Very elevated hCGß (≥10 multiple of the median) in maternal marker screening for Down syndrome: Frequency, etiologies, outcomes, and guidelines.

AIM: This aim of this study was to detail maternal and fetal anomalies observed on a national scale in a large French cohort of patients presenting high hCG values (≥10 multiple of the median [MoM]) at Down syndrome screening in order to define clear and optimal guidelines. METHODS: This is a retrospective multicenter study based on a French annual database of all trisomy 21 screenings. Our study targeted and studied cases with hCG or hCGß values ≥10 MoM. Complementary exams and outcomes were analyzed. RESULTS: The calculated frequency was 0.05% for hCGß ≥10 MoM in unselected patients. For this series of 289 cases, a complication of the pregnancy or a poor outcome was observed in 145 cases (51%) as follows: 96 (66%) cases of fetal disease, 23 (16%) of maternal disease, 5 (3.5%) of placental anomalies and 21 (14.5%) of systemic disease concerning mother, fetus and placenta. CONCLUSION: This study establishes the frequency of hCG or hCGß values ≥10 MoM, presents a flow chart that optimizes follow-up, and gives clear information for patients presenting with such abnormal values at trisomy 21 screening.

Ophthalmic artery Doppler in combination with other biomarkers in prediction of pre-eclampsia at 35-37 weeks' gestation.

OBJECTIVE: To examine the potential value of maternal ophthalmic artery Doppler at 35-37 weeks' gestation in combination with the established biomarkers of pre-eclampsia (PE), including mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1), in the prediction of subsequent development of PE. METHODS: This was a prospective observational study in women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination for fetal anatomy and growth, assessment of flow velocity waveforms from the maternal ophthalmic arteries, and measurement of MAP, UtA-PI, serum PlGF and serum sFlt-1. The competing-risks model was used to estimate the individual patient-specific risks of delivery with PE at any time and at < 3 weeks after assessment by a combination of maternal demographic characteristics and medical history with biomarkers. The area under the receiver-operating-characteristics curve and detection rate (DR) of delivery with PE, at a 10% false-positive rate (FPR), in screening by combinations of maternal factors with ophthalmic artery second to first peak of systolic velocity ratio (PSV ratio), MAP, UtA-PI, serum PlGF and serum sFlt-1 were determined. The modeled performance of screening for PE was also estimated. RESULTS: The study population of 2287 pregnancies contained 60 (2.6%) that developed PE, including 19 (0.8%) that delivered with PE at < 3 weeks after assessment. The PSV ratio improved the prediction of PE with delivery at any stage after assessment provided by maternal factors alone (from 25.4% to 50.6%), maternal factors and MAP (54.3% to 62.7%), maternal factors, MAP and PlGF (68.3% to 70.8%) and maternal factors, MAP, PlGF and sFlt-1 (75.7% to 76.7%), at a FPR of 10%. The PSV ratio also improved the prediction of PE with delivery at < 3 weeks after assessment provided by maternal factors alone (from 31.0% to 69.4%), maternal factors and MAP (74.1% to 83.4%), maternal factors, MAP and UtA-PI (77.1% to 85.0%) and maternal factors, MAP and PlGF (84.8% to 88.6%). The empirical results for DR at a 10% FPR were consistent with the modeled results. Screening by a combination of maternal factors with MAP and PSV ratio also detected 59.4% (95% CI, 58.6-82.5%) of cases of gestational hypertension with delivery at any stage after assessment, and 86.7% (95% CI, 82.4-100%) of those with delivery at < 3 weeks after assessment. CONCLUSION: Ophthalmic artery Doppler could potentially improve the performance of screening for PE at 35-37 weeks, especially imminent PE with delivery within 3 weeks after assessment, but further studies are needed to validate this finding. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Relations between second-trimester aneuploidy screening results and prediction of labour induction success in term pregnancies.

