CA 125 Levels in Chromosomally Abnormal Pregnancies

CA 125 levels have been measured in the amniotic fluid of 86 gravidas between 14 and 20 weeks gestation as well as in 18 women at term, all carrying chromosomally normal fetuses; in 36 gestations, the samples were paired with maternal serum specimens. These controls were then compared with the amniotic fluid values in pregnancies of karyotype trisomy 21 (n = 24), trisomy 18 (n = 7), sex chromosome trisomy (n = 5), and sex chromosome monosomy (n = 2), and in the maternal serum of 4 trisomy 21 pregnancies, in an effort to determine if CA 125 could act as a marker for these chromosomal anomalies. Results indicated no significant difference in the amniotic fluid measurements at the time of genetic amniocentesis in normal gestations (5,064 U/ml) and trisomy 21 gestations (4,864 U/ml). The sex chromosome anomalies, too, were not different. Alternatively, the values in trisomy 18 pregnancies were significantly lower (3,154 U/ml; P < 0.05) than controls. There appeared to be no significant correlation between the concurrently measured maternal serum and amniotic fluid levels of CA 125 either at mid-trimester (5,056 U/ml vs. 9.8 U/ml; r = 0.04) or at term (920 U/ml vs. 14.9 U/ml; r = 0.03).     

Second trimester maternal plasma and amniotic fluid adipokines in women who will develop gestational diabetes mellitus

Abstract

Objective: To study the adipokines concentration and glucose homoeostasis in the early-second trimester of women who will develop gestational diabetes mellitus (GDM).

Materials and methods: Maternal plasma and fetal amniotic fluid samples were prospectively collected between 2006 and 2007 at the time of mid-trimester amniocentesis. Eight patients found to be affected by GDM were compared with 10 control patients with a normal pregnancy course. Adipokines leptin and adiponectin, as well as insulin and glucose concentration both in amniotic fluid and maternal plasma were compared between cases and controls. HOMA-IR (homeostatic model assessment for insulin resistance) was also calculated both for amniotic fluid and maternal serum.

Results: The amniotic fluid adiponectin concentration was higher in women who would develop GDM than in controls (29.9?ng/ml, 95% CI 26.7–49.8 ng/ml, versus 14.9 ng/ml, 95% CI 13.5–18.8 ng/ml), p?<?0.05). No difference was shown for leptin both in amniotic fluid and maternal serum. Insulin concentrations in the amniotic fluid were found to be lower in GDM than in controls, while HOMA-IR-index resulted lower in amniotic fluid and higher maternal serum (p?<?0.05).

Conclusions: Our data suggests that an earlier alteration in the fetal glucose metabolism will precede the glucose dysmetabolism in pregnancies later complicated by GDM.     

Correlation between maternal serum-amniotic fluid anti-angiogenic factors and uterine artery Doppler indices

Purpose: Elevated sFlt-1 and sEng is usually a clue for impending preeclampsia and intrauterine growth restriction. Likewise, uterine artery Doppler ultrasound is being investigated for prediction of similar conditions. In this study, we aimed to explore the possible relations of these two proteins in different body compartments with uterine artery Doppler indices (UtAD) in a healthy second trimester obstetric population.

Methods: Levels of sFlt-1 and sEng were measured in serum and amniotic fluid samples of 43 patients. UtAD were measured on the days of sample collections. Findings were then analyzed for possible correlation.

Results: There was a positive correlation between the levels of maternal serum sFlt-1 (MSsFlt-1) and sEng levels (MSsEng) (r=?0.516, pr=??0.371, p=?0.016). No correlation was found between UtAD and studied protein levels in amniotic fluid. Mean MSsFlt-1 level was 305.2?±?220.1?pg/ml and mean AFsFlt-1 was 48.9?±?11.8?ng/ml. Mean MSsEng level was 4.5?±?1.3?ng/ml, mean AFsEng level was found 0.7?±?0.3?ng/ml. Mean values for UtAD were 1.3?±?0.4, 0.6?±?0.1 and 3.5?±?1.3 for PI, RI, and S/D, respectively.

