital, Bern University Hospital, University of Bern, Effingerstrasse 102, CH-3010, Bern, Switzerland.

Background: Misoprostol vaginal insert for induction of labor has been recently reported to be superior to dinoprostone vaginal insert in a phase III trial, but has never been compared to vaginal misoprostol in another galenic form. The aim of this study was to compare misoprostol vaginal insert (MVI) with misoprostol vaginal tablets (MVT) for induction of labor in term pregnancies.

Methods: In this retrospective cohort study we compared 200 consecutive women induced with 200-μg misoprostol 24-h vaginal insert (Misodel®) with a historical control of 200 women induced with Misoprostol 25-μg vaginal tablets (Cytotec®) every 4-6 h. Main outcomes variables included induction-to-delivery interval, vaginal delivery within 24-h, incidence of tachysystole, mode of delivery, and neonatal outcome. A subanalysis in the MVI group was performed in order to identify predictive factors for tachysistole and vaginal delivery within 24 h.

Results: The time from induction to vaginal delivery was 1048 ± 814 min in the MVI group and 1510 ± 1043 min in the MVT group (p < 0.001). Vaginal delivery within 24-h occurred in 127 (63.5%) patients of the MVI group and in 110 (55%) patients of the MVT group (p < 0.001). Tachysystole was more common in the MVI group (36% vs. 18%; p < 0.001). However, no significant predictors of uterine tachysystole in MVI group have been identified in crude and fully adjusted logistic regression models. Bishop score was the only predictor for vaginal delivery within 24 h (p < 0.001) in MVI group. Caesarean delivery rate (27% vs. 20%) and vaginal-operative deliveries (15.5% vs. 15.5%) did not differ significantly between the two groups. Neonatal outcomes were similar in both groups.

Conclusions: MVI achieves a more vaginal delivery rate within 24 h and Tachysystole events compared to MVT. However, no differences in caesarean section, operative vaginal delivery, and neonatal outcomes are reported. No predictors of tachysistole after MVI administration have been identified. Bishop score and parity are the only predictors of vaginal delivery within 24 h after MVI administration.
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http://dx.doi.org/10.1186/s12884-018-1788-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946434PMC
May 2018

Standardized Management Protocol in Severe Postpartum Hemorrhage: A Single-Center Study.

Clin Appl Thromb Hemost 2018 Sep 18;24(6):884-893. Epub 2018 Apr 18.

1 Department of Hematology and Central Hematology Laboratory, University Hospital and University of Bern, Bern, Switzerland.

Severe postpartum hemorrhage (sPPH) is an obstetric emergency that needs prompt and effective therapy to reduce the risk of complications. In this study, women who developed sPPH (study cohort, n = 27) were treated according to a standardized management protocol prescribing sequential administration of uterotonic drugs, crystalloids, tranexamic acid, labile blood products, low-dose fibrinogen, and recombinant activated factor VII (rFVIIa). This group was compared to patients treated with different strategies during 2 preceding periods: an in-house guideline regulating the administration of rFVIIa (historical cohort 1, n = 20) and no specific guideline (historical cohort 2, n = 27). The management protocol was used over 33 months. The study cohort had a lower estimated blood loss ( P = .004) and required less red blood cell concentrates ( P = .007), fresh frozen plasma units ( P = .004), and platelet concentrates ( P = .020) compared to historical cohort 1 and historical cohort 2, respectively. The necessity of emergency postpartum hysterectomy was lower in the study group ( P = .012). In conclusion, in patients with sPPH treated with this standardized management protocol, we observed a decreased requirement of labile blood products and lower need to proceed to emergency postpartum hysterectomy.
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http://dx.doi.org/10.1177/1076029618758956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714733PMC
September 2018

Prenatal diagnosis of diaphanospondylodysostosis (DSD): a case report.

Clin Case Rep 2018 02 17;6(2):420-425. Epub 2018 Jan 17.

Department of Obstetrics & Gynecology Inselspital University of Bern Switzerland.

We present a case of diaphanospondylodysostosis (DSD) which showed increased nuchal translucency at 1st trimester and missing ossification of the lower spine, short ribs with posterior gaps, and absent nasal bone in midtrimester. Autopsy revealed additionally bilateral nephroblastomatosis. Molecular genetic analysis showed a new mutation in the BMPER gene.
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http://dx.doi.org/10.1002/ccr3.1368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5799658PMC
February 2018

Do late preterm twins face an increased neonatal morbidity compared with singletons?

Swiss Med Wkly 2018 4;148:w14581. Epub 2018 Jan 4.

Department of Paediatrics, Division of Neonatology, Bern University Hospital, University of Bern, Switzerland / University of Basel Children's Hospital (UKBB), Neonatology, Basel, Switzerland.