We aimed to assess whether the second-trimester maternal serum markers could be used for the prediction of labour induction success. This prospective study enrolled women planned labour induction at term. Women were assigned to one of two groups: vaginal prostaglandin or balloon dilatation. All patients were evaluated for Bishop score, maternal serum oestriol, human chorionic gonadotropin and progesterone at the time of second-aneuploidy screening. The total successful rate for induction of labour was 63.9% in both groups. Maternal serum oestriol multiple of median (MoM) values were significantly lower among the caesarean section group compared to the vaginal delivery group (p < .001). A MoM value of 0.74 for oestriol was associated with a sensitivity of 75.9%, specificity of 41.0%, a positive predictive value of 76.6% and a negative predictive value of 58.0% for a successful induction of labour. Oestriol had a good performance in the prediction of successful induction of labour at term.IMPACT STATEMENTWhat is already known on this subject? Induction of labour is a common procedure undertaken whenever the benefits of prompt delivery outweigh the risks of expectant management. Previous studies have reported that a decreased progesterone/oestradiol ratio and increased maternal plasma oestriol levels are associated with successful labour. What the results of this study add? The results of this study showed that second-trimester oestriol multiple of median (MoM) value provide a significant contribution to the efforts of the prediction of successful induction of labour in term pregnancy, having a sensitivity of 69.8%, specificity of 92.4%, positive predictive value of 83.3% and negative predictive value of 82.5%.What the implications are of these findings for clinical practice and/or further research? This finding can be used as an additional method for prediction of labour induction as well as multiparity and Bishop score. This adds new valuable data to the literature which could be used for systematic reviews and for implementing guidelines and protocols on labour induction.

Maternal serum endothelial cell-specific molecule-1 level and its correlation with severity of early-onset preeclampsia.

Preeclampsia (PE), the primary pathology of which is endothelial cell (EC) dysfunction, has long-lasting effects such as cardiovascular disease. Therefore, it was decided to investigate the maternal serum concentrations of EC-specific molecule-1 in patients with early-onset preeclampsia (E-PE). This study was conducted on 33 pregnant women with E-PE and 35 healthy pregnant women matched for gestational age. EC-specific molecule-1 level was measured using a commercially available enzyme-linked immunosorbent assay kit. The mean EC-specific molecule-1 concentrations were not significantly different between the groups (651.7 ± 632.2 pg/mL vs. 425.9 ± 263.0 pg/mL, p=.056). Among women with E-PE, the median EC-specific molecule-1 concentration did not differ significantly by disease severity (p=.115). EC-specific molecule-1 is not involved in the pathogenesis of E-PE. However, some studies in the literature report that EC-specific molecule-1 concentrations increased during the diagnosis of PE. Therefore, well-designed studies with a large sample are needed in cases of E-PE.Impact StatementWhat is already known on this subject? There is an increased risk of cardiovascular disease (CVD) in early-onset preeclampsia (E-PE) which is linked with endothelial dysfunction. Endothelial cell (EC)-specific molecule-1 stands out as an important marker in EC dysfunction related conditions such as preeclampsia.What the results of this study add? This study showed that EC-specific molecule-1 is not associated with the CVDs risk linked with endothelial dysfunction in E-PE. Additionally, there was also no significant relationship was detected between the severity of E-PE and EC-specific molecule-1 concentrations.What the implications are of these findings for clinical practice and/or further research? Endothelial cell-specific molecule-1 is not involved in the pathogenesis of E-PE. Moreover, advantageous and easy-to-measure markers are needed in larger sample studies to better understand the aetiology of E-PE.

Effect of anti-epileptic drugs on first trimester screening test results.

OBJECTIVE: To evaluate first trimester screening test parameters in epileptic patients using anti-epileptic drugs. MATERIALS AND METHODS: We retrospectively evaluated first trimester screening test results of 23 epileptic pregnant women using anti-epileptic drugs with a control group consisting of 92 healthy pregnancies. The anti-epileptic drugs used in this study were carbamazepine, levatiracetam, valproic acid and lamotrigine. Single drug or multi-drug regimens were used according to the clinical conditions. Patients with any known chronic or acute disease and drug usage were excluded from the study. Comparisons were performed via Mann-Whitney U test. RESULTS: First trimester screening test biochemical markers were compared and maternal serum PAPP-A MoM values were found to be similar in study and control groups while ß-hCG MoM values were significantly higher in pregnancies using epileptic drugs (p: 0,737 and p < 0.001, respectively). CONCLUSION: Biochemical first trimester screening test results may be affected by anti-epileptic drug usage, which may lead to misinterpretation of the risk level. Thus, validation of MoM values should be necessary in order to obtain optimal results.

Diagnostic accuracy of sFlt1/PlGF ratio as a marker for preeclampsia.

