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

INTRODUCTION: 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). METHODS: We conducted a nested case-control study comprising 55 women with subsequent preeclampsia, 21 with gestational hypertension, 30 with a small-for-gestational-age infant, and 83 controls. Serum concentrations of hCG-h, proportion of hCG-h to hCG (%hCG-h), PlGF, and sVEGFR-1 were converted to multiples of the medians (MoMs) adjusted for gestational age. RESULTS: Concentrations of hCG-h or %hCG-h did not differ between women with subsequent preeclampsia and controls. In women with subsequent preeclampsia, PlGF was lower (0.62 MoM) than in controls (P < 0.001). In receiver-operating characteristics curve analysis for the prediction of preeclampsia, the area under the curve for hCG-h or %hCG-h was not significantly different from 0.5, whereas that for PlGF was 0.746 (95% confidence interval, 0.656-0.836; P < 0.001). Combining hCG-h or %hCG-h with PlGF did not improve the prognostic value. CONCLUSIONS: Serum hCG-h did not improve prediction of preeclampsia in the second trimester.

The Accu-Chek Mobile blood glucose monitoring system used under controlled conditions meets ISO 15197 standards in the hands of diabetes patients.

BACKGROUND: Self-monitoring of blood glucose is a cornerstone of diabetes management. The aim of this study was to evaluate the analytical quality and the ease of use of the Accu-Chek Mobile, a new glucose monitoring system designed for capillary blood testing by diabetic patients. MATERIALS AND METHODS: The performance of the Accu-Chek Mobile was evaluated both in the hands of a scientist and of diabetes patients. The designated comparative method was a hexokinase-based laboratory method (Architect ci8200). Diabetics (N = 88) with previous experience of self-testing were recruited for the study. Patient samples, containing glucose in concentrations mainly between ˜4 and ˜20 mmol/L, were analyzed in duplicates both on the Accu-Chek Mobile and with the comparative method. The patients answered a questionnaire about the ease of use of the meter. RESULTS: The meter yields reproducible readings, with an imprecision CV <5% as required by the American Diabetes Association (ADA). Of the glucose concentrations obtained by both the scientist and the patients, more than 95% of the individual results were within ± 20% of the comparative method, meeting the ISO 15197 accuracy goal, but not the stricter ± 10% ADA goal. CONCLUSION: Accu-Chek Mobile is a user-friendly glucometer that in a normo- and hyperglycemic range fulfils the ISO 15197 accuracy requirement, also in the hands of diabetes patients.

First trimester biochemistry at different maternal ages.

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 ß-human chorionic gonadotropin (free ß-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.

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 ß-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.

Decreased PAPP-A is associated with preeclampsia, premature delivery and small for gestational age infants but not with placental abruption.

OBJECTIVE: To investigate links between first trimester Down's syndrome screening markers and adverse pregnancy outcomes; preeclampsia (PE), small for gestational age (SGA), preterm delivery (PD) and placental abruption (PA) in spontaneous, chromosomally normal pregnancies. STUDY DESIGN: Cohort study in a university hospital. Data during pregnancy were routinely collected from a total study population of 2844 pregnant women between 2005 and 2007. Four study groups were pregnancies with PE (N=175), PA (N=17), PD (N=213) and SGA (N=275) plus a reference group with normal outcome (N=2164). The median MOMs of maternal serum concentrations of pregnancy associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (fß-hCG) were compared using two-tailed pooled t-tests, continuous variables were compared using Student's two-way t-tests, and Chi-square tests were used to analyse dichotomous variables. Fisher's exact test was used when there were fewer than five units in any of the classes. RESULTS: The median MOM of maternal serum PAPP-A was significantly lower in women with PE, PD and SGA (0.79, 0.80 and 0.79 MOM, respectively) than in the reference group (0.99 MOM) (p<0.01). The median MOM of maternal serum fß-hCG was also significantly lower in the SGA group (0.90 MOM) and in the PE and PD groups (0.86 and 0.92 MOM) than in the reference group (0.99 MOM, p=0.02). There was no detectable difference between the biochemical markers in the PA group and the reference group. No statistical difference was found between NT MOMs in the reference and study groups. CONCLUSION: The concentrations of first trimester screening (FTS) serum markers were lower in pregnancies where PE, PD and SGA occurred. In the latter two cases, there was an inverse association between incidence and PAPP-A and fß-hCG values. However, the development of PA during pregnancy could not be predicted from biochemical marker concentrations. The mechanism behind PA is probably less dependent on the placenta than on the decidua.

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 76949 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 Down's syndrome were analyzed. RESULTS: There was a direct connection between maternal age and the prevalence of Down's 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 Down's syndrome is higher in younger women to achieve the same detection rate. CONCLUSIONS: In combined first trimester screening the risk for Down's syndrome is individual, varying with maternal age. This should be taken into consideration when counseling women.

Increased time-to-pregnancy and first trimester Down's syndrome screening.

BACKGROUND: Time-to-pregnancy (TTP) is a clinical tool used to measure uterine receptivity and a couples' fertility in spontaneously conceived pregnancies. The objective of this study was to examine the effects of TTP on first trimester Down's syndrome (DS) markers in spontaneous, chromosomally normal pregnancies and to compare the results to those in IVF pregnancies. METHODS: A case-control study was conducted amongst patients attending a university hospital in Finland. During 2005-2007 data on pregnant women in Kuopio, with singleton pregnancies, routinely collected by the Department of Obstetrics and Gynaecology of Kuopio University Hospital and Eastern Finland Laboratory Centre were compiled. The data comprised information gathered in first trimester DS screening [age of the mother, serum hCG free beta subunit (fbeta-hCG) and pregnancy-associated plasma protein A (S-PAPP-A) levels and the nuchal translucency (NT) of the fetus], body mass index, method of conception [spontaneous or in vitro fertilization (IVF)], TTP (in spontaneous pregnancies), maternal chronic diseases, smoking habits of the mother, outcome of the pregnancy and prior pregnancy complications. Spontaneous pregnancies were classified into three groups by TTP: 0-12 months (the reference group, N = 1164), 13-24 months (N = 112) and > or = 25 months (N = 70). Screening data from IVF pregnancies (N = 39) were collected for comparison. The size of the total study population was 1385. RESULTS: The median/geometric mean multiple of median (MOM) of S-PAPP-A was significantly lower (P < 0.01) in women with a TTP over 25 months (0.89/0.83 MOM) and in the IVF group (0.95/0.84 MOM) compared with the reference group (1.01/1.03 MOM). However, first trimester S-fbeta-hCG and NT MOMs were not statistically different between the study groups. Consequently, the proportion of DS screening positives was significantly higher in women with TTP > or = 25 months (12.9 versus 2.1%), but not in the IVF group (2.6%). CONCLUSIONS: A TTP of over 2 years altered the levels of DS screening serum markers to levels similar to those observed in IVF pregnancies, with a decrease in PAPP-A levels compared with the reference group. These results raise the possibility that such changes could be related to subfertility rather than to the use of assisted reproductive technology.