Trimester Serum Markers Research Articles

Usefulness of early morphological ultrasound in association with cell-free DNA testing in case of atypical serum markers in first trimester of pregnancy: A retrospective study over 5 years

BackgroundEarly morphologic ultrasound, generally carried out in case of atypical first trimester serum markers (PAPP-A and/or free hCGβ <0.30 MoM), has not been re-evaluated since the possibility of performing a cell-free fetal DNA analysis in this indication. Our objective was to evaluate the usefulness of early morphological ultrasound in case of atypical profile of serum markers performed in association with Non-Invasive Prenatal Testing (NIPT). MethodsThis was a single-center retrospective study in a tertiary maternity. Between January 2017 and December 2021, women with an atypical first trimester serum markers and low/intermediate risk for trisomy 21 (<1/50) were included. The clinical data, results of first trimester serum markers, NIPT, early morphological ultrasound and subsequent ultrasounds and other investigations (amniocentesis, pregnancy outcomes) were analyzed. ResultsAfter exclusion of women with high-risk of trisomy 21 and lost to follow-up, 163 women were included. In 72 % of cases (117/163), women had a low risk of trisomy 21, and 39 % (59/163) had an early morphological ultrasound. Early morphological ultrasound was useful to detect severe IUGR leading to the suspicion of triploidy (3/163, 1.8 %). In all other situations, it did not allow earlier management. After analysis of the 3 triploidy cases, a collapsed profile for both serum markers was demonstrated (<0.25 MoM). ConclusionsSystematic early morphological ultrasound in case of an atypical serum marker profile seems useless considering the performance of NIPT. An ultrasound restricted to women with both markers below 0.25 MoM would allow the early detection of triploidy.

VP26.08: Vein of Galen aneurysmal malformation

Vein of Galen aneurysmal malformation is a rare complex malformation of the cerebral vascular system, characterised by the dilation of an embryonic vein precursor of the Galenian vein causing an arteriovenous shunt. It is developed in the embryonic period, sporadic, more common for male fetus. This vascular malformation is detected only half of times before birth, it often increases in size with advancing age and is associated with hydrocephalus, seizures, intracranial hemorrhage, heart failure and even resultant death. So early diagnosis and treatment is important in order to avoid such consequences. We report the case of a 31-year-old pregnant woman of 26 weeks, primiparous, with no obstetric or personal family history of interest. We found, at the second trimester morphological ultrasound, a cerebral vascular dilatation using the colour and pulsed Doppler which was isolated with no other cerebral or other organ malformations. First trimester ultrasound and serum markers were normal. Subsequently, a magnetic resonance was performed confirming the diagnosis. the pregnancy was carried to term with delivery by Caesarean section. Physical examination of the baby was unremarkable. The baby was called for post-natal evaluation at the radiology department on the second day and was scheduled for radiological embolisation of the aneurysm, the newborn died after that intervention. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Association between blastocyst morphology and maternal first trimester serum markers in ongoing pregnancies obtained after single fresh blastocyst transfer