BACKGROUND: Preeclampsia (PE) is a serious complication of pregnancy and one of the main causes of maternal and neonatal mortality and morbidity in the world. Finding a biomarker with high sensitivity and specificity could lead to prediction and early diagnosis of the disease and reduces its complications. In this study, we evaluated diagnostic accuracy of Soluble fms-like tyrosine kinase-1 (sFlt-1) to Placental growth factor (PlGF) ratio for diagnosis of PE. METHODS: The cases included 23 mild, 15 severe preeclamptic patients, and 20 normal term pregnant women as control referred to GYN ward of the Persian Gulf Hospital in Bandar Abbas from 2014 to 2016. Levels of sFlt-1 and PlGF were measured. Receiver Operating Characteristic (ROC) curve analysis was applied to calculate diagnostic accuracy of sFlt-1/PlGF ratio. RESULTS: The mean Level of sFlt-1/PlGF in PE patients (91.33 ng/ml) was significantly higher than control women (17.62) (P<0.001). ROC curve analysis showed sFlt-1/PlGF ratio diagnostic accuracy in preeclamptic patients with Area Under Curve (AUC) of 0.90, the best cut-off value of 24.96, sensitivity and specificity of 84.2 and 85.0%, respectively. CONCLUSIONS: Our data showed sFlt-1/PlGF ratio has higher accuracy for differentiating PE patients from non-PEs in comparison with its power for differentiating severe or early onset forms of the disease.

Association between the fetal cerebroplacental ratio and biomarkers of hypoxia and angiogenesis in the maternal circulation at term.

OBJECTIVES: A low fetal cerebroplacental ratio (CPR) in late pregnancy is a marker of a fetus that has failed to reach its growth potential and is associated with a variety of perinatal and pregnancy complications. It is not known if it is also correlated with aberrations in angiogenic, hypoxia-responsive or inflammatory cytokine levels in the maternal circulation. We investigated if there were any differences in levels of biomarkers of angiogenesis, endothelial cell dysfunction, hypoxia and/or inflammation in term pregnancies with a low fetal CPR compared to controls. We hypothesized that as the CPR is a marker of suboptimal growth, this would be reflected in a shift towards upregulation of hypoxia-responsive factors even in non-small for gestational age fetuses. STUDY DESIGN: We used Multiplex ELISA to measure a panel of 28 candidate biomarkers of angiogenesis and/or hypoxia in pre-labour maternal plasma from 113 women at term, stratified for CPR <10th centile vs. CPR >10th centile. Plasma levels of the biomarkers were measured using 2 multiplex Luminex assays - a commercially available human angiogenesis/growth factor panel (R&D Systems®), comprising 15 analytes and an in-house custom panel of a further 13 candidate biomarkers. RESULTS: Of the 28 candidate biomarkers investigated, we found significantly elevated levels of Carbonic Anhydrase 9 and soluble Fms-like tyrosine kinase (Vascular Endothelial Growth Factor Receptor 1), and lower levels of Placental Growth Factor in plasma from women with a low fetal CPR. The soluble Fms-like tyrosine kinase-1/Placental Growth Factor ratio was also markedly elevated in this cohort. We also demonstrated significant inverse correlations between the fetal CPR and Carbonic Anydrase 9, soluble Fms-like tyrosine kinase and Hepatocyte Growth Factor. CONCLUSIONS: A low fetal CPR is associated with changes in some hypoxia-responsive and angiogenesis factors in the maternal circulation in pregnancies with normally grown fetuses.

Copeptin and mid-regional pro-atrial natriuretic peptide in women with suspected or confirmed pre-eclampsia: comparison with sFlt-1/PlGF ratio.

OBJECTIVES: Arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) may contribute to the pathogenesis of pre-eclampsia (PE), but their role remains to be elucidated. Our aims were to evaluate the surrogates of AVP and ANP, C-terminal pro-AVP (copeptin) and mid-regional pro-ANP (MR-proANP), as biomarkers for the prediction of PE-related pregnancy complications and whether they are associated with angiogenic markers and/or clinical manifestations of PE. METHODS: This was a retrospective analysis of a prospective cohort study that enrolled pregnant women with suspected or confirmed PE, between December 2013 and April 2016. From each patient, a blood sample was obtained at study entry and serum levels of copeptin, MR-proANP, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured. We evaluated the ability of sFlt-1, PlGF, sFlt-1/PlGF ratio, copeptin and MR-proANP, assessed either alone or combined with traditional predictors (gestational age, parity, diastolic blood pressure and proteinuria), to predict maternal complications and fetal/neonatal complications. Models were compared using concordance statistic (C-index). RESULTS: A total of 526 women were evaluated in the study. Women with confirmed PE displayed elevated serum copeptin and MR-proANP levels in comparison to those with suspected PE but no hypertensive disease of pregnancy. When combined with traditional predictors, the sFlt-1/PlGF ratio displayed a higher C-index than copeptin and MR-proANP (0.76, 0.63 and 0.67, respectively, vs 0.60 for the traditional predictors alone) for the prediction of maternal complications. Similarly, for the prediction of fetal/neonatal complications, the sFlt-1/PlGF ratio displayed a higher C-index than copeptin and MR-proANP when added to the traditional model (0.83, 0.79 and 0.80, respectively, vs 0.79 for the traditional predictors alone). When subdividing women according to sFlt-1/PlGF ratio (≥ 85 vs < 85), no differences in copeptin levels were observed, while MR-proANP level was elevated in women with sFlt-1/PlGF ratio ≥ 85. Multiple regression analysis revealed that copeptin and MR-proANP were independent determinants of proteinuria. CONCLUSIONS: Copeptin and MR-proANP have limited value in predicting PE-related complications when compared with the sFlt-1/PlGF ratio. However, both copeptin and MR-proANP were associated with proteinuria, with copeptin exerting this effect independently of the sFlt-1/PlGF ratio. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Ultrasound features prior to 11 weeks' gestation and first-trimester maternal factors in prediction of hypertensive disorders of pregnancy.

