ADAM12 as a marker of trisomy 18 in the first and second trimester of pregnancy

Background. ADAM12 (a disintegrin and metalloprotease 12) is a placentally derived glycoprotein that appears to be involved in growth and differentiation. The maternal serum concentration of ADAM12 appears to be a very good marker of trisomy 21 in the early first trimester when levels are reduced, and in the second trimester around 16–18 weeks levels are elevated. One small preliminary study of first trimester pregnancies with trisomy 18 found reduced levels in the maternal serum, and we examine herein the potential of ADAM12 as a marker of trisomy 18 in both the first and second trimester of pregnancy.

Materials and methods. The concentration of ADAM12 was determined by a time-resolved immunofluorometric assay in 132 first and 12 second trimester cases of trisomy 18, and 389 first and 341 second trimester gestational age-matched control pregnancies. Medians of normal pregnancies were established by polynomial regression and used to determine the population distribution parameters for the trisomy 18 and control groups. Correlation with previously established pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (β-hCG) multiples of the median (MoMs) and nuchal translucency thickness (NT) MoM were determined and used to model the performance of first trimester screening with ADAM12 in combination with other first trimester markers.

Results. The maternal serum concentration of ADAM12 in the first trimester was significantly reduced with a median MoM of 0.829 (p < 0.001) and a mean log₁₀ MoM SD of 0.2663 compared to 0.3353 in the controls. In the second trimester small series ADAM12 was significantly increased with a median MoM of 2.09 (p = 0.001) and a mean log₁₀ MoM SD of 0.2607 compared to 0.4318 in controls. There was a significant correlation of ADAM12 MoM with gestational age (r = 0.510) in trisomy 18 cases, and the median MoM increased from 0.51 at 10 weeks to 1.28 at 13 weeks and 2.09 across the 14–18 week window. ADAM12 was correlated with PAPP-A (r = 0.1918) in the first trimester of cases with trisomy 18 but less so with NT (r = 0.1594) and free β-hCG (r = 0.0938). Modeled detection rates incorporating ADAM12, free β-hCG, and NT were 92% at 1% false positive rate (88% at 0.5%) A combination of all four markers had a detection rate of 96.5% at a false positive rate of 1% (95% at 0.5%).

Conclusion. ADAM12 may be a useful addition to early screening for trisomy 18 alongside other chromosomal anomalies, particularly if biochemical screening can occur before 10 weeks.     

Assessment of sonographer nuchal translucency measurement performance – central tendency and dispersion

Objective.?To assess center and sonographer nuchal translucency (NT) measurements that were performed as part of routine prenatal screening for Down syndrome.

Methods.?Sonographers were assessed for measures of central tendency and dispersion by comparing them with expected population median and dispersion parameters. NT measurements were converted to multiples of the expected NT values according to CRL (NTMoM) and transformed to their log₁₀ equivalent (log₁₀ NTMoM). Central tendency and measurement were assessed by checking whether the median of the NTMoM distribution and SD of the log₁₀ NTMoM distributions were, respectively, within 5% or 10% of the expected median of 1 and SD of 0.1. Assessment was performed using both the Center specific and Fetal Medicine Foundation (FMF) reference NT for Crown rump length (CRL).

Results.?The median NT MoM was 0.95 MoM using the FMF reference and 1.01 MoM when assessed using our center specific reference median. The difference between the center and FMF derived NT MoMs was statistically significantly (p?<?0.0001). NTMoM medians increased over time at a rate of 0.0099 MoM per year while log₁₀ NT MoM measurement dispersement was similar to the 0.1 value expected and decreased by 0.0048 per year.

Conclusion.?Centers should routinely monitor the quality of NT measurements used to estimate Down syndrome screening risk and should provide individualized feedback to sonographers of their measures of central tendency and dispersion to ensure consistent and improved performance. NT reference medians adopted from other populations should be assessed and validated against a centers own measurement distribution.     