ObjectiveIs there an association between blastocyst morphology and maternal first trimester serum markers in In Vitro Fertilization (IVF) pregnancies obtained after fresh single blastocyst transfer? Study designThis bi-centric retrospective study was conducted between January 2012 and August 2018. We included 122 women aged from 18 to 43 years-old, whose pregnancy progressed at least beyond 13 weeks after a single blastocyst transfer and who participated in the first trimester combined screening test. Day 5 and day 6 blastocysts were evaluated according to Gardner and Schoolcraft classification. Patients were classified into three groups according to blastocysts morphological quality: excellent (≥ 3AA), good (3-6AB, 3-6BA, B2), and medium to poor (3-6BB, 3-6AC, 3-6CA, B1, 3-6CB, 3-6BC). First trimester serum markers were measured in maternal blood between 9 and 11 + 6 gestational weeks. Univariate and multivariate analyses were performed. ResultsFemale body mass index, smoking status, type of infertility, geographical origin, anti-mullerian hormone level, ovarian stimulation characteristics, pregnancy outcomes and obstetrical complications were comparable between the three groups. Patient’s age was not distributed evenly across groups, with women in group “Medium to Poor” appearing to be slightly younger than in other groups. There were no significant differences in mean first trimester serum markers between the three groups (PAPP-A: excellent: 1.23 ± 0.59 MoM; good: 1.45 ± 0.71 MoM; medium to poor: 1.22 ± 0.52 MoM; p = 0,20; free beta-HCG: excellent: 1.66 ± 1.38 MoM; good: 1.19 ± 0.76 MoM; medium to poor: 1.81 ± 1.34 MoM; p = 0,12). No significant difference was found either between mean first trimester serum markers and inner cell mass morphology (PAPP-A: grade A: 1.23 ± 0.58 MoM; grade B: 1.26 ± 0.60 MoM; medium to poor: 1.64 ± 0.87 MoM; p = 0,67 ; free beta-HCG: grade A: 1.66 ± 1.36 MoM; grade B: 1.52 ± 1.10 MoM; medium to poor: 1.57 ± 0.39 MoM p = 0,60), trophectoderm cells morphology (PAPP-A: grade A: 1.25 ± 0.63 MoM; grade B: 1.26 ± 0.51 MoM; medium to poor: not comparable; p = 0,66; free beta-HCG: grade A: 1.60 ± 1.34 MoM; grade B: 1.69 ± 1.14 MoM; medium to poor: not comparable; p = 0,25), or blastocoel expansion (PAPP-A: B1: 1.08 ± 0.51MoM; B2: 1.57 ± 0.70 MoM; B3: 1.26 ± 0.61 MoM; B4: 1.28 ± 0.62 MoM; B5: 1.04 ± 0.38 MoM; p = 0,22; free beta-HCG: B1: 2.01 ± 1.88 MoM; B2: 1.07 ± 0.49 MoM; B3: 1.43 ± 0.87 MoM; B4: 1.68 ± 1.28 MoM ; B5: 1.82 ± 2.03 MoM; p = 0,48).After adjustment on potential confounding factors (female age, type of gonadotropin, parity, number of oocytes retrieved and occurrence of ovarian hyperstimulation syndrome), we did not observe any association between PAPP-A or free beta-HCG levels and blastocyst morphology. ConclusionOur study concluded that first trimester serum markers were not associated with blastocyst morphological characteristics. Although this needs further confirmation, this suggests that blastocyst morphology would not have an impact on placentation. Therefore, these findings are reassuring for couples undergoing IVF and blastocyst transfer.

Prediction of Preeclampsia in Nulliparous Women according to First Trimester Maternal Factors and Serum Markers

Objective: To evaluate the performance of maternal risk factors (BMI and mean arterial pressure [MAP]) and first-trimester maternal serum markers in the early prediction of preeclampsia (PE) in nulliparous women. Material and Methods: This was a case-cohort study based on a cohort of 14,207 nulliparous women. A total of 213 cases with term PE (from 37 weeks + 0 days) and 55 cases with preterm PE (before 37 weeks + 0 days) were identified and validated. Randomly, 449 controls were selected. Serum samples previously collected for the double test (pregnancy-associated plasma protein A [PAPP-A] and free β human chorionic gonadotrophin [hCGβ]) as part of the first-trimester screening program were retrieved and analyzed for placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and neutrophil gelatinase-associated lipocalin (NGAL). Concentrations were transformed to multiples of the median (MoM). Multivariate regression analysis was used for prediction models. Receiver-operating characteristics (ROC) curves were used for evaluation of the screening performance. Results: In preterm PE, the PlGF (0.79 MoM), sFlt-1 (0.86 MoM), NGAL (1.15 MoM), and PAPP-A (0.89 MoM) medians were significantly altered. In term PE, PlGF (0.90 MoM) and NT-proBNP (0.86 MoM) medians were significantly reduced. The combination of MAP and PlGF yielded a 39% detection rate of preterm PE for a 10% false-positive rate. The combination of MAP, BMI, and PlGF yielded a 33% detection rate of term PE with a 10% false-positive rate. Conclusion: First-trimester MAP, maternal serum PlGF, and NGAL are markers of preterm PE. Maternal serum sFlt-1 is a significant marker of preterm PE, but only early in the first trimester. First-trimester maternal serum NT-proBNP is not a predictor of PE. Screening performance for PE with these markers individually or in combination is modest.