OBJECTIVES: Maternal hypertensive disorders (MHD), including pregnancy-induced hypertension and pre-eclampsia, are estimated to occur in 7-10% of pregnancies worldwide and have significant short- and long-term implications for both mother and fetus. This study aimed to determine the association of conventional and novel early first-trimester ultrasound measures with MHD and whether these ultrasound measures, combined with maternal characteristics and biochemistry, improve the prediction of MHD. METHODS: This was a prospective cohort study of consecutive women with a singleton pregnancy, attending for an early (5 + 1 to 11 + 0 weeks' gestation) ultrasound examination at a private obstetric ultrasound practice between February 2016 and August 2018. Recorded ultrasound measurements included mean sac diameter, yolk sac diameter, crown-rump length, fetal heart rate (FHR), trophoblast thickness, trophoblast volume (TV) and mean uterine artery pulsatility index. Maternal biochemistry was assessed at 10-14 weeks and included beta-human chorionic gonadotropin, pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PlGF) and maternal serum alpha-fetoprotein. Regression models were fitted for each ultrasound parameter and multiples of the median (MoM) were calculated. All measures were compared between women who had a normotensive outcome and those who subsequently developed MHD. Logistic regression analysis was used to create a prediction model for MHD based on maternal characteristics, ultrasound measurements at 5 + 1 to 11 + 0 weeks' gestation and maternal biochemistry at 10-14 weeks. RESULTS: In total, 1141 women were included in the analysis, of whom 1086 (95.2%) were normotensive at delivery and 55 (4.8%) developed MHD. Women who developed MHD weighed significantly more than did normotensive women (P < 0.0001). Mean MoM values for TV (P = 0.006), PAPP-A (P = 0.031) and PlGF (P = 0.044) were decreased significantly in pregnancies that subsequently developed MHD. The proposed logistic regression model includes maternal weight and height and MoM values for TV, FHR and PlGF, resulting in an area under the receiver-operating-characteristics curve of 0.80 (95% CI, 0.75-0.86). CONCLUSION: The combination of maternal weight and height, TV and FHR, measured prior to 11 weeks' gestation, and first-trimester PlGF appears to have good predictive value for development of MHD later in pregnancy. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

PAPP-A concentrations change in patients with gestational diabetes.

Our aim was to assess the relationship between gestational diabetes and glucose intolerance regarding maternal serum PAPP-A and free ß-hCG concentrations in first trimester pregnancies. This study was conducted on 278 women between 18-45 years old with singleton pregnancies. The subjects were divided into four groups, according to their 50 and 100 g OGTT results. Group 1 was the Control Group, Group 2 with positive 50 g OGTT results, but negative 100 g, Group 3 had gestational diabetes after testing with 50 g OGTT (≥180 mg/dl) or with 100 g OGTT. Finally Group 4 was made of women with a one single high glucose level after testing with 100 g OGTT. These groups were analysed in terms of OGTT results. In the GDM group, serum PAPP-A concentrations were significantly lower when compared with the Control Group's (p = 0.015). There was either no significant differences regarding free ß-hCG concentrations among the groups. GDM rate is 21.1%, the patients with GDM had significantly low concentrations of serum PAPP-A but their f ß-hCG concentrations did not change. Our results are supported by several studies. However, we need greater numbered studies for exact results.IMPACT STATEMENTWhat is already known on this subject? Pregnancy associated plasma protein A (PAPP-A) is produced by the placenta in pregnancy. PAPP-A cleaves insulin-like growth factor (IGF) binding proteins. It would appear to have a role in regulating IGF bioavailability in pregnancy. This is important as the IGF axis plays a critical role in fetal growth, and placental growth and function during pregnancy. Some studies have reported that PAPP-A levels were impaired among women who subsequently developed GDM.What do the results of this study add? The patients with GDM had significantly low concentrations of serum PAPP-A but their free ß-hCG levels did not change.What are the implications of these findings for clinical practice and/or further research? By looking at PAPP-A concentrations, we can predict patients that will be gestational diabetic and take precautions to protect the babies health, such as their diet or exercise.