Histomorphometric characteristics of first trimester chorionic villi in pregnancies with low serum pregnancy-associated plasma protein-A levels: relationship with placental three-dimensional power doppler ultrasonographic vascularization

Objective.?To evaluate histomorphometric vascular characteristics from samples obtained by chorionic villus sampling (CVS) in pregnancies with low serum pregnancy-associated plasma protein-A (PAPP-A) levels and to relate these findings to three-dimensional (3D) placental volume and power Doppler vascularization.

Methods.?Immediately before CVS, placental 3D-power Doppler ultrasonography was performed at 11?+?0 to 13?+?6 weeks in 12 pregnancies with PAPP-A concentrations <0.3 multiples of median (MoM) as well as in 11 control women. Using a standardized setting placental volume, vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured. Histomorphometric parameters of villi were blindly evaluated with a video-computerized-image-analysis system.

Results.?Pregnancies with low PAPP-A showed a significantly reduced number of capillary vessels per villus cross-section (p?=?0.005) and a smaller capillary diameter (p?=?0.041). Placental vascular indices were significantly related to the number of fetal capillary vessels per villus (VI: r?=?0.51, p?=?0.03; FI: r?=?0.48, p?=?0.04; VFI: r?=?0.56, p?=?0.01).

Conclusions.?Differences in placental vascularization are present in first trimester in pregnancies with low PAPP-A and they are associated to altered 3D placental Doppler indices.     

Maternal serum ADAM12s in the late first trimester of pregnancies with Trisomy 21

BACKGROUND: ADAM12s is a placenta-derived glycoprotein that is involved in growth and differentiation, and has been shown to be a potential first-trimester and second-trimester marker of Trisomy 21 and other aneuploides. Maternal ADAM12s concentrations show a considerable temporal variation with gestational age and here we study the levels at 11-13 weeks of gestation to establish the effectiveness or otherwise at a time when other established markers are used. MATERIALS AND METHODS: Samples collected as part of routine first-trimester screening were retrieved from storage. In total, 46 samples from pregnancies with Trisomy 21 were identified and collected between 11 and 13 weeks of gestation-of these 83% had been identified by combined first-trimester screening. A series of 414 gestational age-matched samples collected during the same period formed the control group. ADAM12s was measured by a new DELFIA assay incorporating two monoclonals (6E6 and 8F8). Results were expressed as weight-corrected multiples of the median (MoM). RESULTS: The median MoM ADAM12s rose from 0.914 at 11 weeks to 1.032 at 13 weeks. CONCLUSIONS: Combining the data from this study and other published studies suggests that ADAM12s is unlikely to be of much additional value when screening for Trisomy 21 in the period 11-13 weeks. More studies are required looking at the potential of ADAM12s prior to 10 weeks.     

Serum placental growth factor and fms-like tyrosine kinase 1 during first trimester in Chinese women with pre-eclampsia – a case–control study

Objective.?To investigate the association between first trimester maternal placental growth factor (PlGF) and fms-like tyrosine kinase 1 (sFlt-1) levels with subsequent development of pre-eclampsia (PE).

Methods.?This is a matched case–control study using stored serum samples collected from non-smoking Chinese women with singleton pregnancies who underwent first trimester screening for aneuploidy. Each case that developed PE was matched with a control whose maternal age, weight, gestational age and date of blood collection were within ±2 years, ±5?kg, ±1 day, and?±2 weeks of the index case, respectively. Non-parametric paired test was used to compare the PlGF and sFlt-1 levels. PlGF and sFlt-1 were transformed to their equivalent multiple of the median (MoM) using the matched control as the expected median value. The 95% confidence interval (CI) of the estimated median PlGF and sFlt-1 MoM in those with PE was determined.