Normative Values of Second-Trimester Maternal Serum Markers Using an Automated Assay Platform for Down Syndrome Screening

Objective: Automated chemiluminescent immunoassay has several advantages over manual ELISA with comparable test performance. Few studies have reported the reference values of the second-trimester serum markers maternal serum alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), unconjugated estriol (uE3), and inhibin A (Inh A) by automated immunoassay in Asian population. Accordingly, this study aimed to determine the median values of second trimester serum markers as a function of gestational age (GA) in Thai population using an automated immunoassay. Methods: This prospective cross-sectional study of serum markers in healthy singleton second trimester (14-22 weeks) pregnant women was conducted at Siriraj Hospital from September 2012 to April 2015. Maternal serum AFP, hCG, uE3, and Inh A were analyzed by automated immunoassay. Predicted median values as a function of GA were calculated from best-fit regression equations. Results: A total of 1,526 women were included. Median values serum markers were constructed from the following optimal models: AFP (ng/mL) = 99.082 - 14.195 GA + 0.662 GA 2 , r 2 =0.995; hCG (mIU/mL) = 39, 0168.106 - 35 968.397GA + 876.708GA 2 , r 2 =0.972; uE3 (ng/mL) = -3.388 + 0.274 GA, r 2 =0.997; and, Inh-A (pg/mL) = 1,206.875 - 114.171 GA + 3.174 GA 2 , r 2 =0.882. Using the same platform analysis and maternal weight adjustment, the reference values in Thai population were shown to be different from those of other ethnicities. Conclusion: Median values of second-trimester serum markers for Thai population were determined. Maternal weight and the use of population-specific normal values have to be taken into account for Down syndrome screening in the second trimester.

195: Are women with abnormal 1st and 2nd trimester serum screening markers at risk for recurrence for the same or other abnormal markers in a subsequent pregnancy?

Abnormal 1st and 2nd trimester (1T, 2T) serum markers used for aneuploidy screening are associated with other adverse pregnancy outcomes. Limited data exist on recurrence risks for elevated 2T alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG), but no such data exist for low 1T pregnancy associated plasma protein A (PAPP-A) and HCG or high 2T inhibin and low estriol. Whether women with one abnormal biomarker are at risk for a different abnormal biomarker in a subsequent pregnancy is unknown. We sought to determine the relative risks (RR) of recurrence in the next pregnancy of low PAPP-A (<0.5 MoM) and HCG (<0.5 MoM) in the 1T, and high AFP (>2.5 MoM), HCG (>3.0 MoM), inhibin (>2.0 MoM) and low estriol (<0.5 MoM) in the 2T. Using a database of 14,349 serum markers, we identified 1969 patients with 2 consecutive pregnancies screened during the 1T and 2T for AFP, PAPP-A, HCG, inhibin, and estriol, between 1/2007-12/2016. We compared women with a normal vs abnormal serum marker in the initial pregnancy to determine the rates and RR of an abnormal value for that same marker or a different abnormal marker in the subsequent pregnancy. Chi squared or Fisher's exact tests were used as appropriate. For each serum marker analyzed, we found a statistically significant increased risk for having an abnormal level in the 2nd pregnancy after having an abnormal level in the 1st. Incidence of an abnormal marker in the 1st pregnancy and RR of recurrence are shown in Table 1. There was no association between abnormal PAPP-A in the 1st pregnancy and elevated AFP or HCG in the 2nd pregnancy. Similarly, there was no association between high AFP and abnormal PAPP-A or HCG in the 2nd pregnancy. Abnormal PAPP-A, HCG, AFP, inhibin, and estriol are associated with increased risk of adverse outcomes such as preeclampsia and IUGR. Our results show that patients with an abnormal marker in their 1st pregnancy are at an increased risk for the same abnormal marker in the next pregnancy. Our findings suggest that biomarkers may be indicative of underlying maternal pathophysiology potentially driven by genetic or environmental factors. Additional studies are needed to further investigate the maternal pathophysiologic mechanisms leading to these adverse outcomes which may identify opportunities for therapeutic intervention.

First and second trimester serum tests with and without first trimester ultrasound tests for Down's syndrome screening.

