Evaluation of Maternal Serum sHLA-G Levels for Trisomy 18 Fetuses Screening at Second Trimester

Human leukocyte antigen-G (HLA-G) has been widely acknowledged to play critical roles in fetal-maternal maintenance. However, the significance of using maternal serum sHLA-G to detect prenatal chromosomal abnormality has not been investigated. In China, prenatal screening using maternal α-fetoprotein (AFP), unconjugated estriol (uE3), and free β subunit human chorionic gonadotropin (β-hCG) in the second trimester has been widely applied. In this study, we evaluated the use of sHLA-G as a screening marker, compared with traditional second trimester prenatal screening. Serum samples from 1,019 singleton women in their second trimester were assessed. Among them, 139 infants were confirmed with trisomy 21 (T21) by karyotyping, 83 were confirmed with trisomy 18 (T18), and the remaining 797 infants had no abnormalities. The sHLA-G levels in maternal sera were significantly lower in pregnant women with T18 fetuses (median: 47.8 U/ml, range: 9.8–234.2 U/ml) and significantly higher in those with T21 fetuses (median: 125.7 U/ml, range: 28.7–831.7 U/ml), compared with the normal controls (median: 106.3 U/ml, range: 50.5–1136.4 U/ml) (p < 0.001). The risk values of the screening of T21 or T18 fetuses were assessed using mean and standard deviation log10 analyte multiples of median (MoM) which showed that the predictive values of sHLA-G were the same as free β-hCG, and superior to AFP and uE3 for T18 screening. Logistic regression analysis revealed that sHLA-G MoM was the highest risk factor associated with pregnant women carrying T18 fetuses [Exp(B): 171.26, 95% CI: 36.30–807.97, p < 0.001]. Receiver operating characteristic (ROC) analysis revealed that the area under ROC curve for sHLA-G MoM was 0.915 (95% CI, 0.871–0.959, p < 0.001), for AFP MoM was 0.796 (95% CI, 0.730–0.861, p < 0.001), for free β-hCG MoM was 0.881 (95% CI, 0.829–0.934, p < 0.001), and for uE3 MoM was 0.876 (95% CI, 0.828–0.923, p < 0.001) in the T18 group. sHLA-G MoM demonstrated the best sensitivity and negative predictive value. For the first time, our findings reveal that sHLA-G is a better second trimester screening marker for the detection of T18 fetuses and the combined application of sHLA-G with AFP, free β-hCG, and uE3 could improve clinical screening for T18 fetuses.

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The Effect of Down Syndrome Biochemical Markers on Predicting Severity of Preeclampsia

10.21203/rs.3.rs-132123/v1 ◽

2020 ◽

Author(s):

AYSE OZBAN

Keyword(s):

Down Syndrome ◽

Pregnant Women ◽

Biochemical Markers ◽

First Trimester ◽

Maternal Serum ◽

Screening Tests ◽

Second Trimester ◽

Study Results ◽

Second Trimester Screening ◽

Trimester Screening

Abstract Objective: This study aims to determine whether it is possible to predict preeclampsia by comparing postpartum results and test results of the pregnant women diagnosed with preeclampsia, whose first and/or second trimester screening tests were accessible, and to demonstrate the predictability of severity and week of onset.Background: 204 patients underwent renal transplantation in our center and 84 of them were female. Five of our patients (one of them had two births) gave birth to a total of 6 pregnancies.Method: 135 patients were diagnosed with preeclampsia and their first and/or second trimester screening tests were accessible, and 366 control participants gave birth to a healthy baby between 37-41 weeks after standard follow-up period for pregnancy and their screening tests were also accessible.Results: The study results show that the first trimester maternal serum PAPP-A level is significantly low in preeclamptic pregnant women, and that the second trimester maternal serum AFP and hCG levels are significantly high and uE3 levels are significantly low The results also suggest that the first and second trimester Down syndrome biochemical markers can be used in preeclampsia screening.Conclusion: Among these markers, uE3 is the parameter which affects the possibility of preeclampsia the most. However, the first and second trimester Down syndrome biochemical markers are not effective in predicting the severity and onset week of preeclampsia.

