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Why Was the Maternal Serum Screening Cut-off Changed?

  • Prenatal Screening Ontario recommended certain temporary measures during the COVID-19 pandemic, to ensure every pregnant individual has access to high-quality prenatal screening during this time.
  • At the onset of the pandemic, there were concerns that pregnant individuals would have reduced access to nuchal translucency ultrasound facilities, and some would therefore miss the time window for enhanced First Trimester Screening. 
  • One of the temporary measures was to change the trisomy 21 cut-off for Maternal Serum Screening (MSS) from 1 in 200 to 1 in 350, in order to bring up the detection rate of the screen to similar levels as enhanced First Trimester Screening. Maternal Serum Screening consists of only a blood test in the second trimester. 

The recommendation has now been put forth by Prenatal Screening Ontario to continue the use of an MSS cut-off of 1 in 350 for trisomy 21 indefinitely, based on the superior sensitivity compared to the 1 in 200 cut-off.

The Impact of BORN Data

The decision to maintain the 1 in 350 cut-off was informed by data from Ontario pregnancies. Real-world data showed the 1 in 350 cut off detects more pregnancies of trisomy 21 than the previous cut-off of 1 in 200.

Performance of Maternal Serum Screening by Cut-Off
Maternal Serum Screening Cut-OffSensitivity
% (95% CI)		Specificity
% (95% CI)		Positive Predictive Value
%(95% CI)		Negative Predictive Value
%(95% CI)		False Positive Rate
%(95% CI)		False Negative Rate
%(95% CI)
1 in 350 86.79
(74.66, 94.52)		 92.12
(91.78, 92.44)
2.23
(1.64, 2.96)
99.97
(99.94, 99.99)		 7.88
(7.56, 8.22)		 13.21
(5.48, 25.34)
1 in 200 S
(61.72, 86.24)*		 94.81
(94.53, 95.08)		 2.92
(2.10, 3.96)		 99.95
(99.91, 99.97)		 5.19
(4.92, 5.47)		 S
(13.76, 38.28)*
 
 Notes
  1. The timeline for these tables was based on singleton pregnancies with an EDD of 01-Sep-2016 to 03-03-2021. 
  2. S = point estimate suppressed when confidence interval >20%.
  3. * = performance data have a confidence interval greater than 20%. These performance metrics were calculated using small cell sizes from the available Multiple Marker Screening and cytogenetic data in the BIS and are subject to change as more data are collected. Please interpret these data with caution.
  4. Outcome data for autosomes screened (chromosomes 21 and 18) were supplemented using data from the BORN information system (BIS) for negative results only, where the outcomes for pregnancies with no cytogenetic outcome were set to test-negative when their corresponding BIS record had no indication for the disorder during the perinatal period.
  5. Uninterpretable, inconclusive, mosaic and partial cytogenetic results were excluded from this cohort. 
  6. The screen-positive cut-off for MSS  for trisomy 21 changed over the timeline of this analysis from 1/200 before April 2020 to 1/350 after April 2020. A screen positive result is defined by whether the result was positive based on the cut-off value established at the time of screening.
 

The screen-positive cut-off for MSS  for trisomy 21 changed from 1 in 200 before April 2020 to 1 in 350 after April 2020. Overall, during the full study timeline (~4.5 years), a cut-off of 1 in 350 throughout this time period would have  detected 6 additional pregnancies with trisomy 21.