Cell-free DNA methylome analysis for early preeclampsia prediction.

Preeclampsia (PE) is a leading cause for peripartal morbidity, especially if developing early in gestation. To enable prophylaxis in the prevention of PE, pregnancies at risk of PE must be identified early-in the first trimester. To identify at-risk pregnancies we profiled methylomes of plasma-derived, cell-free DNA from 498 pregnant women, of whom about one-third developed early-onset PE. We detected DNA methylation differences between control and PE pregnancies that enabled risk stratification at PE diagnosis but also presymptomatically, at around 12 weeks of gestation (range 9-14 weeks). The first-trimester risk prediction model was validated in an external cohort collected from two centers (area under the curve (AUC) = 0.75) and integrated with routinely available maternal risk factors (AUC = 0.85). The combined risk score correctly predicted 72% of patients with early-onset PE at 80% specificity. These preliminary results suggest that cell-free DNA methylation profiling is a promising tool for presymptomatic PE risk assessment, and has the potential to improve treatment and follow-up in the obstetric clinic.

A cross-country comparison of pregnant women's decision-making and perspectives when opting for non-invasive prenatal testing in the Netherlands and Belgium.

BACKGROUND: The Netherlands and Belgium have been among the first countries to offer non-invasive prenatal testing (NIPT) as a first-tier screening test. Despite similarities, differences exist in counseling modalities and test uptake. This study explored decision-making and perspectives of pregnant women who opted for NIPT in both countries. METHODS: A questionnaire study was performed among pregnant women in the Netherlands (NL) (n = 587) and Belgium (BE) (n = 444) opting for NIPT, including measures on informed choice, personal and societal perspectives on trisomy 21, 18 and 13 and pregnancy termination. RESULTS: Differences between Dutch and Belgian women were shown in the level of informed choice (NL: 83% vs. BE: 59%, p < 0.001), intention to terminate the pregnancy in case of confirmed trisomy 21 (NL: 51% vs. BE: 62%, p = 0.003) and trisomy 13/18 (NL: 80% vs. BE: 73%, p = 0.020). More Belgian women considered trisomy 21 a severe condition (NL: 64% vs. BE: 81%, p < 0.001). Belgian women more frequently indicated that they believed parents are judged for having a child with trisomy 21 (BE: 42% vs. NL: 16%, p < 0.001) and were less positive about quality of care and support for children with trisomy 21 (BE: 23% vs. NL: 62%, p < 0.001). CONCLUSION: Differences in women's decision-making regarding NIPT and the conditions screened for may be influenced by counseling aspects and country-specific societal and cultural contexts.

A nationwide population-based cohort study of peripartum hysterectomy and arterial embolisation in Belgium: results from the Belgian Obstetric Surveillance System.

OBJECTIVES: To assess the prevalence of major obstetric haemorrhage managed with peripartum hysterectomy and/or interventional radiology (IR) in Belgium. To describe women characteristics, the circumstances in which the interventions took place, the management of the obstetric haemorrhage, the outcome and additional morbidity of these women. DESIGN: Nationwide population-based prospective cohort study. SETTING: Emergency obstetric care. Participation of 97% of maternities covering 98.6% of deliveries in Belgium. PARTICIPANTS: All women who underwent peripartum hysterectomy and/or IR procedures in Belgium between January 2012 and December 2013. RESULTS: We obtained data on 166 women who underwent peripartum hysterectomy (n=84) and/or IR procedures (n=102), corresponding to 1 in 3030 women undergoing a peripartum hysterectomy and another 1 in 3030 women being managed by IR, thereby preserving the uterus. Seventeen women underwent hysterectomy following IR and three women needed further IR despite hysterectomy. Abnormal placentation and/or uterine atony were the reported causes of haemorrhage in 83.7%. Abnormally invasive placenta was not detected antenatally in 34% of cases. The interventions were planned in 15 women. Three women were transferred antenatally and 17 women postnatally to a hospital with emergency IR service. Urgent peripartum hysterectomy was averted in 72% of the women who were transferred, with no significant difference in need for transfusion. IR procedures were able to stop the bleeding in 87.8% of the attempts. Disseminated intravascular coagulation secondary to major haemorrhage was reported in 32 women (19%). CONCLUSION: The prevalence in Belgium of major obstetric haemorrhage requiring peripartum hysterectomy and/or IR is estimated at 6.6 (95% CI 5.7 to 7.7) per 10 000 deliveries. Increased clinician awareness of the risk factors of abnormal placentation could further improve the management and outcome of major obstetric haemorrhage. A case-by-case in-depth analysis is necessary to reveal whether the hysterectomies and arterial embolisations performed in this study were appropriate or preventable.

Mutations in CEP120 cause Joubert syndrome as well as complex ciliopathy phenotypes.

