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A multicentre study was carried out to determine the frequency and clinical consequences of extremely high maternal serum pregnancy-associated plasma protein (PAPP)-A. There was a total of 79 pregnancies with PAPP-A exceeding 5.0 multiples of the gestation-specific median in a series of 46 776 pregnancies tested (0.2%) at the 7 collaborating centres. Five pregnancies were lost to follow-up, one miscarried and one with Noonan's syndrome was terminated. Of the remaining 72 that ended in a live birth, one infant had gastroschisis and five pregnancies had obstetric complications: pre-eclampsia, pregnancy-induced hypertension, gestational diabetes and two with growth retardation. Among women with high PAPP-A and no complications or adverse outcomes, there was no evidence of a substantial change in the levels of other Down syndrome markers or the extent of nuchal translucency. Three analytical methods were used to assay PAPP-A and yielded different frequencies of extremely high levels (0.05%, 0.4% and 0.6%) possibly owing to cross-reaction with another substance. We conclude that women with high PAPP-A can be reassured that there is no reason to suppose that the outcome of pregnancy will differ from those with normal levels, provided other markers are normal. If, as more centres move their Down syndrome screening practice to the first trimester, additional cases emerge with Noonan's syndrome or gastroschisis and raised PAPP-A, this advice will need to be modified.

The purpose of the present study was to examine screening marker levels in Down syndrome (DS) pregnancies with and without cardiac defects and in euploid pregnancies. Retrospective series in two centers with one or more markers—ultrasound nuchal translucency (NT), first trimester maternal serum pregnancy associated plasma protein (PAPP-A), free-β human chorionic gonadotrophin (free β-hCG), and second trimester serum α-fetoprotein (AFP), unconjugated estriol (uE 3 ), hCG, and free-β hCG. Levels were expressed as multiples of the gestation-specific median (MoM). Differences were assessed by the Wilcoxon rank sum test and 95 % confidence intervals. There were 318 DS pregnancies including 53 (17 %) with cardiac defects. Median NT was higher in cardiac defects (1.82 compared with 1.62 MoM), but not statistically significant ( P = 0.17). Median free β-hCG was significantly highly reduced in the first trimester (1.14 and 2.17 MoM; P < 0.005) and similarly but nonsignificantly in the second trimester (1.59 and 2.32 MoM; P = 0.14). PAPP-A was reduced and AFP increased nonsignificantly with no material differences for uE 3 and hCG. The results on NT and free β-hCG were consistent with a series of 62 euploid pregnancies with cardiac defects screened in one of the centers. The distribution of some markers differs in DS pregnancies with cardiac defects. Depending on the screening protocol, this may affect the phenotype of DS births.

Purpose To investigate additional potential clinical risk factors for preeclampsia. Methods This is a nested case–control study of preeclampsia and unaffected pregnancies. Cases were either from a prenatal screening database or from a national network of clinicians, and controls were from the same prenatal source. Preeclampsia was defined by international criteria which were endorsed by the Ukraine Ministry of Health. Questionnaires were used to record a range of pregnancy related factors, personal history of health conditions and family history, followed by a telephone interview to collect more details. Results There were 103 cases, 56 from the prenatal database and 47 from the clinicians, and 480 controls from the database. The two types of case did not differ in terms of age, weight, BMI or parity. Known risk factors were more common in cases than controls. In addition there was a 17-fold higher prevalence of cholelithiasis in cases compared with controls (29.1% versus 1.7%), a highly statistically significant difference (P < 0.0001). There was also an 8.8-fold increase among the mothers of cases and controls (P < 0.0001), and if either the patient or her mother had the disease the increase was 6.4-fold (P < 0.0001). Including the father or sibling did not increase the relative risk. Conclusion Cholelithiasis is a clinical risk factor for preeclampsia which has not previously been reported. If confirmed by additional studies it may have utility in routine prenatal screening and provide insight into the pathogenesis of preeclampsia.

The most complete information about chromosomal pathology presence in fetuses of thefirst trimester of pregnancy is provided by the use of complex markers: PAPP-A (plasmaprotein-A associated with pregnancy) + free β-hCG (human β chorionic gonadotropin)ultrasound (CP - collar space + nasal bone) for the 10-14th week of development.Purpose of the work – determination of the risk of chromosomal pathology in fetuses inthe first trimester of pregnancy based on markers: biochemical testing of PAPP + freeβ-hCG from the 10-14th week of pregnancy; Ultrasound investigation (US): measurementof the collar space and nasal bone presence.Material and methods: 258 pregnant women with a high risk of chromosomalabnormalities in the first trimester were examined by means of markers: biochemicaltesting of PAPP + free β-hCG and measurements of the collar space. The values ofthe measured markers are expressed as a constituent of the expected median for thecorresponding gestational term. Medians, the 5th and 95th percentiles, percentage outsidethe expected 5th and 95th percentiles, as well as percentage outside the expected 5th /95th percentiles to establish fetal pathology. The study was performed on an ultrasoundscanner Voluson Expert 8 using a transducer with 3-4D transabdominal RAB 4-8D, RAB6-D, and transvaginal RIC 5-9D. Medical Center "EKHOMED" is engaged in expertultrasound envestigations, as well as invasive examinations, which are required for verification of fetal pathology, is the base of Danylo Halytsky Lviv Medical University,DPGE, Department of Radiation Diagnostics.Results. The analysis was carried out in 258 pregnant women with a high risk ofchromosomal abnormalities in the first trimester using markers: biochemical testing ofPAPP + free β-hCG from 10-14 weeks of pregnancy; measurement of the collar spacethickness and visualization or absence of the nasal bone. The pathology is increasedexponentially with the collar space from 0.2% for those fetuses whose thickness isbetween the 5th and 95th centiles, up to 65% for a thickness of 6.5 mm or more. Inthe group of fetuses with chromosomal abnormalities, about 50% have trisomies 21,25% have trisomies 18 or trisomies 13, 10% have Turner syndrome, 5% have triploidy,and 10% have other chromosomal abnormalities. The combination of collar size andPAPP-A and free ß-hCG testing results in a sensitivity of over 90% and a specificity ofover 95%. The rate of false positives is reduced from 3.0% to 2.5%.Conclusions. The thickness of the collar space in chromosomal abnormalities growsexponentially with the thickness of the collar space from 0.2% for those fetuses whosethickness is between the 5th and 95th centile, up to 65% with a collar space thicknessof 6.5 mm or more. In the group of fetuses with chromosomal abnormalities, about 50%have trisomies 21, 25% have trisomies 18 or 13, 10% have Turner's syndrome, 5% havetriploidy, and 10% have other chromosomal abnormalities. The combination of the sizeof the collar space and PAPP-A and free ß-hCG determinations showed a sensitivity ofmore than 90% and a specificity over 95%.