Results.?The median PlGF level in the 27 study cases with PE was lower than that of the matched controls (42.9?pg/ml versus 59.8?pg/ml; p?=?0.001). The median PIGF MoM was 0.71 (95% CI 0.63–0.92). There was no statistically significant difference in sFlt-1 levels between those with PE and their matched control (p?=?0.648). The median sFlt-1 MoM was 1.01 (95% CI 0.65–1.3).

Conclusions.?Women who developed PE had lower serum PlGF levels but normal sFlt-1 levels in the first trimester.     

Maternal serum laeverin (aminopeptidase Q) measured in the first trimester of pregnancy does not predict preeclampsia

Objective: The aim of this study was to compare the laeverin level in maternal serum from first trimester (11–14 weeks) of pregnancy between normal pregnancies and pregnancies that later developed preeclampsia (PE).

Material and methods: This was a case-cohort study. The laeverin concentration was measured in cases with preterm PE (n?=?55), term PE (n?=?95), and a reference group of randomly selected women with normal pregnancy outcome (n?=?200) in stored serum samples collected from the double-test as part of the combined first trimester trisomy 21 screening program. The samples were thawed and analyzed for laeverin. The median gestational age at blood sampling was 77 days (range 57–96 days). Multiple regression analysis was performed to establish a normal median. Concentrations were converted to multiples of the median (MoM) and groups were compared using the Mann–Whitney U-test.

Results: In the reference group, laeverin was significantly correlated with gestational age (r?=?0.18, p?=?.01) and its concentration ranged from 41–393 µg/L. No significant differences in the median laeverin MoM were found between the reference group (1.01 MoM) and cases with preterm PE (0.98 MoM) or term PE (0.96 MoM).

Conclusions: First trimester maternal serum laeverin level cannot be used to predict preeclampsia.     

ADAM12 as a marker of trisomy 18 in the first and second trimester of pregnancy.

BACKGROUND: ADAM12 (a disintegrin and metalloprotease 12) is a placentally derived glycoprotein that appears to be involved in growth and differentiation. The maternal serum concentration of ADAM12 appears to be a very good marker of trisomy 21 in the early first trimester when levels are reduced, and in the second trimester around 16-18 weeks levels are elevated. One small preliminary study of first trimester pregnancies with trisomy 18 found reduced levels in the maternal serum, and we examine herein the potential of ADAM12 as a marker of trisomy 18 in both the first and second trimester of pregnancy. MATERIALS AND METHODS: The concentration of ADAM12 was determined by a time-resolved immunofluorometric assay in 132 first and 12 second trimester cases of trisomy 18, and 389 first and 341 second trimester gestational age-matched control pregnancies. Medians of normal pregnancies were established by polynomial regression and used to determine the population distribution parameters for the trisomy 18 and control groups. Correlation with previously established pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG) multiples of the median (MoMs) and nuchal translucency thickness (NT) MoM were determined and used to model the performance of first trimester screening with ADAM12 in combination with other first trimester markers. RESULTS: The maternal serum concentration of ADAM12 in the first trimester was significantly reduced with a median MoM of 0.829 (p < 0.001) and a mean log10 MoM SD of 0.2663 compared to 0.3353 in the controls. In the second trimester small series ADAM12 was significantly increased with a median MoM of 2.09 (p = 0.001) and a mean log10 MoM SD of 0.2607 compared to 0.4318 in controls. There was a significant correlation of ADAM12 MoM with gestational age (r = 0.510) in trisomy 18 cases, and the median MoM increased from 0.51 at 10 weeks to 1.28 at 13 weeks and 2.09 across the 14-18 week window. ADAM12 was correlated with PAPP-A (r = 0.1918) in the first trimester of cases with trisomy 18 but less so with NT (r = 0.1594) and free beta-hCG (r = 0.0938). Modeled detection rates incorporating ADAM12, free beta-hCG, and NT were 92% at 1% false positive rate (88% at 0.5%) A combination of all four markers had a detection rate of 96.5% at a false positive rate of 1% (95% at 0.5%). CONCLUSION: ADAM12 may be a useful addition to early screening for trisomy 18 alongside other chromosomal anomalies, particularly if biochemical screening can occur before 10 weeks.     