Conclusion: In normal second trimester pregnancies, there is a positive correlation between serum levels of sFlt-1 and sEng levels. Amniotic fluid levels of sEng and sFlt-1 are not correlated with UtAD in uncomplicated pregnancies.     

The association of second trimester biomarkers in amniotic fluid and fetal outcome

Objective: To identify the level of amniotic fluid lactate (AFL), placental growth factor (PLGF), and vascular endothelial growth factor (VEGF) at second trimester amniocentesis, and to compare levels in normal pregnancies with pregnancies ending in a miscarriage, an intrauterine growth restricted fetus (IUGR) or decreased fetal movements.

Study design: A prospective cohort study. Amniotic fluid was consecutively collected at amniocentesis in 106 pregnancies. Fetal wellbeing at delivery was evaluated from medical files and compared with the levels of AFL, VEGF, and PLGF at the time of amniocentesis.

Results: The median level of AFL was 6.9?mmol/l, VEGF 0.088?pg/ml, and PLGF 0.208?pg/ml. The median levels of AFL in pregnancies ended in miscarriage were significantly higher (10.7?mmol/l) compared to those with a live new-born (6.9?mmol/L, p?=?.02). The levels of VEGF (p?=?.2) and PLGF (p?=?.7) were not affected. In pregnancies with an IUGR, the median level of AFL was higher compared to those with normal fetal growth (p?=?.003). No differences VEGF (p?=?.5), but significant lower PLGF were found in IUGR pregnancies (p?=?.03).

Conclusions: Pregnancies ending in a miscarriage or with IUGR had significantly higher median values of AFL but lower values of PLGF in the amniotic fluid at the time of second trimester amniocentesis compared to normal pregnancies.     

Amniotic fluid calreticulin in pregnancies complicated by the preterm prelabor rupture of membranes

Objective: This study aimed to determine the amniotic fluid calreticulin concentrations in women with the preterm prelabor rupture of membranes (PPROM) based on the microbial invasion of the amniotic cavity (MIAC), intraamniotic inflammation (IAI) and microbial-associated IAI.

Methods: One hundred sixty-eight women with singleton pregnancies were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis and were assayed for calreticulin concentrations by ELISA. IAI was defined as an amniotic fluid interleukin-6 concentration?>?745?pg/ml. Microbial-associated IAI was defined as the presence of both MIAC and IAI.

Result: Women with MIAC (with MIAC: median 54.4?ng/ml, versus without MIAC: median 32.6?ng/ml; p?<?0.0001), IAI (with IAI: median 66.8?ng/ml, versus without IAI: median 33.0?ng/ml; p?<?0.0001) and microbial-associated IAI (with microbial-associated IAI: median 82.5?ng/ml, versus without microbial-associated IAI: median 33.7?ng/ml; p?<?0.0001) had higher concentrations of calreticulin than women without these complications. An amniotic fluid calreticulin concentration of 81.4?ng/ml was found to be the best cutoff point for identifying women with microbial-associated IAI.

Conclusions: The presence of microbial-associated IAI is associated with increased amniotic fluid calreticulin concentrations. Calreticulin seems to be a promising marker for the early identification of PPROM complicated by microbial-associated IAI.     

Resistin in amniotic fluid and its association with intra-amniotic infection and inflammation

Objective. Intra-amniotic infection/inflammation (IAI) is one of the most important mechanisms of disease in preterm birth. Resistin is an adipocytokine that has been linked to insulin resistance, diabetes, obesity and inflammation. The objective of this study was to determine if resistin is present in amniotic fluid (AF) and if its concentration changes with gestational age, in the presence of labour, and in IAI in patients with spontaneous preterm labour (PTL) and intact membranes, preterm prelabour rupture of membranes (PPROM) and clinical chorioamnionitis.

Study design. This cross-sectional study included 648 patients in the following groups: (1) women in the mid-trimester of pregnancy (14–18 weeks) who underwent amniocentesis for genetic indications and delivered a normal neonate at term (n = 61); (2) normal pregnant women at term with (n = 49) and without (n = 50) spontaneous labour; (3) patients with an episode of PTL and intact membranes who were classified into: (a) PTL who delivered at term (n = 153); (b) PTL who delivered preterm (<37 weeks gestation) without IAI (n = 108); and (c) PTL with IAI (n = 84); (4) women with PPROM with (n = 47) and without (n = 44) IAI; and (5) patients with clinical chorioamnionitis at term with (n = 22) and without (n = 30) microbial invasion of the amniotic cavity. Resistin concentration in AF was determined by enzyme-linked immunoassay. Non-parametric statistics were used for analyses.