Objective: Late preterm infants (born between 34 0/7 and 36 6/7 weeks of gestation) have been shown to have a higher morbidity and mortality than term infants. Furthermore, twins, both term and preterm, have a higher neonatal morbidity than singletons. The aim of our study was to examine if late preterm twins consequently have twice the neonatal morbidity when both risk factors prematurity and multiple pregnancy are present.

Study Design: A retrospective single-centre study was conducted to compare neonatal outcome of late preterm singletons and late preterm twins born between 34 0/7 and 36 6/7 weeks of gestation as well as term twins with a gestational age from 37 0/7 to 41 6/7 weeks. Primary outcome was length of hospitalisation. Secondary outcome was neonatal morbidity.

Results: A total of 845 infants were included. Late preterm twins (n = 243) were hospitalised significantly longer than term twins (n = 107) (13.5 ± 8.0 vs 6.29 ± 2.0 days, p <0.001) and late preterm singletons (n = 495) (13.5 ± 8.0 vs 12.6 ± 8.6 days, p = 0.011). Hyperbilirubinaemia occurred significantly more often in late preterm singletons than in late preterm twins (49.7 vs 29.2%; p<0.001). Otherwise, no significant differences were detected regarding neonatal morbidities or mortality of late preterm singletons and late preterm twins. Late preterm twins had a significantly higher incidence of most morbidities than term twins.

Conclusion: Late preterm twins are hospitalised significantly longer than similar-aged singletons, but have otherwise similar neonatal morbidities. Hyperbilirubinaemia is less frequent in late preterm twins than late preterm singletons.
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http://dx.doi.org/10.4414/smw.2018.14581DOI Listing
September 2018

Safety and effectiveness of labour induction after caesarean section using balloon catheter or oxytocin.

Swiss Med Wkly 2017 8;147:w14532. Epub 2017 Nov 8.

Department of Obstetrics and Gynaecology, University Hospital and University of Bern, Switzerland; Department of Biomedical Research, University of Bern, Switzerland.

Aims Of The Study: Induction of labour after previous caesarean section (CS) is a challenge for obstetricians due to the increased risk of uterine rupture. Common methods for labour induction are balloon catheters and oxytocin as they are considered safe. However, the effectiveness remains unclear as currently available data are limited. Therefore, we aimed to determine safety and effectiveness of balloon catheter or oxytocin for labour induction after CS.

Methods: We included 179 consecutive women with a previous CS and labour induction in this retrospective study. We performed labour induction using a balloon catheter in case of a Bishop score of <6 and intact membranes, or oxytocin in the case of a Bishop score of >6 and/or premature rupture of membranes. The primary outcome was the rate of successful vaginal deliveries. We adjusted for multiple factors that may have impacted on the rate of vaginal delivery as well. The secondary outcomes were the rate of maternal and neonatal morbidities.

Results: We detected a vaginal delivery success rate of 45.8% in the catheter and of 63.9% in the oxytocin group. We identified previous vaginal birth as an independent predictive factor for successful vaginal delivery in both groups. Induction using oxytocin was a negative predictive factor for neonatal admissions. Multivariate analysis showed that post-term pregnancy decreased the likelihood of vaginal delivery. We did not detect any factors predicting uterine rupture or uterine dehiscence, which occurred with similar frequency in both groups. Finally, the neonatal admission rate was less likely with higher gestational age and oxytocin as an induction method, whereas previous vaginal birth increased the risk.

Conclusions: Our study indicates that induction of labour with balloon catheter or oxytocin seems to be safe in women with previous CS. Labour induction using a balloon catheter in women with previous CS and unfavourable cervix has a disappointingly low success rate. We identified factors influencing vaginal delivery success rates. Women with previous CS and indications for labour induction should be informed about vaginal birth success rates and the alternative of elective repeat CS needs to be discussed.
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http://dx.doi.org/10.4414/smw.2017.14532DOI Listing
July 2018

High first-trimester maternal blood cystatin C levels despite normal serum creatinine predict pre-eclampsia in singleton pregnancies.

Scand J Clin Lab Invest 2017 Dec 25;77(8):634-643. Epub 2017 Oct 25.

b Labormedizinisches Zentrum Dr. Risch , Department of Clinical Chemistry , Vaduz , Liechtenstein.