Effect of long-term storage on placental growth factor and fms-like tyrosine kinase 1 measurements in samples from pregnant women

Objective.?To assess the effect of storage time on the stability of placental growth factor (PlGF) and fms-like tyrosine kinase 1 (sFlt-1) levels in frozen serum samples from pregnant women.

Methods.?This is a matched case–control study using fresh and stored serum samples collected at 6, 12, 18, 24, 30 and 36 months prior to the collection of the fresh samples and frozen at –80°C. Forty-eight samples from each of the seven time-groups were matched for non-smoking Chinese, maternal weight, singleton-term pregnancy without major obstetric complications and extracted for PlGF and sFlt-1 assays. Multivariate analysis was performed to assess residual effects of the case-matching procedure. ANOVA was used to assess the effects of storage time.

Results.?Multivariate analysis of the 336 samples indicated that log₁₀PlGF was positively correlated with parity (p?=?0.014) and gestational age (p?=?0.029), while log₁₀sFlt-1 was inversely correlated with parity (p?=?0.018). After correcting for the residual effect of gestation and parity, ANOVA showed no significant difference in PlGF and sFlt-1 levels between the fresh samples and all stored samples (p?=?0.410 and p?=?0.158, respectively).

Conclusions.?Serum PlGF and sFlt-1 levels are stable for at least 3 years when stored at –80°C. Parity is an independent factor of PlGF and sFlt-1 levels. PlGF levels are lower and sFlt-1 levels are higher in nulliparous women compared to multiparous.     

Second trimester maternal serum inhibin-A in fetal anemia secondary to hemoglobin Bart’s disease

Abstract

Objective: To compare the levels of inhibin-A between pregnancies with fetal anemia secondary to Hb Bart’s disease and pregnancies with normal non-anemic fetuses.

Methods: Sixty-five pregnancies at risk of fetal Hb Bart’s disease scheduled for cordocentesis at 18–22 weeks were prospectively recruited into the study. Inhibin-A levels were measured from maternal blood drawn before cordocentesis. Fetal blood samples were collected for fetal Hb typing and hemoglobin (Hb) levels.

Results: Maternal serum inhibin-A was significantly higher in women with fetal Hb Bart’s disease than those with unaffected fetuses (1.03?MoM (multiple of median) and 0.75 MoM, respectively, p?=?0.001). The relationship between maternal serum inhibin-A and fetal Hb level was a quadratic equation; inhibin-A?=?5.248?–?9.415(Hb)?+?4.919(Hb)² (r²?=?0.274, p?<?0.001). Maternal serum inhibin-A did not correlate with cardiomegaly but was significantly associated with placental thickness; inhibin-A?=?1.372?–?0.751(Pl)?+?0.214(Pl)² (r²?=?0.237, p?=?0.007).

Conclusions: Maternal serum inhibin-A levels were significantly higher in pregnancies with fetal Hb Bart’s disease. The elevation of inhibin-A was likely to be a consequence of fetal anemia and placentomegaly. Since inhibin-A is commonly used as a component of quadruple test; the calculated risk of Down’s syndrome may be unreliable in pregnancies with fetal Hb Bart’s disease or possible fetal anemia.     

