First-trimester Combined Screening Test for Aneuploidies in Brazilian Unselected Pregnancies: Diagnostic Performance of Fetal Medicine Foundation Algorithm

Abib, Laila Pinheiro Abi; Sá, Renato Augusto Moreira de; Peixoto-Filho, Fernando Maia

doi:10.1055/s-0038-1666996

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Revista Brasileira de Ginecologia e Obstetrícia

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Sumário

Original Article • Rev. Bras. Ginecol. Obstet. 40 (07) • July 2018 • https://doi.org/10.1055/s-0038-1666996 copy

First-trimester Combined Screening Test for Aneuploidies in Brazilian Unselected Pregnancies: Diagnostic Performance of Fetal Medicine Foundation Algorithm

Rastreio combinado do primeiro trimestre para aneuploidias em gestantes brasileiras não selecionadas: desempenho diagnóstico do algoritmo da Fetal Medicine Foundation

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective

The main objective of this study was to examine the diagnostic performance of the first-trimester combined test for aneuploidies in unselected pregnancies from Rio de Janeiro and compare it with the examples available in the literature.

Methods

We investigated 3,639 patients submitted to aneuploidy screening from February 2009 to September 2015. The examination is composed of the Fetal Medicine Foundation risk evaluation based on nuchal translucency evaluation, mother’s age, presence of risk factors, presence of the nasal bone and Doppler of the ductus venous in addition to biochemical analysis of pregnancy-associated plasma protein A (PAPP-A) and beta-human chorionic gonadotropin (β-hCG) markers. The cut-off point for high risk for aneuploidies was defined as greater than 1:100, with intermediate risk defined between 1:100 and 1:1,000, and low risk defined as less than 1:1,000. The variable aneuploidy was considered as a result not only of trisomy of chromosome 21 but also trisomy of chromosomes 13 and 18.

Results

Excluding the losses, the results of 2,748 patients were analyzed. The firsttrimester combined test achieved 71.4% sensitivity with a 7.4% false-positive (FP) rate, specificity of 92.6%, positive predictive value (PPV) of 6.91% and negative predictive value (NPV) of 99.76%, when the cut-off point considered was greater than 1:1,000. Through a receiving operating characteristics (ROC) curve, the cut-off point that maximized the sensitivity and specificity for the diagnosis of aneuploidies was defined as 1:1,860. When we adjusted the false-positive (FP) rate to 5%, the detection rate for this analysis is 72.7%, with a cut-off point of 1:610.

Conclusion

The combined test of aneuploidy screening showed a detection rate inferior to those described in the literature for a higher FP rate.

Keywords:
chromosomal anomalies; aneuploidy; trisomy 21; nuchal translucency measurement; PAPP-A; β-HCG; pregnancy complications; biomarkers; screen tests on maternal serum

Algorithm Factor	Risk for aneuploidies correlation
Algorithm Factor	Spearman	p
Maternal Age	–0.770	< 0.001
NT	–0.111	< 0.001
Free β-HCG	–0.122	< 0.001
PAPP-A	0.163	< 0.001

Variables and risk for aneuploidy	n	Average	SD	Minimum	Median	Maximum	P-value*
Age (years)
High/intermediate risk	217	37.1	5.5	22.0	38.0	50.0	< 0.001
Low risk	2,531	33.3	4.2	18.0	33.0	49.0	< 0.001
Nuchal translucency (mm)
High/intermediate risk	217	2.04	1.13	0.70	1.80	7.20	< 0.001
Low risk	2,531	1.50	0.47	0.50	1.50	9.00	< 0.001
β-hCG (MoM)
High/intermediate risk	216	1.71	1.40	0.09	1.25	8.34	< 0.001
Low risk	2,529	2.06	24.42	0.01	1.01	933.00	< 0.001
PAPP-A (MoM)
High/intermediate risk	215	0.915	0.702	0.029	0.680	3.964	< 0.001
Low risk	2,499	1.437	0.960	0.108	1.228	9.987	< 0.001

Patient Age	Low risk for aneuploidiesn (%)	Intermediate and high risk for aneuploidiesn (%)	Totaln (%)	Intermediate and high riskPR (CI95%)
≤ 34 years	1,535 (95.6)	71 (4.4)	1,606 (100)	1
35–40 years	892 (92.1)	77 (7.9)	969 (100)	1.8 (1.3–2.5)
≥ 41 years	104 (60.1)	69 (39.9)	173 (100)	9.0 (6.7–12.1)
Total	2,531 (92.1)	217 (7.9)	2,748 (100)

Risk cut-off		Occurrence of aneuploidy				Total		Predictive values
		Yes		No		Total		Positive	Negative
		n	(%)	n	(%)	n	(%)	Positive	Negative
1/100	Positive (> 1/100)	9	(42.9)	53	(1.9)	62	(2.3)	14.52%	99.55%
1/100	Negative (< 1/100)	12	(57.1)	2,674	(98.1)	2,686	(97.7)	14.52%	99.55%
1/1,000	Positive (> 1/1,000)	15	(71.4)	202	(7.4)	217	(7.9)	6.91%	99.76%
1/1,000	Negative (< 1/1,000)	6	(28.6)	2,525	(92.6)	2,531	(92.1)	6.91%	99.76%
1/1,860	Positive (> 1/1,860)	17	(81.0)	390	(14.3)	407	(14.8)	4.18%	99.83%
1/1,860	Negative (< 1/1,860)	4	(19.0)	2,337	(85,7)	2,341	(85.2)	4.18%	99.83%

Criteria defined by plotted ROC curve	Value	Sensibility	Specificity	PPV	NPV
Cut-off point to maximize sensitivity and specificity	1/1,860	90.91%	85.5%	2.46%	99.96%
Fixed FP ratio at 0.5%	1/610	72.7%	95.0%	5.5%	99.88%

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[1] Address for correspondence Renato Augusto Moreira de Sá, PhD, Departamento Materno-Infantil, Universidade Federal Fluminense, Avenida Marques de Paraná, 303 - 2° andar. Centro - Niterói 24033-900, Brazil (e-mail: rsa@cpdt.com.br).