BACKGROUND: Ciliopathies are an extensive group of autosomal recessive or X-linked disorders with considerable genetic and clinical overlap, which collectively share multiple organ involvement and may result in lethal or viable phenotypes. In large numbers of cases the genetic defect remains yet to be determined. The aim of this study is to describe the mutational frequency and phenotypic spectrum of the CEP120 gene. METHODS: Exome sequencing was performed in 145 patients with Joubert syndrome (JS), including 15 children with oral-facial-digital syndrome type VI (OFDVI) and 21 Meckel syndrome (MKS) fetuses. Moreover, exome sequencing was performed in one fetus with tectocerebellar dysraphia with occipital encephalocele (TCDOE), molar tooth sign and additional skeletal abnormalities. As a parallel study, 346 probands with a phenotype consistent with JS or related ciliopathies underwent next-generation sequencing-based targeted sequencing of 120 previously described and candidate ciliopathy genes. RESULTS: We present six probands carrying nine distinct mutations (of which eight are novel) in the CEP120 gene, previously found mutated only in Jeune asphyxiating thoracic dystrophy (JATD). The CEP120-associated phenotype ranges from mild classical JS in four patients to more severe conditions in two fetuses, with overlapping features of distinct ciliopathies that include TCDOE, MKS, JATD and OFD syndromes. No obvious correlation is evident between the type or location of identified mutations and the ciliopathy phenotype. CONCLUSION: Our findings broaden the spectrum of phenotypes caused by CEP120 mutations that account for nearly 1% of patients with JS as well as for more complex ciliopathy phenotypes. The lack of clear genotype-phenotype correlation highlights the relevance of comprehensive genetic analyses in the diagnostics of ciliopathies.

Comparison and reproducibility of nuchal translucency measurements using two-dimensional and volume nuchal translucency ultrasound: a prospective study.

OBJECTIVE: To assess the reproducibility and feasibility of automated nuchal translucency (NT) measurement (Volume NT©) in comparison to the two-dimensional (2D) manual approach. The Volume NT technique reveals the correct midsagittal plane automatically and measures the NT at the maximum distance with minimal manipulation. METHODS: In this prospective study, 70 patients underwent NT screening. All standard 2D (standard NT) images and 3D volumes were acquired with an Accuvix V20 Prestige. Off-line measurements of the 3D volumes, manual (manual box NT) and automated (Volume NT) were performed by experienced and nonexperienced operators. Intertechnique and intra- and interobserver agreement were evaluated. RESULTS: Eleven of 70 cases were excluded due to missing data or aberrant position. The Volume NT program was successful in 83.8% of the cases. Acceptable levels of intraobserver agreement were found for all techniques. The Volume NT technique underestimated NT by 0.21 mm (p < 0.0001) in comparison to standard NT. Between-observer agreement for manual box NT was best for the experienced operators. For Volume NT, the results for between-observer agreement were more ambiguous. CONCLUSIONS: The Volume NT program improves standardization of NT measuring. The technique is reproducible and comparable to the 2D manual approach, particularly for inexperienced sonographers. Further technique refinement should reduce any underestimation.

Bilateral Mammary Tuberculosis Associated with a Borderline Ovarian Tumor.

BACKGROUND: Mammary tuberculosis is rare in the Western world. It has no defined clinical or imaging features, and has to be differentiated from breast cancer and an abscess. CASE REPORT: We present a case of mammary tuberculosis combined with borderline ovarian cancer. The bilateral breast tuberculosis was the first and only symptom of underlying tuberculosis with Ziehl-Neelsen-positive para-aortic lymph nodes. During further exploration, an asymptomatic pelvic mass was discovered, which appeared later to be a borderline ovarian tumor. The patient was treated with tuberculostatic therapy for 6 months, resulting in a complete regression of the breast lesions. She also underwent hysterectomy with bilateral salpingo-oophorectomy and lymph node dissection for her ovarian cancer. CONCLUSIONS: This case report emphasizes that breast tuberculosis should be included in the differential diagnosis of any atypical breast mass.

Knowledge of cervix cancer, human papilloma virus (HPV) and HPV vaccination at the moment of introduction of the vaccine in women in Belgium.

AIM: To test the knowledge of women, attending a gynecology clinic, on HPV, cervix cancer awareness and the knowledge and willingness to use HPV vaccine for themselves or their children. SETTING: Routine gynecological and obstetrical care with ambulatory service in a medium-sized general hospital in a small town in Belgium (Heilig Hart Hospital, Tienen). METHODS: Questionnaire to be filled out by 381 consecutive women while in the attendance room for consultation with one of the four gynecologists. Fisher T or Chi(2) were used as statistical methods. RESULTS: Knowledge about HPV as a cause of cervix cancer and the existence of a vaccine was roughly 50%. Women with lower education were more likely to know nothing about the cause of cervix cancer than women with higher education (54 versus 39%, P = 0.016). Half of the women were willing to accept the vaccine, whatever the cost price, and 40% required more information or refunding. Compared to women above 40, young age (25 years or less) was a risk factor for poor knowledge of HPV (P = 0.007), cervix cancer (P = 0.016) and the HPV vaccine (P = 0.07), regardless of a higher degree of education (79% postgraduate degree versus 43.4% in the 40+-year-old women, P = 0.006). Women with a daughter (64.7%) or a son (69.2%) were more inclined to vaccinate their daughter than women without children (46.3%, P < 0.0001). None of the women declined the vaccination because it was meant to protect against a sexually transmitted disease (STD). CONCLUSION: Upon introduction and marketing of the first HPV vaccine, only 50% of women attending a routine gynecology clinic were aware of the role of HPV in cervix cancer and the possibility of getting a vaccination against it. Unexpectedly, despite a high degree of education, young women seem to have a low awareness of cervix cancer, its cause and the preventive measures. Contrary to some women in the USA, Western European women are less likely to decline the HPV vaccine because it will protect them against STD. In Belgium, women who are childless or poorly educated and especially young women should be the targets of campaigns that motivate them to prevent HPV-induced cervix cancer.