ADAM 12 as a second-trimester maternal serum marker in screening for Down syndrome

BACKGROUND: ADAM 12 is a placenta-derived glycoprotein that is involved in growth and differentiation. The maternal serum concentration of ADAM 12 is a potential first-trimester maternal serum marker of Down syndrome (DS). Here we examine the potential of ADAM 12 as a second-trimester maternal serum marker of DS. MATERIALS AND METHODS: The concentration of ADAM 12 was determined in gestational week 14-19 in 88 DS pregnancies and 341 matched control pregnancies. Medians of normal pregnancies were established by polynomial regression and the distribution of log(10) MoM ADAM 12 values in DS pregnancies and controls determined. Correlations with alpha-fetoprotein (AFP) and free beta-human chorionic gonadotrophin (free beta-hCG) were established and used to model the performance of maternal serum screening with ADAM 12 in combination with other second-trimester serum markers. RESULTS: The ADAM 12 maternal serum concentration was significantly increased with a median MoM of 1.85 and a mean log(10) MoM (SD) of 0.268 (0.2678) compared to a mean log(10) MoM (SD) of 0.013 (0.4318) in controls. ADAM 12 correlated with maternal weight and ethnicity (with the serum concentration increased in Afro-Caribbeans), but neither with maternal age nor gestational age, and only marginally with AFP (r(DS) = 0.078, r(controls) = 0.093) and free beta-hCG (r(DS) = 0.073, r(controls) = 0.144. The increase in detection rate-for a false positive rate of 5%--by adding ADAM 12 to the double test (AFP + free beta-hCG) was 4%, similar to that of adding uE3 to the double test. CONCLUSION: ADAM 12 is an efficient second-trimester marker for DS. Further studies should be conducted to determine whether it may be a useful additional or alternative marker to those currently used in the second-trimester.     

Association of maternal serum α-fetoprotein with persistent placenta previa

Objective: To evaluate the relationship between maternal serum α-fetoprotein (MSAFP) and the risk of persistent placenta previa.

Methods: We conducted a retrospective cohort study of singleton pregnancies with sonographic evidence of placenta previa at 15?–?20 weeks' gestation, between October 1991 and August 2000. Only pregnancies with MSAFP determination at 15?–?20 weeks' gestation and non-anomalous live-born infants ??24 weeks' gestation were included. Pregnancies in which Cesarean delivery was performed for placenta previa were considered persistent; this was the primary outcome.

Results: Of 275 women with previa at 15?–?20 weeks' gestation, 33 (12%) had previa at delivery. Trend analysis revealed a greater likelihood of persistent previa with increasing MSAFP values (p?=?0.01). Mid-trimester MSAFP <?1 multiple of the median (MoM) was associated with a decreased incidence of persistence of 4%, significantly less than the risk at ??1 MoM (16%; p?=?0.01).

Conclusions: There is an association between increasing MSAFP values and greater likelihood of persistent placenta previa. An MSAFP value <?1 MoM is associated with a reduction in the risk of persistence of previa to delivery.     

Preeclampsia in twin pregnancies: association with selective intrauterine growth restriction

Objective: To identify the association between preeclampsia (PE) and selective intrauterine growth restriction (sIUGR) in twin pregnancies.

Methods: This was a retrospective cohort study of 1004 twin pregnancies from 2008 to 2014. We specifically compared the incidence, clinical characteristics and outcomes of PE between sIUGR and normal-growth twin pregnancies.

Results: PE occurred more frequently in sIUGR pregnancies [29.0% (51/176)] than in normal-growth twin pregnancies [13.1% (99/756), p?<?0.001, adjusted odds ratio 3.29]. Among sIUGR, the incidence of PE was significantly higher in dichorionic (DC) pregnancies (37.5%, 30/80) than in monochorionic (MC) pregnancies (21.9%, 21/96). The rates of onset at <32 weeks (p?=?0.045) and of severe PE (p?=?0.025) were higher in sIUGR pregnancies with PE. The systolic blood pressure was also higher in sIUGR pregnancies with PE (152.6?±?11.8?mmHg) than in normal-growth pregnancies with PE (148.0?±?8.2?mmHg) (p?=?0.042). Additionally, more sIUGR pregnancies were delivered at 32–36 weeks (p?=?0.001), and fewer were delivered at ≥36 weeks (p?<?0.001). Moreover, the prevalence of severe neonatal asphyxia was higher in sIUGR pregnancies with PE than in normal-growth pregnancies with PE (8.8% versus 2.5%, p?=?0.020).

