Unexpected finding of uniparental disomy mosaicism in term placentas: Is it a common feature in trisomic placentas?

OBJECTIVE: Non-invasive prenatal testing (NIPT) detects placental chromosome aberrations. When amniocentesis reveals a normal karyotype, confined placental mosaicism (CPM) may be assumed. In order to confirm this, placental cytogenetic studies were performed. METHOD: NIPT was conducted in the course of the Dutch TRIDENT study. Placentas of 10 cases with NIPT results indicating an autosomal trisomy and showing a normal (N = 9) or low mosaic karyotype (N = 1) in amniotic fluid (AF) were investigated. The cytotrophoblast as well as the mesenchymal core of two to four placental chorionic villi biopsies were studied with single nucleotide polymorphism (SNP) array. Clinical outcome data were collected. RESULTS: In 10/10 cases, CPM was proven. In 3/10 cases trisomy/uniparental disomy (UPD)/biparental disomy (BPD) mosaicism was discovered. In 2/3 cases, all three cell lines were present in the placenta, whereas BPD was found in AF. In 1/3 cases trisomy 22/UPD22 was present in AF while trisomy 22/BPD22 mosaicism was found in the placenta. Five of 10 pregnancies were affected with pre-eclampsia, low birth weight, preterm delivery, and/or congenital malformations. CONCLUSION: The presence of trisomy/UPD/BPD mosaicism in 3/10 cases that we investigated proves that trisomic zygote rescue may involve multiple rescue events during early embryogenesis. UPD mosaicism, when present in crucial fetal tissues, may explain the abnormal phenotype in undiagnosed cases.

The influence of SNP-based chromosomal microarray and NIPT on the diagnostic yield in 10,000 fetuses with and without fetal ultrasound anomalies.

Prenatal diagnostics has been impacted by technological changes in the past decade, which have affected the diagnostic yield. The aim of this study was to evaluate the impact of SNP array and noninvasive prenatal testing (NIPT) on the diagnostic yield and the number of invasive tests in our center. The frequency of pathogenic fetal unbalanced chromosome aberrations was studied in 10,005 cases referred for prenatal testing in 2009-2015. Chromosomal SNP microarray analysis replaced karyotyping in all invasively tested pregnancies and since 2014 a choice between NIPT and diagnostic testing with microarray was offered to women with an increased risk for common aneuploidy. The introduction of microarray led to an additional yield of submicroscopic pathogenic chromosome aberrations: 3.6% in fetuses with ultrasound anomalies and 1.9% in fetuses without ultrasound anomalies. The introduction of NIPT led to a decrease of invasive tests and of diagnostic yield. Moreover, a diagnostic delay in about 1:350 cases was observed. Since 20%-33% of pathogenic fetal chromosome aberrations are different from the common aneuploidies and triploidy, whole-genome analysis should be offered after invasive sampling. Because NIPT (as a second screening) has led to a decreased diagnostic yield, it should be accompanied by an appropriate pretest counseling.

From Postpartum Haemorrhage Guideline to Local Protocol: A Study of Protocol Quality.

Objective Postpartum hemorrhage (PPH) has a continuously rising incidence worldwide, suggesting suboptimal care. An important step in optimizing care is the translation of evidence-based guidelines into comprehensive hospital protocols. However, knowledge about the quality of these protocols is lacking. The objective of this study was to evaluate the quality of PPH-protocols on structure and content in the Netherlands. Methods We performed an observational multicenter study. Eighteen PPH-protocols from 3 University Hospitals (UH), 8 Teaching Hospitals (TH) and 7 Non-Teaching hospitals (NTH) throughout the Netherlands were acquired. The structure of the PPH-protocols was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE-II) Instrument. The content was appraised using previously developed quality indicators, based on international guidelines and Advance-Trauma-Life-Support (ATLS)-based course instructions. Results The quality of the protocols for postpartum hemorrhage for both structure and content varied widely between different hospitals, but all of them showed room for improvement. The protocols scored mainly below average on the different items of the AGREE-II instrument (8 of the 10 items scored <4 on a 1-7 scale). Regarding the content, adoption of guideline recommendations in protocols was 46 %. In addition, a timely indication of 'when to perform' a recommendation was lacking in three-fourths of the items. Conclusion This study shows that the quality of the PPH-protocols for both structure and content in the Netherlands is suboptimal. This makes adherence to the guideline and ATLS-based course instructions difficult.

Haemorrhage after home birth: audit of decision making and referral. Part 2: Results and discussion.

This descriptive study aims to identify substandard care (SSC) in PPH after home birth in the Netherlands. Sixty seven cases of postpartum haemorrhage (PPH) reported by community-based midwives were collected. After applying selection criteria, seven cases were submitted to audit. The audit panel consisted of 12 midwives (of whom seven contributed a case), 10 obstetricians, an educational expert and an ambulance paramedic. First, an individual assessment was performed by all members. Subsequently, at a plenary audit meeting, SSC factors were determined and assigned incidental, minor or major status. Major SSC was identified in two out of seven cases. We conclude that communication between different healthcare providers should be optimised and a proactive attitude taken to select women who plan to give birth at home, taking into account the possibility of timely referral in case of PPH or retained placenta. National multidisciplinary guidelines on managing obstetric haemorrhage in home birth are urgently needed.

Haemorrhage after home birth: audit of decision making and referral.