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Maternal Serum Invasive Trophoblast Antigen (Hyperglycosylated hCG) as a Screening Marker for Down Syndrome during the Second Trimester

Clinical Chemistry ◽

10.1373/clinchem.2004.038059 ◽

2004 ◽

Vol 50 (10) ◽

pp. 1804-1808 ◽

Cited By ~ 20

Author(s):

Glenn E Palomaki ◽

Louis M Neveux ◽

George J Knight ◽

James E Haddow ◽

Raj Pandian

Keyword(s):

United States ◽

Down Syndrome ◽

False Positive Rate ◽

The United States ◽

Maternal Serum ◽

Second Trimester ◽

Marker Panel ◽

Screening Performance ◽

Β Hcg ◽

Screening Marker

Abstract Background: Approximately two million pregnancies in the United States are screened for Down syndrome annually by use of second-trimester maternal serum markers. At present, a combination of four markers can identify 75% of affected pregnancies when 5% of screened women are classified as candidates for amniocentesis. Although not currently included in screening panels, invasive trophoblast antigen (ITA) is a promising screening marker in serum or urine in both the second and first trimesters. This study aims at better defining the screening performance of serum ITA in the second trimester. Methods: In an earlier study, serum samples from an unbiased sampling of 45 Down syndrome (cases) and 238 unaffected (control) pregnancies between 14 and 20 weeks of gestation were collected from various centers in the United States. Samples were aliquoted and stored at −20 °C for 8 years. We measured ITA in these samples and determined the screening performance both univariately and in combination with other screening markers. Results: The median ITA in Down syndrome pregnancies was >3.00 multiples of the median, higher than that found for human chorionic gonadotropin (hCG) or free β-hCG. At a 5% false-positive rate, ITA univariately detected 38% and 40% of Down syndrome pregnancies, respectively, when assigned by date of last menstrual period or ultrasound date. Modeling yielded rates of 45% and 48%. ITA correlated strongly with hCG and free β-hCG. When substituted for either of these in a multiple marker panel, ITA performed comparably. Conclusions: This study indicates that serum ITA is an effective marker for Down syndrome. It is highly correlated with both hCG and free β-hCG and could replace either of them in a multiple marker panel.

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Noninvasive Prenatal Screening Based on Second-Trimester Ultrasonographic Soft Markers in Low-Risk Pregnant Women

Frontiers in Genetics ◽

10.3389/fgene.2021.793894 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yunyun Liu ◽

Xiaosha Jing ◽

Lingling Xing ◽

Sha Liu ◽

Jianlong Liu ◽

...

Keyword(s):

Pregnant Women ◽

Prenatal Screening ◽

Sex Chromosome ◽

Nasal Bone ◽

Low Risk ◽

Trisomy 13 ◽

Second Trimester ◽

Predictive Values ◽

Noninvasive Prenatal Screening ◽

Hypoplastic Nasal Bone

Background: We aimed to assess the clinical application of noninvasive prenatal screening (NIPS) based on second-trimester ultrasonographic soft markers (USMs) in low-risk pregnant women.Methods: Data of pregnant women between April 2015 and December 2019 were retrospectively analyzed. Pregnant women [age at expected date of confinement (EDC) of <35 years; low risks for trisomy 21 (T21) and trisomy 18 (T18) based on maternal serum screening; presenting second-trimester USMs (7 types)] who successfully underwent NIPS and had available follow-up information were included in our study. Cases with positive NIPS results were prenatally diagnosed. All patients were followed up for 6 months to 2 years after NIPS, and their clinical outcomes were obtained. Subgroup analyses were performed according to the different USMs.Results: NIPS suggested that among a total of 10,023 cases, 37 (0.37%) were at high risk of aneuploidy, including 4 T21, 6 trisomy 13 (T13), and 27 sex chromosome abnormalities (SCA). Ten cases with aneuploidy (0.10%) were confirmed by prenatal diagnosis, consisting of two T21 and eight SCA. The eight fetuses with SCA consisted of one monosomy X, two XXY, one XXXY, one XXX, one XYY, and two mosaicisms. T21 was detected in one fetus with absent or hypoplastic nasal bone and one fetus with echogenic intracardiac focus (EICF). SCA was detected in five fetuses with EICF, two fetuses with multiple soft markers, and one fetus with echogenic bowel. The positive rate of chromosomal aneuploidy was significantly higher in fetuses with absent or hypoplastic nasal bone (6.25 vs. 0.10%, p = 0.017), echogenic bowel (3.7 vs. 0.10%, p = 0.029), and multiple soft markers (0.678 vs. 0.10%, p = 0.045) than in the total fetuses. The positive predictive values (PPVs) of NIPS in these three groups were 100%, 50%, and 100%, respectively. EICF accounted for 93.25% (9,346/10,023) of the study population, whereas the PPV of NIPS was only 20%.Conclusion: NIPS is an advanced screening test for low-risk pregnant women. In the 10,023 pregnant women sampled, SCA were more common than autosomal trisomy, and EICF was the most frequent USM but the least predictive aneuploidy. Further aneuploidy evaluation is suggested for low-risk pregnant women whose ultrasound indicates absent or hypoplastic nasal bone, echogenic bowel, or multiple soft markers. NIPS can serve as a second-line complementary screening for these women.