Conclusions: sIUGR is associated with increased odds of developing severe PE in twin pregnancies, leading to poorer perinatal outcomes.     

Fetal cerebral and umbilical Doppler in pregnancies complicated by late-onset placental abruption

Objective: To evaluate whether changes in the cerebroplacental Doppler and birth weight (BW) suggestive of chronic fetal hypoxemia, precede the development of late-onset placental abruption (PA) after 32 weeks.

Methods: In a multicenter retrospective study, the Doppler examinations of the fetal umbilical artery (UA) and middle cerebral artery (MCA) recorded after 32 weeks were collected in pregnancies subsequently developing PA. The BW centiles were calculated and the MCA pulsatility indices (PI), and UA PI were converted into multiples of the median (MoM). Afterwards, a comparison was made with a group of fetuses, which did not develop PA. Logistic regression was used to adjust for potential confounders and evaluate the feasibility of the prediction model.

Results: Pregnancies complicated by late-onset PA (n?=?31) presented lower MCA PI (p?=?0.015) and were smaller (p?n?=?1294). Logistic regression analysis indicated that cerebral vasodilation was more important than umbilical flow in the explanation of PA (MCA PI OR?=?0.106, p?=?0.014 and UA PI OR 1.901, p?=?0.32). In addition, the influence of BW exerted was residual (BW centile OR?=?0.989, p?=?0.15).

Conclusions: Fetuses developing late-onset PA demonstrate significant cerebral vasodilation with scarce placental dysfunction, suggesting the existence of some kind of chronic hypoxemia that follows the late-onset pattern.     

First-trimester ADAM12s as early markers of trisomy 21: a promise still unfulfilled?

BACKGROUND: Here we study the levels of ADAM12s prior to and after 10 weeks of gestation to establish further the effectiveness or otherwise of ADAM12s as an early screening marker. MATERIALS AND METHODS: Samples collected as part of routine first-trimester screening were retrieved from storage at - 80 degrees C. In total, 55 samples from pregnancies with trisomy 21 were identified, 31 collected between the 6th and 9th weeks of gestation and 24 collected after the 10th week. A series of 567 gestational age-matched samples collected during the same period formed the control group. RESULTS: The median, multiples of the median (MoM) ADAM12s, at a median gestation of 10.0 weeks was 0.66, which was significantly lower than in the controls (p = < 0.001) when compared by Mann-Whitney test. The median MoM in those cases (n = 31) collected prior to 10 weeks was 0.618 MoM at a median gestation of 9.1 weeks. In those collected prior to 9 weeks (n = 14) the median was 0.596 at a median gestation of 8.6 weeks. CONCLUSIONS: The data from this study does not support data from a previous study showing ultra-low levels of ADAM12s in pregnancies affected by trisomy 21 prior to 10 weeks of gestation.     

Maternal serum anti-Müllerian hormone at 11–13 weeks’ gestation in the prediction of preeclampsia

Objective: To investigate the potential value of maternal serum anti-Müllerian hormone (AMH) at 11–13 weeks’ gestation in the prediction of preeclampsia (PE).

Methods: The serum concentration of AMH was measured at 11–13 weeks’ gestation in cases of PE (n?=?50) and normotensive controls (n?=?150). Backward stepwise multiple regression analysis was used to determine which of the factors amongst the maternal characteristics and gestation were significant predictors of the serum AMH in the control group and from the regression model the value in each case and control was expressed as a multiple of the expected median (MoM).

Results: In normotensive pregnancies, the maternal serum concentration of AMH is higher in Afro-Caribbean than in Caucasian women and in smokers than in non-smokers. In the PE group, the median serum concentration of AMH was significantly higher than in the controls (2.140?ng/L, IQR 1.968–2.273 versus 2.062?ng/L, IQR 1.938–2.181; p?=?0.025), but the median MoM value of AMH was not significantly different between the PE group and the controls (1.040, IQR 0.941–1.081 versus 0.995, IQR 0.939–1.065, p?=?0.147).