In the Netherlands, 20 per cent of women give birth at home. In 0.7 per cent, referral to secondary care because of postpartum haemorrhage (PPH) is indicated. Midwives are regularly trained in managing obstetric emergencies. A postgraduate training programme developed for Dutch community-based midwives called 'CAVE' (pre-hospital obstetric emergency course) focuses on the identification and management of obstetric emergencies, including timely and adequate referral to hospital. This descriptive study aims to identify substandard care (SSC) in PPH after home birth in the Netherlands. Sixty seven cases of PPH reported by community-based midwives were collected. After applying selection criteria, seven cases were submitted to audit. The audit panel consisted of 12 midwives (of which seven contributed a case), 10 obstetricians, an educational expert and an ambulance paramedic. First, an individual assessment was performed by all members. Subsequently, at a plenary audit meeting, SSC factors were determined and assigned incidental, minor and major substandard care.

Major obstetric hemorrhage: Patients' perspective on the quality of care.

OBJECTIVES: Major obstetric hemorrhage (MOH) is the leading cause of severe maternal morbidity and mortality, and can have a significant impact on a woman's life. This study aims to gain insight into the patients reported experiences (PREs) and outcomes (PROs) after a major obstetric hemorrhage, and to investigate which patients are most at risk for negative experiences. MATERIAL AND METHODS: A Consumer Assessment of Healthcare Providers and Systems (CAHPS) based questionnaire was developed covering items on the PREs and PROs, and send to all patients with blood loss exceeding 2500 ml in six hospitals over the period of 2008-2012. A regression analysis was performed to find determinants for negative experiences. RESULTS: In total 372 of the 570 questionnaires were returned. Women scored the overall care before, during and after the MOH with a mean of 7.67, 7.62 and 7.28, respectively. However, most PRE items individually were scored suboptimal, with items regarding information supply scoring the lowest. Our results on the PROs showed 81% of the women (362) sustaining extreme fatigue, whereas problems with concentration (53% of 373 women), memory (49% of 353), or reliving (49% of 356) and irritability (51% of 355) were also frequently endured. Negative long term effects were observed in 28% of the women (106 of 372). We found 'year of the MOH longer ago', 'a lower total blood loss' and 'a large location of birth' to be determinants for negative experiences. CONCLUSIONS: Women frequently reported negative experiences and outcomes following a MOH. Information supply after an MOH concerning both physical and psychological complaints is essential for the improvement of care.

Evaluating Adherence to Guideline-Based Quality Indicators for Postpartum Hemorrhage Care in the Netherlands Using Video Analysis.

OBJECTIVE: To assess adherence to the national postpartum hemorrhage guideline and Managing Obstetric Emergencies and Trauma course instructions and its determinants in the Netherlands. METHODS: A prospective observational multicenter study in 16 Dutch hospitals analyzing data from medical records of 398 women at high risk for postpartum hemorrhage, of which 293 were supplemented with data from prospective video recordings. Adherence to guideline-based quality indicators for prevention, management, and organization of postpartum hemorrhage care was measured. Indicators for prevention and management of postpartum hemorrhage were categorized according to the amount of blood loss (less than 500, greater than 500, greater than 1,000, and greater than 2,000 mL). RESULTS: Overall, a lack of adherence was observed, particularly for the actions to be undertaken with blood loss greater than 1,000 mL (69 patients). Actions were not or only taken in a later stage when the blood loss had already increased to greater than 2,000 mL (21 patients). In almost 41% (n=119/293) of the deliveries, no active management was performed, and in almost 80% (n=89/112), vital signs were not monitored (blood loss greater than 500 mL) or monitored too late with respect to blood loss. The video recordings showed that in general the actual care given was considerably underreported in medical records. Postpartum hemorrhage care in the hospitals was well organized. Fifteen hospitals had a local postpartum hemorrhage protocol, and in 12 hospitals, team trainings were organized. Regarding the determinants, high-risk patient identification and type of hospital (university vs nonuniversity hospital) were mostly associated with better adherence. CONCLUSION: This study showed low adherence to the guideline-based quality indicators, indicating a problem with Dutch quality care. The unique video observations provided additional, valuable information at which level improvement can be made. A tailor-made implementation strategy to improve quality of postpartum hemorrhage care has been developed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00928863.

Prevalence of single and multiple HPV types in cervical carcinomas in Jakarta, Indonesia.

OBJECTIVES: Cervical cancer is the second most frequently occurring type of cancer in women worldwide. A persistent infection with high-risk human papillomavirus (HPV) is a necessary causal factor in cervical carcinogenesis. The distribution of HPV types in populations has been studied worldwide. In Indonesia, however, few data are available describing the prevalence of HPV. Cervical carcinoma is the most common female cancer in Indonesia and causes high morbidity and mortality figures. With HPV vaccination studies in progress, it is important to map the HPV status of a population that would benefit greatly from future prevention programs. METHODS: We tested 74 cervical cancer specimens from consecutive, newly diagnosed cervical cancer patients in the outpatient clinic of the Dr. Cipto Mangunkusumo Hospital, Jakarta. After additional staining, the formalin-fixed, paraffin-embedded tissue samples were histologically classified. HPV presence and genotype distribution were determined by SPF10 polymerase chain reaction and line probe assay. RESULTS: HPV DNA of 12 different HPV types was detected in 96% of the specimens. The three most common types were 16 (44%), 18 (39%) and 52 (14%). In 14% of the specimens, multiple HPV types were present. The multiple HPV types were significantly more prevalent among adenosquamous carcinomas in comparison with squamous cell carcinoma or adenocarcinoma (P = 0.014). CONCLUSIONS: Distribution of HPV types in Indonesia with a more prominent role for HPV 18 is slightly different from that in other parts of the world. The high amount of multiple HPV infections found in adenosquamous carcinomas may prompt further research on the pathogenesis of this type of cervical tumours.