Sini Peuhkurinen

In combined first-trimester Down syndrome screening, the false-positive rate is not higher in pregnancies conceived after assisted reproduction compared with spontaneous pregnancies

The maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) were reduced in hormonally stimulated pregnancies in the in vitro fertilization and intracytoplasmic sperm injection groups (N=176; PAPP-A: 0.82) and in the entire assisted reproduction group (N=282; PAPP-A: 0.83) as compared with controls (N=24,783; PAPP-A: 0.94). However, the false-positive rate of first-trimester combined screenings was not statistically significantly increased in assisted reproduction pregnancies after adjustment for maternal age.

Low maternal PAPP-A is associated with small-for-gestational age newborns and stillbirths

We investigated the association of first trimester low maternal serum pregnancy‐associated plasma protein‐A (PAPP‐A) levels with small‐for‐gestational age (SGA) newborns and stillbirths (SBs) in a retrospective national population‐based register study. The study group comprised 921 women with the lowest 5% PAPP‐A levels (≤0.3 MoM) and the control group comprising 18,615 women with PAPP‐A levels >0.3 MoM. In the study group there were 35 (3.8%) and in the control group 213 SGA newborns (1.1%), respectively (OR, 3.41; 95% CI, 2.37–4.91). There were 9 (1.0%) and 51 (0.3%) cases of SBs in the study and control groups, respectively (p < 0.002; OR, 3.59; 95% CI, 1.76–7.32). Low PAPP‐A is a risk factor for SGA and SB.

Maternal Serum ADAM12 Levels Correlate with PAPP-A Levels during the First Trimester

Background: We wished to investigate the correlation between a new Down screening marker ADAM12 (a disintegrin and metalloproteinase-12) and pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (fβ-hCG) during the first trimester of pregnancy. Methods: ADAM12, PAPP-A and fβ-hCG were measured in 225 serum samples of randomly chosen pregnancies with completely normal outcome. The samples were taken between pregnancy weeks 9+0 and 12+6. Results: The ADAM12 levels tended to increase with advanced gestational age and the highest levels were detected at pregnancy week 12. The ADAM12 levels correlated with PAPP-A levels. After weight correction and logarithmic transformation the multiples of median (MoM) of ADAM12 still correlated with the MoMs of PAPP-A and also with the MoMs of fβ-hCG. Smokers had lower ADAM12 levels than non-smokers. Conclusion: The secretion of ADAM12 seems to resemble the secretion of PAPP-A in the end of the first trimester. Accordingly ADAM12 appears not to be a separate marker independent of PAPP-A. It remains to be assessed whether adding ADAM12 in Down screening risk calculation will reduce the false positive rate during the first trimester of pregnancy.

Comparison of combined, biochemical and nuchal translucency screening for Down syndrome in first trimester in Northern Finland

To compare the efficacy of fetal nuchal translucency screening, maternal serum screening and combined screening for Down syndrome.

Screening and outcome of chromosomal abnormalities other than trisomy 21 in Northern Finland

Objective. To examine the performance of first‐trimester combined screening after adding the specific algorithms for trisomies 18 and 13 in the Down syndrome screening program for chromosomal abnormalities other than trisomy 21 and to determine the outcomes of such pregnancies. Design. A retrospective study. Setting. Oulu University Hospital, Finland. Population. Pregnant women (n=56 076) participating voluntarily in first‐trimester combined Down syndrome screening in Northern and Eastern Finland during the study period 1 June 2002 to 31 December 2008. Methods. The data of all known cases of chromosomal abnormalities other than trisomy 21 were collected. Main Outcome Measures. Risk algorithms for trisomies 21, 18 and 13 were used for the calculation of patient‐specific risks for certain chromosomal abnormalities. Algorithms were based on maternal age, crown–rump length, nuchal translucency, and measurement of free β‐human chorionic gonadotrophin and pregnancy‐associated plasma protein‐A. Detection rates and false‐positive rates were calculated. Results. A total of 27 cases of trisomy 18, 11 cases of trisomy 13 and 30 cases of other chromosomal abnormalities were analyzed. The algorithm for Down syndrome detected 55.6% of trisomy 18 cases, 36.4% of trisomy 13 cases and 60.0% of other chromosomal abnormalities. When specific risk algorithms were added, the detection rates improved for trisomy 18 (74.0%) and for trisomy 13 (54.5%), with only a slight increase of the false‐positive rate of 0.2%. The detection rate for other chromosomal abnormalities did not improve. Conclusions. Adding the trisomy 18 algorithm to the Down screening program resulted in the detection of five additional trisomy 18 cases.

First trimester Down syndrome screening is less effective and the number of invasive procedures is increased in women younger than 35 years of age

OBJECTIVES We evaluated the performance of first trimester screening for Down syndrome in women less than 35 years of age (study group) and in women aged 35 years or more (control group) in an unselected low-risk population. METHODS The study group comprised a total of 63,945 women who participated in the first trimester combined screening in public health care in Finland during the study period of 1 May 2002 to 31 December 2008. Women at the age of 35 or more (n = 13,004) were controls. Prevalence of Down syndrome, detection rate, false positive rate and number of invasive procedures needed to detect a single case of Down syndrome were analyzed in both groups. RESULTS The overall prevalence of Down syndrome (n = 73) in the study group was 1:876. The number of detected cases was 54. The detection rate was 74.0% with a false positive rate of 2.8%. Number of invasive procedures needed to detect a single case of Down syndrome was 33. In the control group, the detection rate was 87.0% with a false positive rate of 11.9%. The number of invasive procedures needed to detect a single case of Down syndrome was 15. The differences in detection rate and false positive rate were significant, P < 0.012, P < 0.001, respectively. CONCLUSION The overall detection rate given for the entire population is an overestimate for a woman younger than the age of 35, which should be taken into consideration when counselling women of that age.

Combined First-Trimester Screening in Northern Finland: Experiences of the First Ten Years

OBJECTIVE To evaluate the efficacy of first trimester combined screening for Down’s syndrome in Northern Finland during the first 10 years of practice. METHODS During 1 January 2002 to 31 December 2011, 47,896 women participated voluntarily in combined screening during first trimester. The risk cutoff was 1:250. The study period was divided into two time periods; 2002–2006 and 2007–2011. RESULTS During the first half of the study period, the detection rate (DR) was 77.3% with a 4.9% false-positive rate (FPR). During the latter half, the DR was 77.1% with a 2.8% FPR. CONCLUSIONS An important issue is the number of invasive procedures needed to detect one case of Down’s syndrome. The screening performance improved markedly in the latter five years period since the FPR lowered from 4.9% to 2.8% and the number of invasive procedures needed to detect one case of Down’s syndrome lowered from 15 to 11.