Conclusions: Maternal serum AMH is not an effective early predictor for PE.     

First trimester maternal serum pregnancy-associated plasma protein-A is a predictive factor for early preterm delivery in normotensive pregnancies

Abstract

In this study, we investigated whether the concentrations of pregnancy-associated plasma protein-A (PAPP-A) or free β-hCG (fβhCG) in the first trimester can identify women at increased risk of subsequent preterm delivery in the absence of hypertensive disorders. Preterm and early preterm deliveries are defined as those deliveries before completing 37 and 34 weeks, respectively. A total of 868 women were enrolled into this study. According to the level of the markers, the patients were evaluated in three groups: 1 – maternal serum level ≤5th percentile, 2 – between 5th and 95th percentiles, 3 – ≥95th percentile. In the group of patients with a PAPP-A level ≤5th percentile [≤0.35 multiples of the median (MoM)], mean gestational age (GA) at delivery, mean birth weight and the number of the cases with early preterm delivery were significantly lower than the others. Mean level of PAPP-A was significantly lower in cases with early preterm than term deliveries (0.58?±?0.32 versus1.09?±?0.69; p?=?0.01). Maternal serum level of fβhCG did not show significant difference between these groups (0.84?±?0.45 versus 1.17?±?0.77; p?=?0.15). Low levels of maternal serum PAPP-A (≤0.35 MoM) (Odds ratio?=?7; 95% confidence interval 1.8–27.7; p?=?0.0048) significantly predicted early preterm delivery in normotensive pregnancies. Women with low levels of PAPP-A at first trimester have a higher risk of early preterm delivery even in the absence of hypertensive disorders.     

The mid-gestation triple test profile among women diagnosed with vasa previa

Purpose: To assess the mid-trimester triple test biomarkers among women diagnosed with vasa previa (VP).

Methods: The study included 43 singleton pregnancies diagnosed with vasa previa between the years 1988 and 2011. The mid-gestation screening test for Down syndrome was calculated from the combination of triple serum markers and maternal age, and expressed as a multiple of the gestation specific normal mean (MoM). Reference MoM values were calculated from the local population. The levels of mid-gestation maternal serum alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) of patients with VP were compared with control reference group.

Results: The mean hCG and αFP levels of women diagnosed with VP was significantly higher compared to control reference group (1.42 versus 0.99 MoM; p?p?3 levels between these two groups (0.99 versus 0.98 MoM; p?=?.71).

Conclusions: Our findings suggest that increased mid-gestation hCG and AFP were found among pregnancies complicated with VP. Clinicians should consider targeted scanning of pregnant women with risk factors for VP, including unexplained high maternal levels of hCG and αFP of the triple test, while conducting mid-gestation anomaly scan.     

Macrophage infiltration and stress-signaling in omental and subcutaneous adipose tissue in diabetic pregnancies

Abstract

Objective: To examine if, as in obesity, pregnancies complicated by gestational diabetes mellitus (GDM) exhibit increased macrophage infiltration and activated MAP-kinases in omental adipose tissue.

Methods: Paired omental (OM) and abdominal subcutaneous (SC) fat samples were collected from 11 GDM and 20 normal pregnancies during cesarean delivery. Tissues were stained to detect macrophages, and analyzed to assess MAP-kinases.

Results: OM had higher macrophage counts than SC in GDM (6.10?±?2.20 versus 2.53?±?1.45, p?=?0.04), but not in normal pregnancies (p?=?0.346). GDM pregnancies had more macrophages than normal pregnancies in OM (6.10?±?2.20 versus 1.29?±?0.55, p?=?0.01), while only a trend was observed in SC fat (p?=?0.08). Significant correlation (R?=?0.619, p?=?0.005) was observed between OM-macrophage infiltration and insulin resistance. Using multivariate analysis, only obesity independently associated with GDM. Expression of total p38MAP-kinase was higher in OM versus SC in both normal and GDM pregnancies, without significant differences between these groups. However, expression of activated p-p38MAP-kinase, and its upstream kinase MKK4, was comparable between fat depots.