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The relationship between first and second trimester biochemical parameters used to screen down syndrome and intrahepatic cholestasis of pregnancy

Medical Science and Discovery ◽

10.36472/msd.v8i12.630 ◽

2021 ◽

Vol 8 (12) ◽

pp. 692-697

Author(s):

Cuma Taşın ◽

Nezaket Kadıoğlu ◽

Revan Sabri Çiftçi ◽

Hatun Çolak ◽

Hakan Aytan

Keyword(s):

Intrahepatic Cholestasis ◽

First Trimester ◽

Intrahepatic Cholestasis Of Pregnancy ◽

Second Trimester ◽

First Trimester Screening ◽

Predictive Values ◽

Second Trimester Screening ◽

Trimester Screening ◽

Β Hcg ◽

Cholestasis Of Pregnancy

Objective: To assess the role of first and second-trimester screening biomarkers pregnancy-associated plasma protein-A(PAPP-A), free beta-human chorionic gonadotropin(free ß-hCG), estriol, alpha-fetoprotein and total β-hCG in the early diagnosis of intrahepatic cholestasis of pregnancy (ICP). Materials and Methods: Patients with ICP admitted to Mersin University Hospital for delivery between 2015 and 2019 and had first and second-trimester aneuploidy screening tests performed in the same facility were retrospectively assessed. Randomly 60 pregnant women without comorbid conditions during the same period were included as controls. Data regarding demographic characteristics, laboratory values including free ß-hCG and PAPP-A in first-trimester screening and total ß-hCG, estriol and alpha- fetoprotein in second-trimester screening were compared. Results: There were 46 eligible patients with ICP. In first trimester screening, it was found that PAPP-A MoM was significantly lower (0.89±0.55 vs. 1.94±0.73; p=0.035) while free ß-hCG MoM was significantly higher in ICP group when compared to controls (1.84±0.59 vs. 0.99±0.47; p=0.018). In second trimester screening, no significant difference was detected in aneuploidy markers between groups. For prediction of ICP development, first trimester free β-hCG >1.44 MoM was found to have a sensitivity of 50%, a specificity of 80% and positive and negative predictive values of 33% and 88.9% respectively. Similarly first trimester PAPP-A values <1.075 MoM was found to have 80% and 75% sensitivity and specificity with positive and negative predictive values of 75% and 44% respectively. Conclusion: Low PAPP-A MoM value and elevated free ß-hCG in first trimester seem to be associated with ICP development.

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Maternal immune response and air pollution exposure during pregnancy: insights from the Early Markers for Autism (EMA) study

Journal of Neurodevelopmental Disorders ◽

10.1186/s11689-020-09343-0 ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Heather E. Volk ◽

Bo Park ◽

Calliope Hollingue ◽

Karen L. Jones ◽

Paul Ashwood ◽

...

Keyword(s):

Air Pollution ◽

Intellectual Disability ◽

Prenatal Screening ◽

Maternal Serum ◽

Serum Samples ◽

Maternal Immune Activation ◽

Early Markers ◽

Air Pollution Exposure ◽

Pollution Exposure ◽

The Relationship

Abstract Background Perinatal exposure to air pollution and immune system dysregulation are two factors consistently associated with autism spectrum disorders (ASD) and other neurodevelopmental outcomes. However, little is known about how air pollution may influence maternal immune function during pregnancy. Objectives To assess the relationship between mid-gestational circulating levels of maternal cytokines/chemokines and previous month air pollution exposure across neurodevelopmental groups, and to assess whether cytokines/chemokines mediate the relationship between air pollution exposures and risk of ASD and/or intellectual disability (ID) in the Early Markers for Autism (EMA) study. Methods EMA is a population-based, nested case–control study which linked archived maternal serum samples collected during weeks 15–19 of gestation for routine prenatal screening, birth records, and Department of Developmental Services (DDS) records. Children receiving DDS services for ASD without intellectual disability (ASD without ID; n = 199), ASD with ID (ASD with ID; n = 180), ID without ASD (ID; n = 164), and children from the general population (GP; n = 414) with no DDS services were included in this analysis. Serum samples were quantified for 22 cytokines/chemokines using Luminex multiplex analysis technology. Air pollution exposure for the month prior to maternal serum collection was assigned based on the Environmental Protection Agency’s Air Quality System data using the maternal residential address reported during the prenatal screening visit. Results Previous month air pollution exposure and mid-gestational maternal cytokine and chemokine levels were significantly correlated, though weak in magnitude (ranging from − 0.16 to 0.13). Ten pairs of mid-pregnancy immune markers and previous month air pollutants were significantly associated within one of the child neurodevelopmental groups, adjusted for covariates (p < 0.001). Mid-pregnancy air pollution was not associated with any neurodevelopmental outcome. IL-6 remained associated with ASD with ID even after adjusting for air pollution exposure. Conclusion This study suggests that maternal immune activation is associated with risk for neurodevelopmental disorders. Furthermore, that prenatal air pollution exposure is associated with small, but perhaps biologically relevant, effects on maternal immune system function during pregnancy. Additional studies are needed to better evaluate how prenatal exposure to air pollution affects the trajectory of maternal immune activation during pregnancy, if windows of heightened susceptibility can be identified, and how these factors influence neurodevelopment of the offspring.