Down's syndrome occurs when a person has three copies of chromosome 21 (or the specific area of chromosome 21 implicated in causing Down's syndrome) rather than two. It is the commonest congenital cause of mental disability. Non-invasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing. Before agreeing to screening tests, parents need to be fully informed about the risks, benefits and possible consequences of such a test. This includes subsequent choices for further tests they may face, and the implications of both false positive (i.e. invasive diagnostic testing, and the possibility that a miscarried fetus may be chromosomally normal) and false negative screening tests (i.e. a fetus with Down's syndrome will be missed). The decisions that may be faced by expectant parents inevitably engender a high level of anxiety at all stages of the screening process, and the outcomes of screening can be associated with considerable physical and psychological morbidity. No screening test can predict the severity of problems a person with Down's syndrome will have. To estimate and compare the accuracy of first and second trimester serum markers with and without first trimester ultrasound markers for the detection of Down's syndrome in the antenatal period, as combinations of markers. We conducted a sensitive and comprehensive literature search of MEDLINE (1980 to 25 August 2011), Embase (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), the Database of Abstracts of Reviews of Effectiveness (the Cochrane Library 25 August 2011), MEDION (25 August 2011), the Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (25 August 2011), the National Research Register (Archived 2007), and Health Services Research Projects in Progress database (25 August 2011). We did not apply a diagnostic test search filter. We did forward citation searching in ISI citation indices, Google Scholar and PubMed 'related articles'. We also searched reference lists of retrieved articles SELECTION CRITERIA: Studies evaluating tests of combining first and second trimester maternal serum markers in women up to 24 weeks of gestation for Down's syndrome, with or without first trimester ultrasound markers, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection. Data were extracted as test positive/test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS criteria. We used hierarchical summary ROC meta-analytical methods to analyse test performance and compare test accuracy. Analysis of studies allowing direct comparison between tests was undertaken. We investigated the impact of maternal age on test performance in subgroup analyses. Twenty-two studies (reported in 25 publications) involving 228,615 pregnancies (including 1067 with Down's syndrome) were included. Studies were generally high quality, although differential verification was common with invasive testing of only high risk pregnancies. Ten studies made direct comparisons between tests. Thirty-two different test combinations were evaluated formed from combinations of eight different tests and maternal age; first trimester nuchal translucency (NT) and the serum markers AFP, uE3, total hCG, free βhCG, Inhibin A, PAPP-A and ADAM 12. We looked at tests combining first and second trimester markers with or without ultrasound as complete tests, and we also examined stepwise and contingent strategies.Meta-analysis of the six most frequently evaluated test combinations showed that a test strategy involving maternal age and a combination of first trimester NT and PAPP-A, and second trimester total hCG, uE3, AFP and Inhibin A significantly outperformed other test combinations that involved only one serum marker or NT in the first trimester, detecting about nine out of every 10 Down's syndrome pregnancies at a 5% false positive rate. However, the evidence was limited in terms of the number of studies evaluating this strategy, and we therefore cannot recommend one single screening strategy. Tests involving first trimester ultrasound with first and second trimester serum markers in combination with maternal age are significantly better than those without ultrasound, or those evaluating first trimester ultrasound in combination with second trimester serum markers, without first trimester serum markers. We cannot make recommendations about a specific strategy on the basis of the small number of studies available.

Do triple test results predict risk for neonatal hyperbilirubinemia?

Objective:Neonatal jaundice is the most common condition that requires hospital admission and outpatient follow-up after discharge in neonates. The values of more than 17 mg/dL in term infants are accepted as neonatal significant hyperbilirubinemia. We aimed to define if there is any relationship between second trimester serum markers and neonatal severe hyperbilirubinemia to protect the neonates from its neurological damage.Methods:Total 1372 pregnant women were enrolled who had done triple test between April 2014 and 2015 and then given birth at our hospital. Our primary outcome was neonatal significant hyperbilirubinemia.Results:The mean age of our study population was 27.9±5.6. A total of 59 patients had babies with neonatal hyperbilirubinemia after exclusion of Rh incompatibility. We detected that the presence of in vitro pregnancy, maternal health problems or poor obstetric history had no effect on the risk for neonatal hyperbilirubinemia. Neonatal hyperbilirubinemia was related with low E3 levels. The ratios of AFP/E3 and hCG/E3 were the most helpful to predict the neonatal hyperbilirubinemia.Conclusions:According to our results, low E3 levels in the triple test result can be helpful to predict the development of the neonatal hyperbilirubinemia. However, this is a bit expensive and many developing countries may not afford it.

