Objective
The objective of the study was to determine the value of maternal serum Down syndrome screening in patients affected by renal disease.
Study Design
A study group of 54 pregnant women with renal diseases defined before pregnancy, was compared with a control group of 108 patients matched for maternal age, maternal weight, smoking status, and gestational age. Maternal serum markers (free β-human chorionic gonadotropin [hCG], total hCG, alpha-fetoprotein) expressed in multiple of median and maternal renal function markers (creatinine, β2-microglobulin, α1-microglobulin) were assayed.
Results
The percentage of patients in the Down syndrome at-risk group (>1:250) using free β-hCG was significantly higher ( P < .02) in the renal disease group (48%) than in the control group (12%). No significant difference was observed for total hCG (25% vs 15%).
Conclusion
Down syndrome screening using free β-hCG is not applicable in patients with renal disease whatever the maternal serum creatinine and can be used with caution when total hCG is used.
The usual approach to prenatal screening for Down syndrome (DS) is to estimate a woman’s risk of having a trisomy 21–affected pregnancy on the basis of factors such as maternal age, maternal serum markers, or first-trimester nuchal translucency measurement, using different combinations. Depending on the combinations, 60-90% of fetuses with DS can be detected with a 5% false-positive rate.
Different confounding factors have been evaluated, such as maternal weight, maternal smoking status, twin pregnancies, a previous trisomy 21–affected child, and various adjustments, allow an appropriate screening. However, in patients affected by renal disease, abnormally high human chorionic gonadotropin (hCG) values have been described in case report or small series, but various issues remain unsolved, such as the relative modification of the DS markers, the creatinine cutoff above which DS screening should not be used, and the application of such screening in renal transplant recipients.
The aim of the present study was to firmly establish the limits of DS maternal serum screening in a retrospective series of pregnant women presenting with renal diseases when free β-hCG or total hCG is used.
Materials and Methods
This retrospective study was conducted during the period 2000-2008 in patients who underwent routine second-trimester maternal DS screening. Informed consent was obtained for each patient. Institutional review board approval was obtained for this study (Comité d’Ethique de la Recherche en Obstétrique et Gynécologie 2008-021).
The study group comprised 54 pregnant women with renal disease (RD group). Twin pregnancies were excluded. The control group consisted of 108 serum samples randomly selected from the routine second-trimester maternal serum screening database, matched with the study group based on maternal age, maternal weight, smoking status, and gestational age. For both groups, patients older than 35 years were included, therefore leading to a high false-positive rate of DS risk calculation. Amniocentesis was performed at the parents’ request in 10 patients of the RD group and in 13 of the control group. Fetal karyotyping was normal in all cases. No DS was observed at birth in both groups.
French DS screening policy relies on second-trimester maternal serum marker screening (gestational age between 14 and 18 weeks of amenorrhea) and is strictly regulated. First trimester is actually not available. Routine second-trimester maternal serum screening was based on free β-hCG and alpha-fetoprotein (AFP) (Dualkit, AutoDelfia, Life cycle software; PerkinElmer, Turku, Finland). Results were expressed in multiple of median (MoM). In the present study, 2 DS risks were calculated, 1 based on the combination of DS risk because of maternal age, AFP MoM, and free β-hCG MoM and the other risk using total hCG MoM instead of free β-hCG. A cutoff of 1/250 at sampling was used for both risks.
Of the 54 samples, 44 were available (kept frozen at –40°C), allowing determination of total hCG for DS screening (AutoDelfia; PerkinElmer) and maternal serum markers of renal failure including urea (DiaSys, Condom, France), creatinine (Creatinine-2Enzy; Siemens, Tarrytown, NY), β2-microglobulin (Olympus, Hamburg, Germany), α1-microglobulin (Roche Hitachi, Mannheim, Germany), and total protein (Protein2; Siemens) as a reference marker. When the sample was not available, maternal serum creatinine measured in the month of the serum screening was taken into account.
Renal diseases before pregnancy were defined by proteinuria greater than 0.5 g per 24 hours and/or glomerular filtration rate (GFR) (estimated using the modification of the diet in renal disease [MDRD] formula) less than 60 mL/min. The etiologies of renal diseases were as follows: polycystic renal disease (n = 8); uropathy with reflux (n = 7); glomerulonephritis (n = 6); lupus nephritis (n = 6); Berger disease (n = 4); rheumatoid purpura (n = 4); nephrotic syndrome (n = 4); diabetic nephropathy (n = 3); glomerular nephropathy (n = 2); tubular interstitial granulomatosis nephropathy (n = 3); nephronophthisis (n = 2); nephroangiosclerosis (n = 1); Alport syndrome (n = 1); and unknown (n = 3).
To estimate renal function, guidelines specifically exclude interpretation of the MDRD and Cockroft-Gault formulas in pregnant women; therefore, renal function was evaluated based on serum creatinine using a 125 μmol/L cutoff as proposed by Shemesh et al and Perrone et al. Comparisons were performed using the Mann-Whitney test and χ 2 for percentages.
Results
Table 1 presents the population of the RD group vs the control group for all studied parameters. As expected, no significant difference was observed for matched criteria, and a significant difference was observed for markers of maternal renal failure between the 2 groups.
| Parameters | Renal disease group (n = 54), median (extremes) | Control group (n = 108), median (extremes) | P |
|---|---|---|---|
| Age, y | 31 (23-42) | 31 (23-41) | NS |
| Maternal weight, kg | 62 (45-144) | 61 (42-113) | NS |
| Gestational age at sampling, wks and d | 15.3 (14.1-24.6) | 15.3 (14.1-25) | NS |
| Creatinine, μmol/L | 84 (34-329) | 49 (22-69) | < .0001 |
| Urea, mmol/L | 6 (3.1-12.9) | 3.2 (1.7-5.7) | < .0001 |
| α1-Microglobuline, mg/L | 28.3 (3.9-126.3) | 15.4 (1.2-46) | < .0001 |
| β2-Microglobuline, mg/L | 2.33 (1.24-9.87) | 1.28 (0.96-2.63) | < .0001 |
| Total protein, g/L | 68 (55-79) | 69 (60-88) | NS |
| AFP, MoM | 1.07 (0.44-1.92) | 0.96 (0.41-1.99) | NS |
| Free β-hCG, MoM | 2.13 (0.32-32.8) | 1.04 (0.18-13.3) | < .0001 |
| DS risk calculation, 1/ a | 270 (9-10,000) | 1321 (5-10,000) | < .0001 |
| Total hCG, MoM | 1.40 (0.3-9.5) | 1.10 (0.2-7.1) | .01 |
| DS risk calculation, 1/ b | 1132 (30-10,000) | 1350 (16-10,000) | NS |
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