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Second-trimester maternal serum progesterone levels in Turner syndrome with and without hydrops and in trisomy 18

Prenatal Diagnosis ◽

10.1002/(sici)1097-0223(199905)19:5<476::aid-pd548>3.0.co;2-b ◽

1999 ◽

Vol 19 (5) ◽

pp. 476-479 ◽

Cited By ~ 12

Author(s):

G. M. Lambert-Messerlian ◽

D. N. Saller ◽

M. B. Tumber ◽

C. A. French ◽

C. J. Peterson ◽

...

Keyword(s):

Turner Syndrome ◽

Maternal Serum ◽

Trisomy 18 ◽

Second Trimester ◽

Serum Progesterone

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Serum Concentrations of Selected Organochlorines in Pregnant Women and Associations with Pregnancy Outcomes. A Cross-Sectional Study from Two Rural Settings in Cambodia

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17207652 ◽

2020 ◽

Vol 17 (20) ◽

pp. 7652

Author(s):

Margit Steinholt ◽

Shanshan Xu ◽

Sam Ol Ha ◽

Duong Trong Phi ◽

Maria Lisa Odland ◽

...

Keyword(s):

Polychlorinated Biphenyls ◽

Pregnant Women ◽

Gestational Age ◽

Low Income ◽

Cross Sectional Study ◽

Maternal Serum ◽

Sectional Study ◽

Serum Samples ◽

Cross Sectional ◽

Rural Settings

We conducted a cross-sectional study among 194 pregnant women from two low-income settings in Cambodia. The inclusion period lasted from October 2015 through December 2017. Maternal serum samples were analyzed for persistent organic pollutants (POPs). The aim was to study potential effects on birth outcomes. We found low levels of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCP), except for heptachlors, β-hexachlorocyclohexane (HCH), heptachlor epoxide, and p,p’-DDE. There were few differences between the two study locations. However, the women from the poorest areas had significantly higher concentrations of p,p’-DDE (p < 0.001) and hexachlorobenzene (HCB) (p = 0.002). The maternal factors associated with exposure were parity, age, residential area, and educational level. Despite low maternal levels of polychlorinated biphenyls, we found significant negative associations between the PCB congeners 99 (95% CI: −2.51 to −0.07), 138 (95% CI: −1.28 to −0.32), and 153 (95% CI: −1.06 to −0.05) and gestational age. Further, there were significant negative associations between gestational age, birth length, and maternal levels of o,p’-DDE. Moreover, o,p’-DDD had positive associations with birth weight, and both p,p’-DDD and o,p’-DDE were positively associated with the baby’s ponderal index. The poorest population had higher exposure and less favorable outcomes.

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Relation between maternal weight and serum alpha-fetoprotein concentration during the second trimester.

Clinical Chemistry ◽

10.1093/clinchem/27.1.133 ◽

1981 ◽

Vol 27 (1) ◽

pp. 133-134 ◽

Cited By ~ 43

Author(s):

J E Haddow ◽

E M Kloza ◽

G J Knight ◽

D E Smith

Keyword(s):

Body Weight ◽

Pregnant Women ◽

Reference Interval ◽

Maternal Serum ◽

Alpha Fetoprotein ◽

Second Trimester ◽

Maternal Weight ◽

Diagnostic Aid ◽

Serum Alpha Fetoprotein ◽

Clinical Interest

Abstract Maternal serum alpha-fetoprotein concentrations are influenced by maternal weight during the second trimester. Heavier pregnant women have lower median values, apparently as a result of a diluting effect of larger blood volume. This phenomenon is of clinical interest because alpha-fetoprotein concentration in a pregnant woman's serum is one of the factors considered in assessing risk of poor outcome. A revision of the reference interval for alpha-fetoprotein to take body weight into account might improve its use as a diagnostic aid, especially in heavier women.

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