EP17.03: First trimester serum markers to predict pregnancy complications: Tunisian prospective study

EP17.03: First trimester serum markers to predict pregnancy complications: Tunisian prospective study

Prediction of Placenta Abrubtion without Risk Factors [Risk Faktoru Olmadan Meydana Gelen Plasenta Dekolmani Onceden Ongorulebilir mi?

Many studies in the literature have shown the assosiation between serum analits of first and second trimester screening test with intra uterin growth retardation and abrubtio placenta.However these markers role in the predicting of placental abrubtion is unclear. We aimed in this study,is there any relationship between placental abrubtion without risk factors and first and seconder trimester screening markers. 120 term pregnant women who gave birth by Caesarean section has been included in this retrospective study, patients and controls were compared for the 1st and 2nd trimester serum markers levels. Fetal nuchal translucency measurements were significantly higher in the study group than control group. This study emphasizes that increased fatal nuchal transluency is more important than serum biomarkers of first and second trimester screening tests.

First trimester serum tests for Down's syndrome screening.

First trimester serum tests for Down's syndrome screening.

First trimester biochemical markers in twin pregnancies

Our aim was to investigate the first trimester serum markers and nuchal translucency (NT) measurements in twin pregnancies in our population. We reviewed the results of all double tests that were performed in our hospital over a three-year period. Out of them, we selected all twins and compared them with a group of three times as many singleton controls. NT measurements and the first trimester serum markers from 49 twin pregnancies were compared to those of 147 pregnant women with normal singleton pregnancy There were no statistically significant differences in age, gestational age and maternal weight between the two groups (p > 0.05). We found similar NT measurements in the two groups. The median MoM of Pregnancy-Associated Plasma Protein A (PAPP-A) and fβ-hCG levels in twins were statistically significantly higher than those in singleton pregnancies. Twelve percent of the twins (12.2%) were the result of assisted reproduction technologies. IVF versus naturally conceived pregnancies showed similar MoM of PAPP-A (2.2 vs. 1.2, respectively) and fβ-hCG (Mann-Whitney U; p = 0.195 and p = 0.958). Our study revealed that median PAPP-A and fβ-hCG levels for twins were less than twice those of singleton values.

259: Evaluation of a cumulative first trimester characteristic and serum marker risk score for predicting early spontaneous preterm birth

259: Evaluation of a cumulative first trimester characteristic and serum marker risk score for predicting early spontaneous preterm birth

First and second trimester maternal serum markers in pregnancies with a vanishing twin.

The aim of this study was to assess the concentration of the first and second trimester maternal serum markers in pregnancies with a vanishing twin. This is a retrospective case-control study of pregnancies screened for Down syndrome in one Ontario center. Singleton pregnancies with ultrasound evidence of a vanishing twin were identified, and each was matched with five normal singleton controls for ethnicity, maternal age, gestational age, and blood sampling date. The median MoM of the first and second trimester serum markers was compared between cases and controls. The differences were assessed using the Mann-Whitney U-test. The study included 174 pregnancies that had a vanishing twin. Compared with control pregnancies, pregnancy associated plasma protein A increased by 21% (p = 0.0026), alpha-fetoprotein (AFP) increased by 10% (p < 0.0001), and dimeric inhibin A (DIA) increased by 13% (p = 0.0470) in pregnancies with a vanishing twin. Unconjugated oestriol and total human chorionic gonadotrophin were not significantly changed in these pregnancies. Pregnancy associated plasma protein A is not an adequate marker for pregnancies with a vanishing twin. The impact of elevated AFP on risk estimation is offset by that of DIA to certain extent. Further studies are needed to establish an adequate adjustment method for AFP and DIA to improve the accuracy of screening results for these pregnancies.

Use of first or second trimester serum markers, or both, to predict preeclampsia.