Results. (1) Resistin was detected in all AF samples; (2) the median AF resistin concentration at term was significantly higher than in the mid-trimester (23.6 ng/mL vs. 10 ng/mL; p < 0.001); (3) among patients with PTL, the median AF resistin concentration was significantly higher in patients with IAI than in those without IAI (144.9 ng/mL vs. 18.7 ng/mL; p < 0.001) and those with PTL and intact membranes who delivered at term (144.9 ng/mL vs. 16.3 ng/mL; p < 0.001); (4) patients with PPROM with IAI had a significantly higher median AF resistin concentration than those without IAI (132.6 ng/mL vs. 13 ng/mL; p < 0.001); (5) no significant differences were observed in the median AF resistin concentration between patients with spontaneous labour at term and those at term not in labour (28.7 ng/mL vs. 23.6 ng/mL; p = 0.07); and (6) AF resistin concentration ≥37 ng/mL (derived from a receiver-operating characteristic curve) had a sensitivity of 85.4% and a specificity of 94.3% for the diagnosis of intra-amniotic inflammation.

Conclusions. Resistin is a physiologic constituent of the AF, and its concentrations in AF: (1) are significantly elevated in the presence of IAI; (2) increase with advancing gestation; and (3) do not change in the presence of spontaneous labour at term. We propose that resistin may play a role in the innate immune response against intra-amniotic infection.     

Amniotic fluid CD200 levels in pregnancies complicated by preterm prelabor rupture of the membranes

Abstract

Objective: To determine the amniotic fluid CD200 levels in uncomplicated pregnancies and in preterm prelabor rupture of the membranes (PPROM) according to microbial invasion of the amniotic cavity and histological chorioamnionitis and its association with neonatal outcomes.

Methods: One hundred and fifty-nine women with singleton pregnancies were included in this study. Amniotic fluid was collected, and CD200 levels were determined using ELISA.

Results: No difference was found in CD200 levels between women in the second trimester and women at term without labor. Women at term with labor had higher CD200 levels than women in the second trimester and women at term without labor. The presence of funisitis in PPROM pregnancies was associated with higher CD200 levels independent of gestational age (with funisitis: median 197.5?pg/mL versus without funisitis: median 61.0?pg/mL; p?=?0.003). The need for tracheal intubation and the development of bronchopulmonary dysplasia were associated with higher CD200 levels.

Conclusions: Amniotic fluid CD200 levels remained stable in advanced pregnancy and they were increased during parturition. Elevated CD200 levels in the presence of funisitis suggest the involvement of negative regulatory mechanisms of innate immunity. CD200 may play a role in the development of pulmonary aspects of neonatal morbidity.     

Amniotic fluid concentrations of soluble scavenger receptor for hemoglobin (sCD163) in pregnancy complicated by preterm premature rupture of the membranes and histologic chorioamnionitis

Objective.?To determine changes in the amniotic fluid, soluble form of scavenger receptor for hemoglobin (sCD163) concentrations during advancing gestation, and in patients with preterm premature rupture of membranes (PPROM) complicated by histological chorioamnionitis were studied.

Methods.?One hundred and fifty-two women with singleton pregnancies were enrolled. The concentration of sCD163 in amniotic fluid was determined using sandwich enzyme immunoassay technique.

Results.?Women in the midtrimester had a significantly higher median amniotic fluid sCD163 concentration than those at term not in labor (308 ng/ml vs. 217 ng/ml; p?=?0.04). Patients with PPROM and histological chorioamnionitis had a higher median amniotic fluid sCD163 level than those with PPROM without histological chorioamnionitis (885 ng/ml vs. 288 ng/ml; p?<?0.0001).

