Jaana Marttala

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.

Serum hyperglycosylated human chorionic gonadotrophin at 14-17 weeks of gestation does not predict preeclampsia.

Low first‐trimester serum concentrations of hyperglycosylated human chorionic gonadotrophin (hCG‐h) predict later preeclampsia. We studied whether serum hCG‐h at 14–17 weeks of pregnancy also predicts preeclampsia alone or combined with placental growth factor (PlGF) and soluble vascular endothelial growth factor 1 (sVEGFR‐1).

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.

Prevalence of Down's syndrome in a pregnant population in Finland

The characteristics of the Finnish parturient have changed in recent years. The mean age of mothers at first delivery is now 29.3 years and the number of women > 35 years of age has increased to 19%. This shift has led to an increase in the prevalence of Downs syndrome. Between 1 January 2002 and 31 December 2006, there were 795 cases of Downs syndrome (27/10,000) in the Finnish Register of Congenital Malformations. The distribution of Downs syndrome in terminated pregnancies and newborns was analyzed in 5‐year periods based on maternal age. The distribution of Downs syndrome cases in younger women (< 35 years) and in older women (≥35 years) at the time of delivery was compared. The majority of new Downs syndrome cases occurred in the group having older women (61.1%), even though 35 years is the arbitrary threshold.

Combination of PAPPA, fhCGβ, AFP, PlGF, sTNFR1, and Maternal Characteristics in Prediction of Early-onset Preeclampsia

Objective To evaluate the efficacy of first-trimester markers–-pregnancy-associated plasma protein A (PAPPA), free human chorionic gonadotropin β (fhCGβ), alpha-fetoprotein (AFP), placental growth factor (PlGF), and soluble tumor necrosis factor receptor-1 (sTNFR1) together with maternal characteristics (MC) for prediction of early-onset preeclampsia (EOPE). Methods During 2005-2010, the abovementioned biomarkers were analyzed with logistic regression analysis in 64 EOPE and 752 control subjects to determine whether these biomarkers separately and in combination with MC would predict development of EOPE. Results PAPPA, fhCGβ, and PlGF levels were lower, whereas AFP and sTNFR1 levels were higher in mothers with EOPE compared to controls. The combination of all markers with MC (age, weight, and smoking status) detected 48% of the mothers with EOPE, with a 10% false-positive rate (FPR). Conclusions First-trimester maternal serum levels of PAPPA, fhCGβ, AFP, PlGF, and sTNFR1, together with MC, are predictive of development of subsequent EOPE. These markers, along with MC, form a suitable panel for predicting EOPE.

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.

More invasive procedures are done to detect each case of Down's syndrome in younger women

Objective. To evaluate the performance of first‐trimester combined screening in 5‐year periods according to maternal age in a low‐risk population. Design. A prospective study. Setting: Multicenter study in Finland. Population: A total of 76 949 voluntary women with singleton pregnancies participated in first‐trimester combined screening in public healthcare between 1 May 2002 and 31 December 2008. Methods. The serum samples were analyzed using the PerkinElmer AutoDELFIA® time‐resolved fluoroimmunoassay kit for the measurement of pregnancy‐associated plasma protein‐A and free beta‐human chorionic gonadotropin. Nuchal translucency was measured by trained personnel (midwives or physicians) in a university or central hospital. Main Outcome Measures. Performance, detection rate, false positive rate and the number of invasive procedures needed to detect a single case of Downs syndrome were analyzed. Results. There was a direct connection between maternal age and the prevalence of Downs syndrome with a low prevalence in young women being 1:1 193 in the 25–29 age group and 1:150 in the 35–39 age group. Consequently, for a fixed false positive rate of 5%, the number of invasive procedures needed to detect one case of Downs syndrome is higher in younger women to achieve the same detection rate. Conclusions: In combined first trimester screening the risk for Downs syndrome is individual, varying with maternal age. This should be taken into consideration when counseling women.

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.

Adding ADAM12 in risk calculation program does not improve the detection rate of trisomies 18 and 13 in first trimester screening

Objective: To investigate first trimester levels of ADAM12 in trisomy 18 and 13 pregnancies and whether incorporating ADAM12 in the LifeCycle™ risk calculation program of trisomy 18 and trisomy 13 screenings can improve the detection rates of trisomies 18 and 13. Methods: ADAM12 was incorporated in the LifeCycle™ risk calculation program. A specific algorithm with cut-off of 1:200 for screening of trisomies 18 and 13 was employed. Detection rates for trisomies 18 and 13 were calculated. Results: There was a significant difference in ADAM12 levels between trisomy 18 pregnancies and controls during the gestation weeks 9 + 0 – 10 + 6, but not thereafter. In trisomy 13 pregnancies there was no difference in weeks 9 + 0 – 10 + 6, but there was in 11 + 0 – 12 + 6. The specific algorithms for trisomies 18 and 13 combined with algorithm for trisomy 21 yielded detection rates of 73.7% and 66.7%, respectively. The combined false positive rate was 4.6%. Adding ADAM12, the detection rate for trisomy 18 was the same, at 73.7% and for trisomy 13, at 66.7%. Conclusion: ADAM12 did not improve the detection rate.

First trimester biochemistry at different maternal ages

Abstract Background: The performance of first trimester biochemical screening was compared at different pregnancy weeks and maternal ages during 2002–2008 in a screened population of 76,949 women. Methods: The detection rates, as well as the median multiples of a median (MOMs) of free β-human chorionic gonadotropin (free β-hCG) and pregnancy-associated plasma protein-A (PAPP-A), were compared between completed gestational weeks 8–13 and between different maternal ages separated into 5-year groupings. Results: The number of singleton Down syndrome pregnancies was 221. The median age of the screened women was 30 years and the proportion of women aged ≥35 years 16.9%. The median age of the women with a Down syndrome pregnancy was 37 years. In women aged <35 years, the biochemical markers provided a detection rate of only 38.6%, whereas in women aged ≥35 years, the biochemical markers detected 82.7% of cases (p<0.01). Conclusions: Biochemical screening works best amongst women aged ≥35 years. For younger mothers aged <35 years, combined screening should be the method of choice.