Assessment of ß-human-derived chorionic gonadotrophic hormone (ßhCG) and pregnancy-associated plasma protein A (PAPP-A) levels as predictive factors of preeclampsia in the first trimester among Iranian women: a cohort study.

BACKGROUND: Preeclampsia (PE) is a leading cause of maternal and perinatal mortality. There are controversial findings regarding the prediction of PE through the assessment of the Pregnancy-Associated Plasma Protein A (PAPP-A) and ß-Human-Derived Chorionic Gonadotrophic hormone (ßhCG) levels in the first trimester of pregnancy. Therefore, this cohort study was conducted to evaluate of PAPP-A and ßhCG levels as predictive factors for PE development in the first trimester among Iranian women. METHODS: In this cohort study, a total of 4605 volunteer Primigravida and Multigravida women were selected by the census from 16 randomly selected Health Centers in Isfahan, Iran, from July 2016 to June 2018. Eligible pregnant women participated in the study had already undergone fetal anomalies screening tests between 11 + 0 and 13 + 6 weeks of pregnancy and their PAPP-A and ßhCG biomarkers were adjusted to the Multiples of the Median (MOM). MOM PAPP-A <  0.4 and MOM ßhCG > 3 were considered abnormal. The samples were followed up until delivery. The biomarkers' levels were compared in the two groups of women with and without PE and Relative risk (RR) and odds ratio (OR) of PE calculated. RESULTS: In the PE group, the mean MOM PAPP-A was significantly lower (1 vs. 1.09 with P = 0.006) and MOM ßhCG was significantly higher (1.51 vs. 1.14 with P = 0.001) than the group without PE. RR and OR for PE in subjects with MOM PAPP-A <  0.4 were reported as follows: RR = 2.49, (p = 0.001) and OR = 2.09, (p = 0.001). RR and OR for PE in subjects with MOM ßhCG > 3 were also reported as follows: RR = 4.02, (p = 0.001) and OR = 5.65, (p = 0.001). Adjusted OR for MOM PAPP-A <  0.4 and MOM ßhCG > 3 was obtained as follows: OR = 2.09 (P = 0.001) and OR = 5.65 (P = 0.001), respectively. CONCLUSION: The results of the study showed that the high levels of ßhCG would cause 5.65 times increase and the low levels of PAPP-A would cause 2.09 times increase in the chance of developing PE.

Establishment of reference intervals for maternal blood and umbilical cord blood procalcitonin in healthy Chinese women in late pregnancy.

AIM: To establish reference intervals (RIs) for maternal blood and umbilical cord blood procalcitonin (PCT) in healthy Chinese women in late pregnancy. METHODS: One hundred and twenty-seven healthy Chinese women in late pregnancy, including 70 vaginal deliveries and 57 cesarean section deliveries, were retrospectively analyzed. These pregnant women gave birth to 58 male infants and 69 female infants. Another 127 age-matched healthy women who were not pregnant were enrolled as the control group. PCT levels in maternal blood, umbilical cord blood and control blood were determined using electrochemiluminescence immunoassay. The RIs of PCT were defined using an intermediate 95% interval. RESULTS: The RIs for maternal blood and umbilical cord blood PCT were 0.020-0.075 ng/mL and 0.020-0.159 ng/mL, respectively. The cord blood PCT level was not significantly different between different delivery methods (P > 0.05). In contrast, the umbilical cord blood PCT in female newborns was higher than that in male newborns (0.088 ± 0.046 ng/mL vs 0.072 ± 0.030 ng/mL, P < 0.05). CONCLUSION: Maternal blood and umbilical cord blood PCT of Chinese women in late pregnancy have different RIs, and umbilical cord blood PCT level is affected by the gender of newborns.

Hypertensive disorders of pregnancy are associated with an inflammatory state: evidence from hematological findings and cytokine levels.