Conclusions.?Amniotic fluid sCD163 concentrations decrease with advancing gestation. Amniotic fluid sCD163 concentrations are significantly higher in women with PPROM between 24 and 36 gestational weeks with histological chorioamnionitis than those without histological signs of inflammation.     

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.     

Elevated amniotic fluid leptin levels in early second trimester are associated with earlier delivery and lower birthweight in twin pregnancy

OBJECTIVE: To explore the possibility of using early second trimester amniotic fluid leptin levels as a predictor of pregnancy outcome in twin pregnancy. STUDY DESIGN: Amniotic fluid leptin levels from 18 twin-pregnant women in early second trimester were analyzed for their correlation with gestational age at delivery and fetal birthweight. Leptin levels in 16 amniotic fluid samples collected from small for gestational age (SGA) twin pregnancies were compared with those in 20 amniotic fluid samples collected from non-SGA twin pregnancies. RESULTS: A significant correlation was observed between amniotic fluid leptin levels and gestational age at delivery (r = 0.71, p < 0.001) as well as fetal birthweight (r = 0.72, p < 0.001). There was also a significant correlation between gestational age at delivery and fetal birthweight (r = 0.92, p < 0.001). The average gestational age at delivery was 30.4 +/- 1.4 weeks in the SGA group, with a mean birthweight of 1552 +/- 200 g at delivery. For the non-SGA group, the values were 37.3 +/- 0.5 weeks and 2759 +/- 115 g ( p < 0.001), respectively. Amniotic fluid leptin levels were found to be significantly higher ( p < 0.001) for women in the SGA group (11.4 +/- 1.5 ng/mL) than for those in the non-SGA group (5.4 +/- 0.5 ng/mL). CONCLUSION: Higher amniotic fluid leptin levels in early second trimester were associated with both lower gestational age at delivery and lower birthweight. Our results suggest that amniotic fluid leptin levels in early second trimester may be a good marker for the prediction of perinatal complications in twin pregnancy.     

The significance of a positive second trimester serum screen for trisomy 18

Objectives.?We designed this study to estimate the proportion of fetuses in pregnancies with positive second trimester serum screens for trisomy 18 who actually have trisomy 18, to estimate the proportion of women with trisomy 18 who have a negative serum screen, and to assess the role of ultrasound in the diagnosis of trisomy 18.

Methods.?Retrospective study of two cohorts of pregnant women in 2004 and 2005: (1) those with a second trimester serum screen positive for trisomy 18 and (2) those with fetuses having trisomy 18.

Results.?There were 93 women with positive serum screens for trisomy 18. Of these, only three had a fetus with trisomy 18. There were five other cases of trisomy 18, three of which had a negative second trimester serum screen for trisomy 18. All fetuses with trisomy 18 had multiple major structural abnormalities detected on targeted genetic sonography.

Conclusions.?A positive second trimester serum screen has a poor sensitivity and poor prediction for trisomy 18. Trisomy 18 is highly unlikely if a woman with a positive screen for trisomy 18 has no fetal abnormalities detected on targeted genetic sonography. Women with a positive second trimester serum screen for trisomy 18 should be offered genetic sonography, and the practice of routine amniocentesis for all women with a positive screen should be discouraged when targeted genetic sonography is available.     

Relationship of maternal serum resistin and visfatin levels with gestational diabetes mellitus

Introduction: Adiponectin, resistin and visfatin are thought to play role in the pathophysiology of gestational diabetes (GDM). In this study, we aimed to investigate the association of maternal second trimester serum resistin and visfatin levels with GDM.

Materials and methods: Screening and diagnosis for GDM was performed between the 24–28th gestational weeks. About 40 women diagnosed with GDM and 40 non-diabetic women constituted the study and control groups, respectively. Groups were compared for second trimester maternal serum resistin, visfatin and HbA1c levels, HOMA-IR and postpartum 75?g OGTT results.

