Assessment of ß-human-derived chorionic gonadotrophic hormone (ßhCG) and pregnancy-associated plasma protein A (PAPP-A) levels as predictive factors of preeclampsia in the first trimester among Iranian women: a cohort study.

BACKGROUND: Preeclampsia (PE) is a leading cause of maternal and perinatal mortality. There are controversial findings regarding the prediction of PE through the assessment of the Pregnancy-Associated Plasma Protein A (PAPP-A) and ß-Human-Derived Chorionic Gonadotrophic hormone (ßhCG) levels in the first trimester of pregnancy. Therefore, this cohort study was conducted to evaluate of PAPP-A and ßhCG levels as predictive factors for PE development in the first trimester among Iranian women. METHODS: In this cohort study, a total of 4605 volunteer Primigravida and Multigravida women were selected by the census from 16 randomly selected Health Centers in Isfahan, Iran, from July 2016 to June 2018. Eligible pregnant women participated in the study had already undergone fetal anomalies screening tests between 11 + 0 and 13 + 6 weeks of pregnancy and their PAPP-A and ßhCG biomarkers were adjusted to the Multiples of the Median (MOM). MOM PAPP-A <  0.4 and MOM ßhCG > 3 were considered abnormal. The samples were followed up until delivery. The biomarkers' levels were compared in the two groups of women with and without PE and Relative risk (RR) and odds ratio (OR) of PE calculated. RESULTS: In the PE group, the mean MOM PAPP-A was significantly lower (1 vs. 1.09 with P = 0.006) and MOM ßhCG was significantly higher (1.51 vs. 1.14 with P = 0.001) than the group without PE. RR and OR for PE in subjects with MOM PAPP-A <  0.4 were reported as follows: RR = 2.49, (p = 0.001) and OR = 2.09, (p = 0.001). RR and OR for PE in subjects with MOM ßhCG > 3 were also reported as follows: RR = 4.02, (p = 0.001) and OR = 5.65, (p = 0.001). Adjusted OR for MOM PAPP-A <  0.4 and MOM ßhCG > 3 was obtained as follows: OR = 2.09 (P = 0.001) and OR = 5.65 (P = 0.001), respectively. CONCLUSION: The results of the study showed that the high levels of ßhCG would cause 5.65 times increase and the low levels of PAPP-A would cause 2.09 times increase in the chance of developing PE.

Cost and efficacy comparison of prenatal recall and reflex DNA screening for trisomy 21, 18 and 13.

OBJECTIVE: To compare costs and efficacy of reflex and recall prenatal DNA screening for trisomy 21, 18 and 13 (affected pregnancies). In both methods women have Combined test markers measured. With recall screening, women with a high Combined test risk are recalled for counselling and offered a DNA blood test or invasive diagnostic testing. With reflex screening, a DNA analysis is automatically performed on plasma collected when blood was collected for measurement of the Combined test markers. METHODS: Published data were used to estimate, for each method, using various unit costs and risk cut-offs, the cost per woman screened, cost per affected pregnancy diagnosed, and for a given number of women screened, numbers of affected pregnancies diagnosed, unaffected pregnancies with positive results, and women with unaffected pregnancies having invasive diagnostic testing. RESULTS: Cost per woman screened is lower with reflex v recall screening: £37 v £38, and £11,043 v £11,178 per affected pregnancy diagnosed (DNA £250, Combined test markers risk cut-off 1 in 150). Reflex screening results in similar numbers of affected pregnancies diagnosed, with 100-fold fewer false-positives and 20-fold fewer women with unaffected pregnancies having invasive diagnostic testing. CONCLUSIONS: Reflex DNA screening is less expensive, more cost-effective, and safer than recall screening.

First-trimester risk assessment based on ultrasound and cell-free DNA vs combined screening: a randomized controlled trial.

OBJECTIVE: This was a randomized controlled trial to compare risk assessment by first-trimester combined screening (FTCS) with an approach that combines a detailed ultrasound examination at 11-13 weeks' gestation and cell-free DNA (cfDNA) analysis. METHODS: Pregnant women with a normal first-trimester ultrasound examination at 11-13 weeks' gestation (fetal nuchal translucency (NT) ≤ 3.5 mm and no fetal defects) were randomized into one of two groups. In the first group, risk of aneuploidy was assessed using FTCS based on the most recent UK Fetal Medicine Foundation algorithm. In the second group, risk assessment was based on ultrasound findings and cfDNA analysis. An additional tube of blood was collected for FTCS in case the cfDNA analysis was uninformative. Primary outcome was false-positive rate in screening for trisomy 21. A case was considered false positive if the karyotype was not trisomy 21 and if the risk for trisomy 21 was >1:100, irrespective of the method of risk calculation. Results were compared using 95% CIs using the Clopper-Pearson method. RESULTS: Between October 2015 and December 2016, 1518 women with singleton pregnancy underwent first-trimester screening. Thirty-one (2.0%) pregnancies were not eligible for randomization due to increased NT (> 3.5 mm) and/or fetal defect. After exclusion of women who declined randomization (n = 87) and cases of fetal death and loss to follow-up (n = 24), 688 pregnancies were randomized into the FTCS arm and 688 into the ultrasound + cfDNA analysis arm. There were no differences in maternal and gestational age, maternal weight and BMI, ethnicity, use of assisted reproduction and cigarette smoking between the two arms. In the ultrasound + cfDNA analysis arm, median risk for trisomy 21 was 1 in 10 000. None of the cases had a risk above 1: 100 (95% CI, 0.0-0.5%). In the FTCS arm, the median risk for trisomy 21 was 1 in 3787 and in 17 cases, the risk was higher than 1:100, which corresponds to 2.5% (95% CI, 1.5-3.9%) of the FTCS study-arm population. CONCLUSION: Our study has shown that first-trimester risk assessment for trisomy 21 that includes a detailed ultrasound examination as well as NT measurement and is followed by cfDNA testing is associated with a significant reduction in the false-positive rate compared with FTCS. This approach obviates the need for maternal serum free ß-human chorionic gonadotropin and pregnancy-associated plasma protein-A in screening for fetal aneuploidy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Knowledge, understanding, and uptake of noninvasive prenatal testing among Latina women.

OBJECTIVE: The aim of this study is to assess Latina patient understanding of noninvasive prenatal testing (NIPT) and identify what factors influence uptake/refusal to NIPT to adapt counseling to the needs and interests of this population. METHODS: Mixed-methods survey in English and Spanish administered to pregnant Latina patients throughout pregnancy. RESULTS: Sixty-three women participated in our study (67% response rate); 34.9% chose to do NIPT, and 65.1% declined. Approximately half of participants (44%) had an NIPT knowledge score of ≤3 out of six total questions. Two of the most significant factors influencing uptake of NIPT were a higher reported educational level (p = 0.015) and a higher NIPT knowledge score (p = 0.014); 42.9% of participants knew that NIPT only screens for certain chromosomal conditions; 39% of women who declined NIPT would never consider NIPT in the future. CONCLUSIONS: One-third of Latina women elected NIPT; a higher reported educational level and language were most predictive of this choice. Overall knowledge was significantly lower for women who declined NIPT. Lower knowledge may suggest that not all women are making informed decisions because of varying degrees of informed consent. Providing culturally tailored information can help women navigate the complexities of prenatal testing in order to make decisions most aligned with their values.