Early biochemical identification of women at high risk for the development of pre-eclampsia (PE) is still unsatisfactory. Renal markers measured during the first trimester were analysed to predict later occurrence of PE. A nested case-control study was conducted within the prospective predictive markers for the diagnosis of preeclampsia study. Pregnant women were included at the end of the first trimester and followed up until birth. Controls were matched to PE cases. Renal markers [i.e. creatinine, cystatin C (CysC), β microglobulin (B2M), β-trace protein (BTP), glomerular filtration rate estimations (eGFR) of the aforementioned markers, uric acid (UA), urea, and serum uromodulin (sUMOD)] were compared to placental growth factor (PlGF), a marker known to predict PE later in pregnancy. Reference intervals were determined for the different markers. In the 183 women (PE, n = 39; controls, n = 144), CysC, the CysC/PlGF ratio (p < .01) and UA were higher, whereas the eGFR/eGFR ratio (a marker of glomerular endothelial integrity and shrunken pore syndrome) and PlGF were lower in women who developed PE (p < .05 for all). Compromised filtration of the larger molecule CysC together with a normal creatinine, in a subset of PE cases (15.3%) was a unique, strong and independent predictor of later PE if the baseline CysC concentration was >0.85 mg/l. In conclusion, CysC and its derivatives as well as UA, indicating volume expansion, measured at the end of the first trimester are predictive of PE. Thus, women can be easily identified and followed as an early reduction in glomerular filtration quality poses a high risk for a subsequent development of PE.
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http://dx.doi.org/10.1080/00365513.2017.1393692DOI Listing
December 2017

Reference Ranges for Fetal Atrioventricular and Ventriculoatrial Time Intervals and Their Ratios during Normal Pregnancy.

Fetal Diagn Ther 2018 19;44(3):228-235. Epub 2017 Oct 19.

Background: The diagnostic assessment of fetal arrhythmias relies on the measurements of atrioventricular (AV) and ventriculoatrial (VA) time intervals. Pulsed Doppler over in- and outflow of the left ventricle and tissue Doppler imaging are well-described methods, while Doppler measurements between the left brachiocephalic vein and the aortic arch are less investigated. The aim of this study was to compare these methods of measurement, to find influencing factors on AV and VA times and their ratio, and to create reference ranges.

Methods: Echocardiography was performed between 16 and 40 weeks of gestation in normal singleton pregnancies. Nomograms for the individual measurements were created using quantile regression with Matlab Data Analytics. Statistical analyses were performed with GraphPad version 5.0 for Windows.

Results: A total of 329 pregnant women were enrolled. A significant correlation exists between AV and VA times and gestational age (GA) (p = 0.0104 to <0.0001, σ = 0.1412 to 0.3632). No correlation was found between the AV:VA ratio and GA (p = 0.08 to 0.60). All measurements differed significantly amongst the studied methods (p < 0.0001).

Conclusions: AV and VA intervals increase proportionally with GA; no other independent influencing factors could be identified. As significant differences exist between the three methods of assessment, it is crucial to use appropriate reference ranges to diagnose pathologies.
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http://dx.doi.org/10.1159/000481349DOI Listing
January 2019

First trimester combined screening for preeclampsia and small for gestational age - a single centre experience and validation of the FMF screening algorithm.

Swiss Med Wkly 2017 25;147:w14498. Epub 2017 Aug 25.

Department of Obstetrics and Gynaecology, University Hospital, University of Bern, Switzerland.

Aim Of The Study: Preeclampsia (PE) is associated with severe maternal and fetal morbidity in the acute presentation and there is increasing evidence that it is also an important risk factor for cardiovascular disease later in life. Therefore, preventive strategies are of utmost importance. The Fetal Medicine Foundation (FMF) London recently developed a first trimester screening algorithm for placenta-related pregnancy complications, in particular early onset preeclampsia (eoPE) requiring delivery before 34 weeks, and preterm small for gestational age (pSGA), with a birth weight <5th percentile and delivery before 37 weeks of gestation, based on maternal history and characteristics, and biochemical and biophysical parameters. The aim of this study was to test the performance of this algorithm in our setting and to perform an external validation of the screening algorithm.

Material And Methods: Between September 2013 and April 2016, all consecutive women with singleton pregnancies who agreed to this screening were included in the study. The proposed cut-offs of ≥1:200 for eoPE, and ≥1:150 for pSGA were applied. Risk calculations were performed with Viewpoint® program (GE, Mountainview, CA, USA) and statistical analysis with GraphPad version 5.0 for Windows.

Results: 1372 women agreed to PE screening; the 1129 with complete data and a live birth were included in this study. Nineteen (1.68%) developed PE: 14 (1.24%) at term (tPE) and 5 (0.44%) preterm (pPE, <37 weeks), including 2 (0.18%) with eoPE. Overall, 97/1129 (8.6%) screened positive for eoPE, including both pregnancies that resulted in eoPE and 4/5 (80%) that resulted in pPE. Forty-nine of 1110 (4.41%) pregnancies without PE resulted in SGA, 3 (0.27%) of them in pSGA. A total of 210/1110 (18.9%) non-PE pregnancies screened positive for pSGA, including 2/3 (66.7%) of the pSGA deliveries and 18/46 (39.1%) of term SGA infants.

Conclusion: Our results show that first trimester PE screening in our population performs well and according to expectations, whereas screening for SGA is associated with a high false positive rate.
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http://dx.doi.org/10.4414/smw.2017.14498DOI Listing
June 2018