Results: Mean serum resistin (p?=?0.071) and visfatin (p?=?0.194) levels were similar between the groups. However, mean BMI (p?=?0.013), HOMA-IR (p?=?0.019), HbA1c (p?p?=?0.037) were significantly higher in GDM group compared to controls. Type 2 diabetes and impaired glucose tolerance were detected in 2 (5%) and 7 (20%) women in the GDM group, respectively, with 75?g OGTT performed at the postpartum 6th week. Resistin levels of patients with GDM and postpartum glucose intolerance were higher than those with GDM but no postpartum glucose intolerance (p?=?0.012). Visfatin levels in the GDM group showed a positive correlation with biparietal diameter, head circumference, abdominal circumference and femur length (p?Conclusion: Maternal serum resistin and visfatin levels are unchanged in GDM. In patients with GDM, second trimester resistin levels may be predictive for postpartum glucose intolerance and second trimester visfatin levels may be related with fetal biometric measurements. Further larger studies are needed.     

Subarachnoid space diameter in chromosomally abnormal fetuses at 11–13 weeks’ gestation

Objectives: To examine the subarachnoid space diameters in chromosomally abnormal fetuses at 11–13 weeks’ gestation.

Methods: Stored three-dimensional (3D) ultrasound volumes of the fetal head at 11–13 weeks’ gestation from 407 euploid and 88 chromosomally abnormal fetuses (trisomy 21, n?=?40; trisomy 18, n?=?19; trisomy 13, n?=?7; triploidy, n?=?14; Turner syndrome, n?=?8) were analyzed. The subarachnoid space diameters, measured in the sagittal and transverse planes of the fetal head, in relation to biparietal diameter (BPD) in each group of aneuploidies was compared to that in euploid fetuses. A total of 20 head volumes were randomly selected and all the measurements were recorded by two different observers to examine the interobserver variability in measurements.

Results: In euploid fetuses, the anteroposterior, transverse and sagittal diameters of the subarachnoid space increased with BPD. The median of the observed to expected diameters for BPD were significantly increased in triploidy and trisomy 13 but were not significantly altered in trisomies 21 and 18 or Turner syndrome. In triploidy, the subarachnoid space diameters for BPD were above the 95th centile of euploid fetuses in 92.9% (13 of 14) cases. The intraclass reliability or agreement was excellent for all three subarachnoid space diameters.

Conclusion: Most fetuses with triploidy at 11–13 weeks’ gestation demonstrate increased subarachnoid space diameters.     

Nuchal translucency and cardiac abnormalities in euploid singleton pregnancies

Abstract

Objective: To investigate different cut-off levels of nuchal translucency (NT) to predict abnormal cardiac findings (ACF) in second trimester ultrasound examination and confirmed postnatal congenital heart defects (CHD) in euploid pregnancies.

Methods: A retrospective analysis was performed on singleton pregnancies examined in our ultrasound units from 2006 to 2011. Fetuses with an abnormal karyotype were excluded. Different cut-off levels of NT thickness were analyzed to evaluate its performance to detect the ACF on second trimester ultrasound (2nd US) examination and also the CHD detected in neonatal follow-up evaluation of ACF cases.

Results: Of the 12?840 cases, a total number of 8541 euploid pregnancies were included in the study. Thirty-three had ACFs detected by 2nd US (3.86/1000). The mean NT thickness was found to be higher in fetuses with ACFs (p?<?0.0001). Of 33 ACFs, 17 (52%, 1.99/1000) had major CHDs in neonatal follow-up. The area under the ROC curves for NT thickness to predict ACFs and CHDs were 0.67 and 0.65, respectively.

Conclusions: Higher NT thickness is associated with higher risk of ACF. NT is a weak predictor of ACF and major CHD; however, fetuses with an unexplained increase in NT measurement should be referred for further cardiac investigations.     

Maxillary length in euploid and aneuploid fetuses

Purpose

To examine the maxillary length of euploid and aneuploid fetuses in the second and third trimester.

Methods

Retrospective study utilizing stored 2D images of second and third trimester fetal profiles obtained at the University of Tuebingen, Germany. The length of the maxilla was measured as a straight line between the anterior ventral and posterior ventral edges of the maxilla.

Results

The study population consisted of 347 euploid fetuses and 122, 36, 5, 8, and 4 fetuses with trisomy 21, 18, and 13, Turner syndrome, and triploidy. In the euploid and aneuploid group, mean gestational age was 22.3 and 22.7 weeks, respectively. The maxilla length in euploid fetuses was significantly dependent on gestational age and it was significantly shorter in fetuses with trisomy 21, 18, and 13, and triploidy but not in those with Turner syndrome. In 75.4 and 14.8%, and 11 fetuses with trisomy 21, the maxilla was below the mean, the 5th and 1st centile of the euploid population.