BACKGROUND: Abnormalities of blood cell counts and of cytokine profiles in women with hypertensive disorders of pregnancy (HDP) have been reported in several studies. Although their cause-effect relationships to HDP are not yet clear, detecting and monitoring these alterations can be of use for prognosis and management of HDP. This study aimed to determine hematological, coagulation and cytokine profiles in hypertensive as compared to normotensive pregnancy and to identify correlations between these profiles. METHODS: This was a hospital-based comparative cross-sectional study conducted from September 2017 to February 2018. There were two groups: the comparison group consisted of 77 normotensive pregnant women attending the antenatal clinic of Muhimbili National Hospital (MNH); the index group consisted of 76 hypertensive pregnant women admitted to the maternity block of the same hospital. Hematological and cytokine parameters were compared between the hypertensive and the normotensive group. We analyzed the data using Student's independent t-test when the data were normally distributed; and the Mann-Whitney U-test when the data were not normally distributed. Kruskal Wallis with Dunn's multiple comparison tests was run for subgroup analysis and correlation studies were done using Spearman ranking. RESULTS: Hemoglobin levels were slightly but significantly lower, (P < 0.01) in women with HDP compared to normotensive (N) women; the same was true for platelet counts (P < 0.001). The red cell distribution width (RDW) was slightly but significantly higher in HDP than in N. Neutrophil counts and Interleukin 6 (IL-6) levels were significantly (P < 0.001) higher in HDP than in N; and within HDP IL-6 levels increased with increasing severity of HDP. A novel remarkable finding was that eosinophil counts, normal in N, were lower and lower with increasing severity of HDP, to the point that they were nearly absent in women with eclampsia. CONCLUSION: There are significant changes in hematological, cytokine and coagulation parameters in pregnant women with hypertensive disorders compared to normotensive pregnant women. The picture that emerges is that of an inflammatory state associated with hypertensive disorders of pregnancy.

Second Trimester Serum Biomarker Screen for Fetal Aneuploidies as a Predictor of Preterm Delivery: A Population-Based Study.

OBJECTIVE: To determine the association between second-trimester serum Down syndrome screening (alpha-fetoprotein [AFP] free beta-human chorionic gonadotropin [b-hCG] unconjugated estriol [uE3]) and preterm birth and to create predictive models for preterm birth. METHODS: Secondary analysis on a prospective database of pregnancies undergoing second-trimester screen with complete follow-up. The multiples of medians (MoM) of the biomarkers were compared between the group of term, preterm (< 37 weeks), early preterm (< 34 weeks), and very early preterm (< 32 weeks) delivery. Predictive models were developed based on adjusted MoMs and logistic regression and diagnostic performances in predicting preterm birth were determined. RESULTS: Of 20,780 pregnancies, 1,554 (7.5), 363 (1.7), and 158 (0.8%) had preterm, early preterm, and very early preterm birth respectively. High levels of AFP and b-hCG but low levels of uE3 were significantly associated with higher rates of preterm, early preterm and very early preterm delivery. The predictive models had diagnostic performance in predicting preterm birth with the areas under the ROC curve of 0.688, 0.534, 0.599, and 0.718 for AFP, b-hCG, uE3, and combined biomarkers respectively. CONCLUSION: The second trimester Down syndrome screening could also be used as a tool of risk identification of preterm birth in the same test, without extra-effort and extra-cost.

Seroprevalence of hepatitis B, hepatitis C, and HIV in pregnant women from Eastern Turkey.

BACKGROUND/AIMS: The vertical transmission of hepatitis B virus, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections are essential public health problems. In this study, we aimed to investigate the seroprevalence of the aforementioned infections among pregnant women. MATERIALS AND METHODS: This study was done retrospectively on pregnant women who presented for antenatal follow-up and delivery between 2013 and 2016. Data were collected from the hospital's electronic health records and patient files. Blood samples were analyzed at the microbiology laboratory of the hospital. HBsAg, anti-HBs, anti-HCV, and anti-HIV titers were tested using the chemiluminescence enzyme immunoassay method (Architect, Abbott Laboratories, USA). RESULTS: HBsAg and anti-HBs levels were tested in 35,295 pregnant women aged 18-45 years. The HBsAg and anti-HBs levels were positive in 425 (1.2%) and 9583 (27.7%) patients, respectively. From 2013 to 2016, the HBV carrier rates have continuously decreased from 1.4% to 0.8%, whereas the anti-HBs positivity has increased from 25.4% to 30.2%. Anti-HCV was detected in 6 of the 9709 (0.06%) patients. All the 7113 pregnant women screened for HIV showed negative results. CONCLUSION: Hepatitis B carrier rates among pregnant women gradually decreased with a simultaneous increase in the immunity rates. HCV seroprevalence was low and HIV positivity was not encountered in the study population.

Routine first-trimester screening for fetal trisomies in twin pregnancy: cell-free DNA test contingent on results from combined test.

