Routinization of prenatal screening with the non-invasive prenatal test: pregnant women's perspectives.

Due to the favorable test characteristics of the non-invasive prenatal test (NIPT) in the screening of fetal aneuploidy, there has been a strong and growing demand for implementation. In the Netherlands, NIPT is offered within a governmentally supported screening program as a first-tier screening test for all pregnant women (TRIDENT-2 study). However, concerns have been raised that the test's favorable characteristics might lead to uncritical use, also referred to as routinization. This study addresses women's perspectives on prenatal screening with NIPT by evaluating three aspects related to routinization: informed choice, freedom to choose and (personal and societal) perspectives on Down syndrome. Nationwide, a questionnaire was completed by 751 pregnant women after receiving counseling for prenatal screening. Of the respondents, the majority (75.5%) made an informed choice for prenatal screening as measured by the multidimensional measure of informed choice (MMIC). Education level and religious affiliation were significant predictors of informed choice. The main reason to accept screening was "seeking reassurance" (25.5%), and the main reason to decline was "every child is welcome" (30.6%). The majority of respondents (87.7%) did not perceive societal pressure to test. Differences between test-acceptors and test-decliners in personal and societal perspectives on Down syndrome were found. Our study revealed high rates of informed decision-making and perceived freedom to choose regarding fetal aneuploidy screening, suggesting that there is little reason for concern about routinization of NIPT based on the perspectives of Dutch pregnant women. Our findings highlight the importance of responsible implementation of NIPT within a national screening program.

Is asymptomatic bacteriuria associated with short cervical length in women with a singleton pregnancy, a secondary analysis of two national cohort studies with small embedded randomized controlled trials.

OBJECTIVE: To assess the association between asymptomatic bacteriuria (ASB) and short cervical length (CL), since they are both associated with preterm delivery. STUDY DESIGN: In two prospective multicentre cohort studies, pregnant women were screened for the presence of ASB and short CL (≤25 mm). We compared CL in women with and without ASB. Both studies had a small randomised clinical trial embedded. RESULTS: Our study population comprised 1 610 women, of whom 114 were ASB positive. Median cervical length was similar in women with and without ASB (44.0 vs 44.0 mm, P = 0.60). More women in the ASB positive group had a short CL compared to the ASB negative group (1.8 % versus 0.4 %, P = 0.047)). The gestational age at delivery did not differ between the groups (ranging from 38 + 3 in women with ASB and short CL to 39 + 5 in women without ASB with a short CL P = 0.52). No preterm births occurred in women with a short cervical length (regardless of ASB status). In the women without ASB and no short CL 4.8 % had a preterm birth, in the women with ASB but not a short CL 4.1 % had a preterm birth. CONCLUSION: While ASB status did not influence median cervical length, we found a significant relationship between a short CL and ASB positive women. We found no statistical significant difference on the preterm birth rate and mean gestational age.

TRIDENT-2: National Implementation of Genome-wide Non-invasive Prenatal Testing as a First-Tier Screening Test in the Netherlands.

The Netherlands launched a nationwide implementation study on non-invasive prenatal testing (NIPT) as a first-tier test offered to all pregnant women. This started on April 1, 2017 as the TRIDENT-2 study, licensed by the Dutch Ministry of Health. In the first year, NIPT was performed in 73,239 pregnancies (42% of all pregnancies), 7,239 (4%) chose first-trimester combined testing, and 54% did not participate. The number of trisomies 21 (239, 0.33%), 18 (49, 0.07%), and 13 (55, 0.08%) found in this study is comparable to earlier studies, but the Positive Predictive Values (PPV)-96% for trisomy 21, 98% for trisomy 18, and 53% for trisomy 13-were higher than expected. Findings other than trisomy 21, 18, or 13 were reported on request of the pregnant women; 78% of women chose to have these reported. The number of additional findings was 207 (0.36%); these included other trisomies (101, 0.18%, PPV 6%, many of the remaining 94% of cases are likely confined placental mosaics and possibly clinically significant), structural chromosomal aberrations (95, 0.16%, PPV 32%,) and complex abnormal profiles indicative of maternal malignancies (11, 0.02%, PPV 64%). The implementation of genome-wide NIPT is under debate because the benefits of detecting other fetal chromosomal aberrations must be balanced against the risks of discordant positives, parental anxiety, and a potential increase in (invasive) diagnostic procedures. Our first-year data, including clinical data and laboratory follow-up data, will fuel this debate. Furthermore, we describe how NIPT can successfully be embedded into a national screening program with a single chain for prenatal care including counseling, testing, and follow-up.

Preventing Preterm Birth with Progesterone in Women with a Short Cervical Length from a Low-Risk Population: A Multicenter Double-Blind Placebo-Controlled Randomized Trial.

OBJECTIVE: The objective of this study was to evaluate the effectiveness of vaginal progesterone in reducing adverse neonatal outcome due to preterm birth (PTB) in low-risk pregnant women with a short cervical length (CL). STUDY DESIGN: Women with a singleton pregnancy without a history of PTB underwent CL measurement at 18 to 22 weeks. Women with a CL ≤ 30 mm received vaginal progesterone or placebo. Primary outcome was adverse neonatal outcome, defined as a composite of respiratory distress syndrome, bronchopulmonary dysplasia, intracerebral hemorrhage > grade II, necrotizing enterocolitis > stage 1, proven sepsis, or death before discharge. Secondary outcomes included time to delivery, PTB before 32, 34, and 37 weeks of gestation. Analysis was by intention to treat. RESULTS: Between 2009 and 2013, 20,234 women were screened. A CL of 30 mm or less was seen in 375 women (1.8%). In 151 women, a CL ≤ 30 mm was confirmed with a second measurement and 80 of these women agreed to participate in the trial. We randomly allocated 41 women to progesterone and 39 to placebo. Adverse neonatal outcomes occurred in two (5.0%) women in the progesterone and in four (11%) women in the control group (relative risk [RR], 0.47; 95% confidence interval [CI], 0.09-2.4). The use of progesterone resulted in a nonsignificant reduction of PTB < 32 weeks (2.0 vs. 8.0%; RR, 0.33; 95% CI, 0.04-3.0) and < 34 weeks (7.0 vs. 10%; RR, 0.73; 95% CI, 0.18-3.1) but not on PTB < 37 weeks (15 vs. 13%; RR, 1.2; 95% CI, 0.39-3.5). CONCLUSION: In women with a short cervix, who are otherwise low risk, we could not show a significant benefit of progesterone in reducing adverse neonatal outcome and PTB.