Procedure-related Risk Of Miscarriage Research Articles

Difference in Procedure-Related Risk of Miscarriage between Early and Mid-Trimester Amniocentesis: A Retrospective Cohort Study.

Early amniocentesis (EA)—before 15 gestational weeks—is not recommended because of a high rate of miscarriages. Most studies performed amniocentesis at very early stages of pregnancy (11–13 weeks of gestational age). However, amniocentesis performed at 14 gestational weeks could be an important alternative to mid-trimester amniocentesis (MA) because it shortens the time period between the screening (non-invasive prenatal test (NIPT)) and the diagnostic test (amniocentesis). This study aimed to compare the procedure-related risk of miscarriage between MA (15 + 0 to 17 + 6 weeks of gestational age) and EA (14 + 0–6 weeks of gestational age). This is a multicentric, retrospective cohort study from 1 January 2007 to 21 November 2018, comparing the MA to the EA cohort. Procedure-related fetal loss is defined as spontaneous abortion occurring within 4 weeks of the procedure. Multiple gestations, amniocenteses performed after 17 or before 14 weeks, indications other than prenatal genetic diagnoses and procedures performed by less experienced gynaecologists were excluded. Complete outcome data were available for 1107 out of 1515 women (73.1%): 809 (69.9%) in the MA and 298 (83.2%) in the EA cohort. No significant difference was found (EA 0.82% vs. MA 0.36%; p = 0.646). The difference was 0.46% (odds ratio = 0.673; 95% confidence interval = 0.123–3.699). This study found no significant difference in the procedure-related risk of miscarriage when EA was compared to MA. EA might be considered a safe alternative, though further research is necessary.

The Consequences of Implementing Non-Invasive Prenatal Testing in Dutch National Health Care

Abstract Objective Non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma has been developed for the detection of fetal aneuploidy. Clinical trials have shown high sensitivity and specificity for trisomy 21 (T21) in both high-risk and average-risk populations. Although its great potential for prenatal medicine is evident, more information regarding the consequences of implementing NIPT in a national programme for prenatal screening is required. Study design A decision-analytic model was developed to compare costs and outcomes of current clinical practice in The Netherlands using conventional screening only, with two alternatives: implementing NIPT as an optional secondary screening test for those pregnancies complicated by a high risk for T21, and implementing NIPT as primary screening test, replacing conventional screening. Probability estimates were derived from a systematic review of international literature. Costs were determined from a health-care perspective. Data were analysed to obtain outcomes, total costs, relative costs and incremental cost-effectiveness ratios (ICERs) for the different strategies. Sensitivity analysis was used to assess the impact of assumptions on model results. Results Implementing NIPT as an optional secondary, or as primary screening test will increase T21 detection rate by 36% (from 46.8% to 63.5%) and 54% (from 46.8% to 72.0%), simultaneously decreasing the average risk of procedure-related miscarriage by 44% (from 0.0168% to 0.0094% per pregnant woman) and 62% (from 0.0168% to 0.0064% per pregnant woman), respectively. None of the strategies clearly dominated: current clinical practice is the least costly, whereas implementing NIPT will cause total costs of the programme to increase by 21% (from €257.09 to €311.74 per pregnant woman), leading to an ICER of k€94 per detected case of T21, when utilised as an optional secondary screening test and by 157% (from €257.09 to €660.94 per pregnant woman), leading to an ICER of k€460 per detected case of T21, when utilised as primary screening test. However, implementing NIPT as triage test did result in the lowest expected relative costs per case of T21 diagnosed (k€141). Conclusion NIPT should be implemented in national health care as an optional secondary screening test for those pregnancies complicated by a high risk for T21.

Non-invasive prenatal diagnosis: progress so far

The prenatal diagnosis or exclusion of aneuploidy and single gene disorders has necessitated invasive testing by chorionic villus sampling or amniocentesis. The current use of ultrasound and biochemical markers provides screening but not diagnostic testing for these conditions. The risk of procedure related miscarriage is well recognized, along with the physical discomfort and the mental anguish many couples experience when deciding whether to accept the offer of invasive testing. For these reasons, the ‘holy grail’ of prenatal diagnosis has been to find non-invasive techniques which avoid these risks and discomfort. During the 1990s considerable effort was expended on the isolation of the small number of fetal cells reaching the maternal systemic circulation during pregnancy. This proved to be quite a challenge; fetal erythroblasts and trophoblasts could indeed be found after very significant enrichment and complex sorting protocols, but isolating a pure source was very challenging and anyway concerns existed that some of these fetal cells might have persisted from a previous pregnancy. One of the constituents of maternal plasma is cell free DNA (cfDNA), derived mostly from maternal white blood cells. In 1997, Lo proved that in pregnant women, some of the cfDNA in maternal blood was derived from the feto-placental unit and named this cell free fetal DNA (cffDNA). Y-chromosomal DNA could be reliably identified in the blood of pregnant women carrying a male fetus from as early as the first trimester, using targeted PCR reactions. Women carrying a female fetus should have no Y-chromosomal DNA circulating in their blood, and these Y-specific PCR reactions would in this case fail to produce a product. His work also showed that this cffDNA is cleared from the circulation within a couple of hours of the birth of the baby. Trophoblasts are the mostly likely source of this DNA, and it is also clear now that fetally derived cell free mRNA is also present in maternal plasma. cffDNA accounts for between 3 and 6% of all cfDNA in maternal blood and with very sensitive PCR reactions can be detected as early as 4 weeks’ gestation. Since 1997 significant advances in molecular biology have brought non-invasive prenatal diagnosis (NIPD) to a point where it is now in common use in a small number of defined prenatal situations. However, the next 5e10 years will see it being utilized ever more widely, and probably even in the prenatal testing for common aneuploidies. The first non-invasive techniques using cffDNA relied on the identification of genes or alleles that are not present in the mother but are present in the baby, either because they have been

Prenatal diagnosis for multiple pregnancies

In multiple pregnancies, first trimester ultrasound is crucial to diagnose chorionicity, to detect major structural defects, and to screen for chromosomal abnormalities based on nuchal translucency measurement. The efficacy of nuchal translucency measurement screening in twins might be improved when combined with first trimester maternal serum screening. In twins as in singletons, the risk of fetal loss attendant to chorionic villi sampling and to amniocentesis are similar. When an invasive procedure is indicated in twins, chorionic villi sampling has, over amniocentesis, the advantage of allowing selective termination to be performed in the first trimester, when the procedure related risk of miscarriage is minimal. It has the disadvantage of leading to ambiguous results in up to 2% of cases. While chorionic villi sampling is the choice technique in pregnancies at very high risk, amniocentesis is still indicated in cases at more moderate risk. In monochorionic pregnancies, selective termination can now be performed using a variety of techniques including bipolar or monopolar cord coagulation, and, in acardiac twins, alcohol ablation. However, selective termination remains more hazardous in monochorionic than in dichorionic pregnancies. The outcome of the twin-to-twin transfusion syndrome has been substantially improved by laser photocoagulation of placental shunts and by amniodrainage, but randomized trials are needed to establish the optimal therapeutic strategy, and further pathophysiologic research might result in new treatments.