OBJECTIVE: To report on the routine clinical implementation of cell-free DNA (cfDNA) analysis of maternal blood for trisomies 21, 18 and 13, contingent on the results of the first-trimester combined test in twin pregnancy. METHODS: Screening for trisomies 21, 18 and 13 was carried out in 959 twin pregnancies by assessment of a combination of maternal age, fetal nuchal translucency thickness, and serum free ß-human chorionic gonadotropin and pregnancy-associated plasma protein-A at 11-13 weeks' gestation in two UK NHS hospitals. Women in the high-risk group (risk ≥ 1 in 100) were offered the option of invasive testing, cfDNA testing or no further testing, and those in the intermediate-risk group (risk 1 in 101 to 1 in 2500 in the first phase of the study and 1 in 101 to 1 in 500 in the second phase) were offered cfDNA or no further testing. The trisomic status of the pregnancies was determined by prenatal or postnatal karyotyping or examination of the neonates. RESULTS: In 42 (4.4%) of the 959 pregnancies, there was termination, miscarriage or stillbirth with no known karyotype or there was loss to follow-up. The 917 pregnancies with known trisomic status of both twins included six that were discordant for trisomy 21, four that were discordant for trisomy 18 and 907 with no trisomy 21, 18 or 13. Following combined screening, 47 (5.1%), 203 (22.1%) and 667 (72.7%) of the pregnancies were classified as high risk, intermediate risk and low risk, respectively. The high-risk group included five (83.3%) cases of trisomy 21 and three (75.0%) of trisomy 18. The cfDNA test was carried out in 224 pregnancies and results were provided in 214 (95.5%); this group included six pregnancies with trisomy 21, three with trisomy 18 and 206 with no trisomy 21, 18 or 13. The cfDNA test classified correctly as screen positive all six cases of trisomy 21 and two of the three with trisomy 18, and as screen negative for each of the trisomies all 206 unaffected pregnancies. Contingent screening led to prenatal detection of all cases of trisomy 21 and three of four with trisomy 18. CONCLUSION: This study has demonstrated the feasibility of introducing cfDNA testing, contingent on the results of the first-trimester combined test for major trisomies, in a routine population of twin pregnancies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Reference Ranges and Determinants of Thyroid Function During Early Pregnancy: The SELMA Study.

Context: Establishing reference ranges as well as identifying and quantifying the determinants of thyroid function during pregnancy is important for proper clinical interpretation and optimizing research efforts. However, such data are sparse, specifically for triiodothyronine measurements, and most studies do not take into account thyroid antibodies or human chorionic gonadotropin. Objective: To determine reference ranges and to identify/quantify determinants of TSH, free T4 (FT4), free triiodothyronine (FT3), total T4 (TT4), and total triiodothyronine (TT3). Design, Setting, and Participants: This study included 2314 participants of the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study, a population-based prospective pregnancy cohort of mother-child pairs. Reference ranges were calculated by 2.5th to 97.5th percentiles after excluding thyroperoxidase antibody (TPOAb)-positive and/or thyroglobulin antibody (TgAb)-positive women. Intervention: None. Main Outcome Measures: TSH, FT4, FT3, TT4, and TT3 in prenatal serum. Results: After exclusion of TPOAb-positive women, reference ranges were as follows: TSH, 0.11 to 3.48 mU/L; FT4, 11.6 to 19.4 pmol/L; FT3, 3.72 to 5.92 pg/mL; TT4, 82.4 to 166.2 pmol/L; and TT3, 1.28 to 2.92 nmol/L. Additional exclusion of TgAb-positive women did not change the reference ranges substantially. Exposure to tobacco smoke, as assessed by questionnaires and serum cotinine, was associated with lower TSH and higher FT3 and TT3. Body mass index (BMI) and gestational age were the main determinants of TSH (only for BMI), FT4, FT3, TT4, and TT3. Conclusions: We show that the exclusion of TgAb-positive women on top of excluding TPOAb-positive women hardly affects clinical reference ranges. We identified various relevant clinical determinants of TSH, FT4, FT3, TT4, and TT3 that could reflect endocrine-disrupting effects and/or effects on thyroid hormone transport or deiodination.

Seroprevalence of HIV, HTLV, CMV, HBV and rubella virus infections in pregnant adolescents who received care in the city of Belém, Pará, Northern Brazil.

