Beatrice Mosimann

Fetal Fraction in Maternal Plasma Cell-Free DNA at 11-13 Weeks' Gestation: Effect of Maternal and Fetal Factors

Objective: It was the aim of this study to examine the possible effects of maternal and fetal characteristics on the fetal fraction in maternal plasma cell-free DNA (cfDNA) at 11–13 weeks’ gestation. Methods: In a nested case-control study, cfDNA was extracted from maternal plasma obtained before chorionic villous sampling from 300 euploid, 50 trisomy 21 and 50 trisomy 18 pregnancies at 11–13 weeks’ gestation. Chromosome-selective sequencing of maternal cfDNA non-polymorphic and polymorphic loci, where fetal alleles differ from maternal alleles, was used to determine the proportion of DNA which is of fetal origin. Multivariate regression analysis was used to determine which of the factors amongst maternal weight, racial origin, smoking status, plasma storage time, serum pregnancy-associated plasma protein (PAPP)-A and free β-subunit of human chorionic gonadotropin (β-hCG), fetal crown-rump length, nuchal translucency thickness, gender and karyotype were significant predictors of the fetal fraction. Results: Significant independent prediction of fetal fraction was provided by maternal weight, serum PAPP-A and serum free β-hCG multiples of the median, but not by other maternal characteristics, fetal karyotype, crown-rump length or nuchal translucency thickness. Fetal fraction increased with serum metabolite levels and decreased with maternal weight. Conclusions: The fetal fraction in maternal plasma cfDNA increases with serum PAPP-A and free β-hCG and decreases with maternal weight.

Maternal serum cytokines at 30-33 weeks in the prediction of preeclampsia.

The aim of this case–control study at 30–33 weeks, a few days or weeks before the clinical onset of preeclampsia (PE), was to assess whether serum concentrations of cytokines differ between patients who are destined to develop PE and those with uncomplicated pregnancies.

First-trimester glycosylated hemoglobin in women at high risk for gestational diabetes.

Our aim was to investigate the prognostic value of first‐trimester glycosylated hemoglobin (HbA1c) in pregnant women with risk factors for developing gestational diabetes mellitus (GDM).

Maternal serum ferritin at 11- to 13-week gestation in spontaneous early preterm delivery

Objective: To examine the potential value of maternal serum level of ferritin in the first trimester of pregnancy in the prediction of spontaneous early preterm delivery. Methods: Maternal serum concentration of ferritin at 11–13-week gestation was measured in a case-control study of singleton pregnancies delivering phenotypically normal neonates, including 30 cases with spontaneous delivery before 34 weeks and 90 matched controls delivering after 37 weeks. The median multiple of the median (MoM) serum ferritin in the two outcome groups was compared. Results: The median serum ferritin MoM was not significantly different in the spontaneous early preterm delivery group compared with the term delivery group (1.143, interquartile range [IQR] 0.578–2.383 vs. 1.059, IQR 0.641–1.644, p = 0.725). Conclusions: Measurement of maternal serum ferritin at 11–13 weeks is unlikely to be useful in screening for spontaneous early preterm delivery.

Importance of Timing First-Trimester Placental Growth Factor and Use of Serial First-Trimester Placental Growth Factor Measurements in Screening for Preeclampsia

Objective: The aims of this study were to test whether the performance of first-trimester placental growth factor (PlGF) in screening for preterm preeclampsia (PE) is gestational age dependent and to assess the value of serial first-trimester PlGF measurements in discriminating women at risk for PE. Methods: PlGF was measured in women with singleton pregnancies at their first antenatal visit at 8+0 to 10+6 and additionally at 11+0 to 14+0 weeks of gestation. The difference in absolute values of serial PlGF measurements was expressed as Δ-PlGF. Values were compared between pregnancies with normal outcome and those complicated by PE. Results: A total of 814 pregnancies were included, 18 (2.19%) developed PE that required delivery before 37 weeks of gestation. PlGF increases significantly from 8 to 14 weeks of gestation (ρ = 0.63; p < 0.0001) in normal pregnancies, but not so in preterm PE (ρ = 0.034; p = 0.893). PlGF discriminates between PE and uneventful pregnancies only after 10 weeks of gestation. Δ-PlGF was significantly lower in PE 5.3 (-1.1 to 9.3) pg/mL compared to uneventful pregnancies 17.3 (9.8-26.0) pg/mL (p = 0.0011). Conclusion: The discriminatory accuracy of PlGF increases from 10 to 14 weeks of gestation, and serial PlGF measurements might be of particular interest in PE screening.