Preeclampsia is a serious complication of pregnancy, threatening fetal and maternal health. The aim of our study is to examine the association between preeclampsia and biochemical markers, in matched first and second trimester maternal serum samples. This is a nested case/control study derived from the cohort of pregnancies delivering at Women & Infants Hospital. Cases were identified at a clinic or by hospital codes, and individually confirmed by record review. Stored samples were available from 'integrated' Down syndrome screening. Results were expressed as multiples of the median (MoM). Preeclampsia was classified as early/severe, late/severe, or mild based on professional guidelines. An additional adverse outcome group had only gestational hypertension. Ninety-eight cases were each matched with five control pregnancies. Population distribution parameters and within and between trimester correlations were derived for cases and controls for six markers, as well as in case subgroups. The strongest associations were for early/severe preeclampsia with second trimester PAPP-A (rank sum test 2.30, p<0.01); PlGF (2.60, p<0.05) inhibin A (4.45, p<0.05) and endoglin (4.25, p<0.05). No strong associations were found for sVEGF-R and FLRG. Second trimester associations were stronger than those in the first (e.g., PAPP-A 2.45, p<0.01). No between-trimester associations were found that would provide important improvements in prediction. This matched analysis of the serum markers in early pregnancy allows for direct comparison of first and second trimester associations with preeclampsia. PAPP-A and PlGF are equally and highly predictive of early/severe preeclampsia.

First trimester screening cannot predict adverse outcomes yet.

The use of first trimester screening to detect aneuploidy has become an integral part of prenatal care. The application of similar screening algorithms to identify women at the highest risk for other adverse pregnancy outcomes in the first trimester could potentially have a major clinical impact. There has been much investigation into the ability to identify patients early in pregnancy at high risk for adverse pregnancy outcomes who may benefit from further surveillance and/or intervention. For this to be the case, however, as is true of any useful screening test, effective interventions need to be available. Unfortunately, for fetal growth restriction and stillbirth, no such interventions exist short of delivery. For preeclampsia, low dose aspirin has been demonstrated to be of benefit in specific subgroups. For preterm birth, although there are efficacious treatments, first trimester serum markers or cervical length measurements do not add significantly beyond historical or demographic factors, in prediction of preterm birth. Given the current evidence, first trimester screening, via serum or ultrasound markers, does not have sufficiently high enough positive predictive values for the development of preeclampsia, fetal growth restriction, preterm birth or stillbirth. In order to develop effective screening algorithms for adverse pregnancy outcomes in the first trimester, understanding the heterogeneous phenotype of these complications and the underlying pathophysiology is needed.

Prediction of preeclampsia utilizing the first trimester screening examination

To derive a prediction rule for preeclampsia and early onset preeclampsia requiring delivery <34 weeks using first trimester maternal, ultrasound, and serum markers. Prospective cohort study of women enrolled at first trimester screening. Maternal history, demographics, anthropometry, ultrasound parameters, and serum analytes were compared between women with preeclampsia and normal outcome. The prediction rule was derived by Lasso logistic regression analysis. In 2441 women, 108 (4.4%) women developed preeclampsia, and 18 (0.7%) early preeclampsia. Nulliparity, prior hypertension, diabetes, prior preeclampsia, mean arterial pressure, and the log pregnancy-associate pregnancy protein-A multiples of the median were primary risk factors. Prediction rules for preeclampsia/early preeclampsia had an area under the curve of 0.82/0.83 respectively. Preeclampsia was predicted with 49% sensitivity and early preeclampsia with 55% sensitivity for a 10% false positive rate. First trimester prediction rules using parameters currently available at first trimester screening identify a significant proportion of women with subsequent preeclampsia.

First trimester maternal lipid levels and serum markers of small- and large-for-gestational age infants

Objective: To investigate if first trimester lipids, sonographic parameters and serum markers are related to small- and large-for-gestational age (SGA, LGA) infants.Methods: This study was conducted at Baskent University Adana Research Center between December 2009 and July 2011 and enrolled 433 women. Blood samples were drawn to measure fasting blood glucose, serum triglycerides, cholesterol, very low-density lipoprotein, low-density lipoprotein, high-density lipoprotein, fβ-hCG and pregnancy associated protein-A (PAPP-A) at the first trimester. Crown rump length and nuchal translucency were measured as suggested by the fetal medicine foundation.Results: LGA group was significantly taller (p = 0.016) and SGA group had significantly greater BMI (0.025). SGA fetuses were born at a significantly earlier gestational age (p = 0.001). Univariate analysis revealed that LGA group had significantly lower cholesterol (p = 0.038) and LDL levels (p = 0.041). PAPP-A was significantly lower in SGA Group compared with LGA Group (0.027). After controlling for age, parity, height, pre-pregnant BMI, weight gain during pregnancy and fasting blood sugar, none of the lipids, serum markers or sonographic parameters was related to LGA. PAPP-A was the only parameter significantly associated with SGA after multivariate analysis (p = 0.008).Conclusion: PAPP-A was significantly associated with SGA after controlling for confounders.