BACKGROUND: Prenatal tests are important for prevention of vertical transmission of various infectious agents. The objective of this study was to describe the prevalence of human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis B virus (HBV), cytomegalovirus (CMV), rubella virus and vaccination coverage against HBV in pregnant adolescents who received care in the city of Belém, Pará, Brazil. METHODS: A cross-sectional study was performed with 324 pregnant adolescents from 2009 to 2010. After the interview and blood collection, the patients were screened for antibodies and/or antigens against HIV-1/2, HTLV-1/2, CMV, rubella virus and HBV. The epidemiological variables were demonstrated using descriptive statistics with the G, χ2 and Fisher exact tests. RESULTS: The mean age of the participants was 15.8 years, and the majority (65.4%) had less than 6 years of education. The mean age at first intercourse was 14.4 years, and 60.8% reported having a partner aged between 12 and 14 years. The prevalence of HIV infection was 0.3%, and of HTLV infection was 0.6%. Regarding HBV, 0.6% of the participants had acute infection, 9.9% had a previous infection, 16.7% had vaccine immunity and 72.8% were susceptible to infection. The presence of anti-HBs was greater in adolescent between 12 and 14 years old (28.8%) while the anti-HBc was greater in adolescent between 15 and 18 years old (10.3%). Most of the adolescents presented the IgG antibody to CMV (96.3%) and rubella (92.3%). None of the participants had acute rubella infection, and 2.2% had anti-CMV IgM. CONCLUSIONS: This study is the first report of the seroepidemiology of infectious agents in a population of pregnant adolescents in the Northern region of Brazil. Most of the adolescents had low levels of education, were susceptible to HBV infection and had IgG antibodies to CMV and rubella virus. The prevalence of HBV, HIV and HTLV was similar to that reported in other regions of Brazil. However, the presence of these agents in this younger population reinforces the need for good prenatal follow-up and more comprehensive vaccination campaigns against HBV due to the large number of women susceptible to the virus.

A retrospective exploratory study of fetal genetic invasive procedures at a University Hospital.

This is a retrospective analysis of the patient demographics and cytogenetic results of patients who underwent prenatal invasive testing for genetic analysis at the Foetal Medicine Division of the Department of Obstetrics and Gynecology, Sri Ramachandra Medical College and Research Institute. The main objective of this study was to characterise the changing trends in indications of pregnant women for foetal karyotyping in a 7-year period. A total of 257 procedures were performed in this period, and there was a significant change in the trend of indications for invasive prenatal diagnosis from an advanced maternal age in 2009 to a positive screen test by 2014. Chromosome abnormalities were observed in 9.8% of the cases, with trisomy 21 being the most frequent finding. The findings demonstrate the changing trends in screening and diagnostic testing in the tertiary care centre, with an acceptance of the first and second trimester maternal serum screening tests as a determinant for high-risk pregnancies. Impact statement What is already known on this subject? Despite the fact that India has one of the world's highest birth rates, there is still no public health care policy for the application of cytogenetic prenatal diagnosis. Nevertheless, we have been offering this test in our university teaching hospital since 2008, allowing us to characterise the changing trends in indications of pregnant women who sought invasive diagnostic procedures for foetal genetic studies. What do the results of this study add? The results of our study show that there were major changes in the common indications for prenatal diagnosis during the study period. In 2009, the main indication was an advanced maternal age, referred to in 31% of the cases, which declined steadily to 5% by 2014. In 2014, 51% of cases opted for a prenatal diagnosis because of a first trimester screen positive result, increasing from 12% in 2009. What are the implications of these findings for clinical practice and/or further research? This data is relevant as it would encourage other tertiary hospitals in developing countries like India to consider extending first trimester screening for all women, regardless of age and educate them on the options of prenatal genetic diagnosis for reassurance.

When ultrasound anomalies are present: An estimation of the frequency of chromosome abnormalities not detected by cell-free DNA aneuploidy screens.

OBJECTIVES: This study characterizes cytogenetic abnormalities with ultrasound findings to refine counseling following negative cell-free DNA (cfDNA). METHODS: A retrospective cohort of pregnancies with chromosome abnormalities and ultrasound findings was examined to determine the residual risk following negative cfDNA. Cytogenetic data was categorized as cfDNA detectable for aneuploidies of chromosomes 13, 18, 21, X, or Y or non-cfDNA detectable for other chromosome abnormalities. Ultrasound reports were categorized as structural anomaly, nuchal translucency (NT) ≥3.0 mm, or other "soft markers". Results were compared using chi squared and Fishers exact tests. RESULTS: Of the 498 fetuses with cytogenetic abnormalities and ultrasound findings, 16.3% (81/498) had non-cfDNA detectable results. In the first, second, and third trimesters, 12.4% (32/259), 19.5% (42/215), and 29.2% (7/24) had non-cfDNA detectable results respectively. The first trimester non-cfDNA detectable results reduced to 7.7% (19/246) if triploidy was detectable by cfDNA testing. For isolated first trimester NT of 3.0-3.49 mm, 15.8% (6/38) had non-cfDNA detectable results, while for NT ≥3.5 mm, it was 12.3% (20/162). For cystic hygroma, 4.3% (4/94) had non-cfDNA detectable results. CONCLUSIONS: Counseling for residual risk following cfDNA in the presence of an ultrasound finding is impacted by gestational age, ultrasound finding, and cfDNA detection of triploidy.