Maternal serum tumour necrosis factor receptor 1 (TNF-R1) at 30-33 weeks in the prediction of preeclampsia.

Abstract Objective: To investigate the potential value of maternal serum concentration of tumour necrosis factor receptor 1 (TNF-R1) at 30–33 weeks’ gestation in the prediction of preeclampsia (PE) developing at or after 34 weeks. Methods: Serum TNF-R1 was measured at 11–13 and at 30–33 weeks’ gestation in a case-control study of 50 cases that developed PE at or after 34 weeks and 250 unaffected controls. The measured values of TNF-R1 were converted into multiples of the normal median (MoM) and the MoM values in the PE and control groups were compared. Results: The median MoM TNF-R1 was significantly increased at both 11–13 weeks (1.094 MoM versus 1.003 MoM) and at 30–33 weeks (1.101 MoM versus 1.006 MoM). In screening for PE by a combination of maternal characteristics and serum TNF-R1 at 30–33 weeks, the estimated detection rates of PE at false positive rates of 5% and 10% were 32.0% and 40.0%, respectively. Conclusion: Screening by maternal characteristics and serum TNF-R1 at 30–33 weeks could be effective in identifying some of the cases that will subsequently develop PE.

First-Trimester Placental Growth Factor in Screening for Gestational Diabetes.

Objective: The aim of this study was first to assess whether first-trimester serum concentrations of placental growth factor (PlGF) differ between patients with and without gestational diabetes (GDM) and second to test whether there is a correlation between glycosylated hemoglobin (HbA1c), a factor recently shown to be useful in predicting GDM, and PlGF. Methods: PlGF was measured at 8-14 weeks with the Kryptor Immunoassay Analyzer (Brahms, Berlin, Germany). Absolute values were converted to multiples of the median using the software provided by the Fetal Medicine Foundation London. GDM was diagnosed using internationally accepted criteria. HbA1c levels were quantified using the TOSOH G7 automated hemoglobin analyzer. Results: From January to December 2014, 328 women were included in the study, 51 (15.5%) of whom developed GDM. First-trimester PlGF quantification does not discriminate between women at risk to develop GDM and controls, while HbA1c is able to do so. No correlation was found between PlGF and HbA1c. Conclusion: Our findings do not lend support to the hypothesis that early PlGF values are different in women who later develop GDM.

Obstetric complications after laparoscopic excision of posterior deep infiltrating endometriosis: a case–control study

OBJECTIVE To study obstetric outcomes and complications in women with previously excised posterior deep infiltrating endometriosis (DIE) in comparison with women without endometriosis. DESIGN Matched case-control study. SETTING Tertiary-level academic center. PATIENT(S) All surgeries for endometriosis performed in the Department of Gynecology and Gynecological Oncology, University of Bern between March 2004 and July 2015, were assessed. Inclusion criteria included complete laparoscopic excision of posterior DIE. Exclusion criteria included concomitant hysterectomies, refusal to participate, and patients lost to follow-up. Each subsequent pregnancy was matched to three controls by maternal age, parity, history of cesarean, and mode of conception. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Obstetric complications. RESULT(S) Among 841 patients with surgically diagnosed endometriosis, 125 satisfied the inclusion and exclusion criteria. Of these, 73 pregnancies resulted, although a further 11 patients were excluded owing to early miscarriages or extrauterine pregnancies. The final study cohort included 62 singleton pregnancies matched to 186 controls. The analysis identified an increased risk of placenta previa, gestational hypertension, and intrauterine growth restriction for the case group. The possibility of successful vaginal delivery was similar between groups. Moreover, no significant increase in risk of maternal and neonatal delivery complications, except for a slightly higher postpartum blood loss in the case group, was observed. CONCLUSION(S) Despite previous surgical excision, women with history of DIE present a higher risk of placenta previa, gestational hypertonia, and intrauterine growth restriction during pregnancy. Previous surgery for DIE does not seem to predispose to failed vaginal delivery.

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

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.

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

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.