The associations of nuchal translucency and fetal abnormalities; significance and implications.

This review of literature describes the first-trimester nuchal translucency (NT) which forms the basis of new form of screening which can lead to a significant improvement in detection of congenital anomalies as compared to second trimester screening programs, the so called genetic-sonogram. A growing body of evidence-based studies has demonstrated that fetal NT can be a powerful prenatal screening tool and combined with first trimester serum markers, it can be incredibly promising in near future. It should be expressed as Multiple of median (MoM) and maintained and monitored like any laboratory analyte. The aim of this review was to investigate the different hypotheses on the aetiology of increased NT. Using a computerized database (PubMed), articles on the aetiology of first-trimester NT were retrieved. Furthermore, the cited references of the retrieved articles were used to find additional articles. Based on ultrasonography, the associations of increased NT fetuses are described in relation with Down syndrome, Cardiac anomalies, and a diverse range of other anomalies. The review concludes that first trimester NT ultrasound has the potential to be used as an important tool for the detection of various congenital abnormalities and an early management can be implemented to reduce the mental trauma of expecting mothers by proper counseling and early diagnosis. For the precise measurements, it should be implemented in a meticulous and coherent manner.

Second trimester serum tests for Down's Syndrome screening.

Down's syndrome occurs when a person has three copies of chromosome 21 - or the specific area of chromosome 21 implicated in causing Down's syndrome - rather than two. It is the commonest congenital cause of mental retardation. Noninvasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing. To estimate and compare the accuracy of second trimester serum markers for the detection of Down's syndrome. We carried out a sensitive and comprehensive literature search of MEDLINE (1980 to May 2007), EMBASE (1980 to 18 May 2007), BIOSIS via EDINA (1985 to 18 May 2007), CINAHL via OVID (1982 to 18 May 2007), The Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 2007, Issue 1), MEDION (May 2007), The Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (May 2007), The National Research Register (May 2007), Health Services Research Projects in Progress database (May 2007). We studied reference lists and published review articles. Studies evaluating tests of maternal serum in women at 14-24 weeks of gestation for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection. Data were extracted as test positive/test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity).We performed quality assessment according to QUADAS criteria. We used hierarchical summary ROC meta-analytical methods to analyse test performance and compare test accuracy. Analysis of studies allowing direct comparison between tests was undertaken. We investigated the impact of maternal age on test performance in subgroup analyses. Fifty-nine studies involving 341,261 pregnancies (including 1,994 with Down's syndrome) were included. Studies were generally high quality, although differential verification was common with invasive testing of only high-risk pregnancies. Seventeen studies made direct comparisons between tests. Fifty-four test combinations were evaluated formed from combinations of 12 different tests and maternal age; alpha-fetoprotein (AFP), unconjugated oestriol (uE3), total human chorionic gonadotrophin (hCG), free beta human chorionic gonadotrophin (βhCG), free alpha human chorionic gonadotrophin (αhCG), Inhibin A, SP2, CA125, troponin, pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PGF) and proform of eosinophil major basic protein(ProMBP).Meta-analysis of 12 best performing or frequently evaluated test combinations showed double and triple tests (involving AFP, uE3, total hCG, free βhCG) significantly outperform individual markers, detecting six to seven out of every 10 Down's syndrome pregnancies at a 5% false positive rate. Tests additionally involving inhibin performed best (eight out of every 10 Down's syndrome pregnancies) but were not shown to be significantly better than standard triple tests in direct comparisons. Significantly lower sensitivity occurred in women over the age of 35 years. Women who miscarried in the over 35 group were more likely to have been offered an invasive test to verify a negative screening results, whereas those under 35 were usually not offered invasive testing for a negative screening result. Pregnancy loss in women under 35 therefore leads to under ascertainment of screening results, potentially missing a proportion of affected pregnancies and affecting the accuracy of the sensitivity. Tests involving two or more markers in combination with maternal age are significantly more sensitive than those involving one marker. The value of combining four or more tests or including inhibin have not been proven to show statistically significant improvement. Further study is required to investigate reduced test performance in women aged over 35 and the impact of differential pregnancy loss on study findings.