Advertisement

Obesity and cell-free DNA “no calls”: is there an optimal gestational age at time of sampling?

Published:January 29, 2017DOI:https://doi.org/10.1016/j.ajog.2017.01.011

      Background

      Cell-free DNA screen failures or “no calls” occur in 1-12% of samples and are frustrating for both clinician and patient. The rate of “no calls” has been shown to have an inverse relationship with gestational age. Recent studies have shown an increased risk for “no calls” among obese women.

      Objective

      We sought to determine the optimal gestational age for cell-free DNA among obese women.

      Study Design

      We performed a retrospective cohort study of women who underwent cell-free DNA at a single tertiary care center from 2011 through 2016. Adjusted odds ratios with 95% confidence intervals for a “no call” were determined for each weight class and compared to normal-weight women. The predicted probability of a “no call” with 95% confidence intervals were determined for each week of gestation for normal-weight and obese women and compared.

      Results

      Among 2385 patients meeting inclusion criteria, 105 (4.4%) had a “no call”. Compared to normal-weight women, the adjusted odds ratio of a “no call” increased with increasing weight class from overweight to obesity class III (respectively: adjusted odds ratio, 2.31; 95% confidence interval, 1.21–4.42 to adjusted odds ratio, 8.55; 95% confidence interval, 4.16–17.56). A cut point at 21 weeks was identified for obesity class II/III women at which there is no longer a significant difference in the probability of a “no call” for obese women compared to normal weight women. From 8-16 weeks, there is a 4.5% reduction in the probability of a “no call” for obesity class II/III women (respectively: 14.9%; 95% confidence interval, 8.95–20.78 and 10.4%; 95% confidence interval, 7.20–13.61; Ptrend < .01).

      Conclusion

      The cut point of 21 weeks for optimal sampling of cell-free DNA limits reproductive choices. However, a progressive fall in the probability of a “no call” with advancing gestational age suggests that delaying cell-free DNA for obese women is a reasonable strategy to reduce the probability of a “no call”.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Gil M.M.
        • Akolekar R.
        • Quezada M.S.
        • Bregant B.
        • Nicolaides K.H.
        Analysis of cell-free DNA in maternal blood in screening for aneuploidies: meta-analysis.
        Ultrasound Obstet Gynecol. 2015; 45: 249-266
        • Wang E.
        • Batey A.
        • Struble C.
        • Musci T.
        • Song K.
        • Oliphant A.
        Gestational age and maternal weight effects on fetal cell-free DNA in maternal plasma.
        Prenat Diagn. 2013; 33: 662-666
        • Kinnings S.L.
        • Geis J.A.
        • Almasri E.
        • et al.
        Factors affecting levels of circulating cell-free fetal DNA in maternal plasma and their implications for noninvasive prenatal testing.
        Prenat Diagn. 2015; 35: 816-822
        • Palomaki G.E.
        • Kloza E.M.
        • Lambert-Messerlian G.M.
        • et al.
        DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study.
        Genet Med. 2011; 13: 913-920
        • Ashoor G.
        • Poon L.
        • Syngelaki A.
        • Mosimann B.
        • Nicolaides K.H.
        Fetal fraction in maternal plasma cell-free DNA at 11-13 weeks’ gestation: effect of maternal and fetal factors.
        Fetal Diagn Ther. 2012; 31: 237-243
        • Pergament E.
        • Cuckle H.
        • Zimmermann B.
        • et al.
        Single-nucleotide polymorphism-based noninvasive prenatal screening in a high-risk and low-risk cohort.
        Obstet Gynecol. 2014; 124: 210-218
        • Method for estimating due date
        Committee opinion no. 611.
        Obstet Gynecol. 2014; 124: 863-866
        • Mann H.B.
        • Whitney D.R.
        On a test of whether one of two random variables is stochastically larger than the other.
        Ann Math Stat. 1947; 18: 50-60
        • Cuzick J.
        A Wilcoxon-type test for trend.
        Stat Med. 1985; 4: 87-90
        • Norton M.E.
        • Baer R.J.
        • Wapner R.J.
        • Kuppermann M.
        • Jelliffe-Pawlowski L.L.
        • Currier R.J.
        Cell-free DNA vs sequential screening for the detection of fetal chromosomal abnormalities.
        Am J Obstet Gynecol. 2016; 214: 727.e1-727.e6
        • Gregg A.R.
        • Skotko B.G.
        • Benkendorf J.L.
        • et al.
        Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics.
        Genet Med. 2016; 18: 1056-1065
        • Lin C.J.
        • DeRoo L.A.
        • Jacobs S.R.
        • Sandler D.P.
        Accuracy and reliability of self-reported weight and height in the Sister Study.
        Public Health Nutr. 2012; 15: 989-999