Conclusion: GDM pregnancies demonstrate increased macrophage infiltration to OM fat, correlating with higher insulin resistance. As in non-pregnant-patients obesity and OM macrophage infiltration may be on the same causal pathway, leading to GDM. Yet, this occurs without activation of p38MAP-kinase signaling.     

Influence of fetal acidemia on fetal heart rate analyzed by computerized cardiotocography in pregnancies with placental insufficiency

Abstract

Objective: To determine the influence of fetal acidemia on fetal heart rate (FHR) parameters analyzed by computerized cardiotocography (cCTG) in pregnancies with placental insufficiency.

Methods: This was a cross-sectional study of 46 pregnancies with placental insufficiency between 26 and 34 weeks gestation by abnormal umbilical artery Doppler [pulsatility index (PI)?>?95th percentile].

Results: Twenty fetuses had acidemia at birth, pH?<?7.20 (43.5%) and 26 had normal pH (56.5%). In the analysis of FHR parameters, fetal movements (FM) per hour was significantly lower in the group with acidemia (median?=?2) when compared with the group with normal pH (median?=?15, p?=?0.019). The values of pH correlated positively with FM (ρ?=?0.35; p?=?0.019, 95% CI: 0.061 to 0.577) and basal FHR (ρ?=?0.37, p?=?0,011, 95% CI: 0.090 to 0.597) and negatively with the ductus venosus (DV) PI for veins (PIV) z-score (ρ?=??0.31, p?=?0,036, 95% CI: ?0.550 to ?0.021). Logistic regression showed that the DV PIV z-score (p?=?0.0232) and basal FHR (p?=?0.0401) were independent variables associated with acidemia at birth.

Conclusions: The present results suggest that cCTG parameters may be useful in the management of cases with early onset placental insufficiency in association with Doppler velocimetry assessment, and that basal FHR and DV-PIV are most clearly in association with acidemia at birth.     

Maternal cardiovascular profiling in the first trimester of pregnancies complicated with gestation-induced hypertension or fetal growth retardation: a pilot study

Abstract

Objective: In this study, we determine whether maternal cardiovascular (CV) profiling can detect first trimester differences between women with uncomplicated pregnancies (UP) and those who will develop gestational hypertensive disorders (GHD) or normotensive fetal growth retardation (FGR).

Methods: Cardiac, arterial, and venous function were evaluated in 242 pregnant women around 12 weeks of gestation, using impedance cardiography (ICG) and combined electrocardiogram – Doppler ultrasonography. After postnatal determination of gestational outcome, first trimester measurements were compared between groups using Mann–Whitney U test for continuous data or Fisher’s Exact test for categorical variables (SPSS 20.0).

Results: Compared to UP, first trimester aortic flow velocity index [71?±?0.96 versus 61?±?4.91 1/1000/s (p?=?0.016)], acceleration index [133?±?2.25 versus 106?±?11.26 1/100/s² (p?=?0.023)] and Heather index [23.1?±?0.35 versus 19.2?±?1.70?Ω/s² (p?=?0.019)] were lower in GHD pregnancies, and first trimester stroke volume [77?±?1.16 versus 67?±?3.97?ml (p?=?0.033)] and cardiac output [7.3?±?0.10 versus 6.2?±?0.31?l/min (p?=?0.025)] were lower in FGR pregnancies.

Conclusions: Maternal CV function in the first trimester of pregnancy differs between UP and those destined to develop GHD or FGR. This can be assessed with non-invasive maternal CV profiling, opening perspectives for the application of this technique in early gestational screening for GHD and FGR.