Conclusions

In fetuses with trisomy 21, 18, and 13 and triploidy, the maxilla is significantly shorter, but the difference is only settled, so that it is unlikely that the maxilla length will play a role in second and third screening for aneuploidy.

     

Fetal nasal bone and trisomy 21 in the second trimester

OBJECTIVES: To assess the feasibility of measuring nasal bone length in the second trimester of pregnancy and to confirm if fetal nasal bone absence or hypoplasia is a marker for Down syndrome. METHODS: Fetal nasal bone assessment was performed in 439 consecutive singleton pregnancies at high risk of Down syndrome between 15 and 21 weeks. All ultrasound examinations were performed transabdominally by five skilled sonographers. If the nasal bone was present, its length was measured. The biparietal diameter: nasal bone length ratio (BPD/NBL) was also calculated. RESULTS: Nasal bone assessment was successfully achieved in all fetuses. The nasal bone was absent in 2(0.47%) of the 417 unaffected fetuses and in 10(55.5%) of the 18 fetuses with trisomy 21. Of the 8 Down syndrome cases with a nasal bone present, 4 had nasal bone hypoplasia and 4 had a normal nasal bone. BPD/NBL was 9 or greater in 7 of the 8 fetuses affected by trisomy 21 with nasal bone present and in 86 (20.6%) of the 417 normal fetuses; it was 10 or greater in 5 of the 8 (62.5%) fetuses affected by trisomy 21 and in 41 of the 417 (9.8%) euploid fetuses. CONCLUSIONS: Nasal bone absence is a marker for Down syndrome in the second trimester of pregnancy. Inclusion of nasal bone length into the second-trimester screening protocol could potentially obviate the false-negative cases from other screening tests. The measurement of nasal bone length in the second trimester seems to provide additional benefits beyond the assessment of the presence or absence of the nasal bone.     

Amniotic fluid cathepsin-G in pregnancies complicated by the preterm prelabor rupture of membranes

Objective: The aim of this study was to evaluate the amniotic fluid cathepsin-G concentrations in women with preterm prelabor rupture of membranes (PPROM) based on the presence of the microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI).

Methods: A total of 154 women with singleton pregnancies complicated by PPROM were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid cathepsin-G concentrations were assessed by ELISA. MIAC was determined using a non-cultivation approach. IAI was defined as an amniotic fluid bedside interleukin-6 concentration?≥?745?pg/mL.

Results: Women with MIAC had higher amniotic fluid cathepsin-G concentrations than women without MIAC (with MIAC: median 82.7?ng/mL, versus without MIAC: median 64.7?ng/mL; p?=?0.0003). Women with IAI had higher amniotic fluid cathepsin-G concentrations than women without this complication (with IAI: median 103.0?ng/mL, versus without IAI: median 66.2?ng/mL; p?p?Conclusions: The presence of either microbial-associated or sterile IAI was associated with increased amniotic fluid cathepsin-G concentrations in pregnancies complicated by PPROM. Amniotic fluid cathepsin-G appears to be a potential marker of IAI.     

Amniotic fluid clusterin in pregnancies complicated by the preterm prelabor rupture of membranes

Objective: The aim of this study was to evaluate clusterin concentrations in amniotic fluid in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) with respect to the presence of the microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation (IAI) and microbial-associated IAI.

Methods: One hundred thirty-six women with singleton pregnancies complicated by PPROM were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid clusterin concentrations were assessed by enzyme-linked immunosorbent assay. MIAC was determined by a non-cultivation approach. IAI was defined as an amniotic fluid bedside interleukin-6 concentration?≥745?pg/mL. Microbial-associated IAI was characterized as the presence of both MIAC and IAI.

Result: Women with MIAC, IAI and microbial-associated IAI had lower amniotic fluid clusterin concentrations than women without these complications (with MIAC: median 1314?ng/mL versus without MIAC: median 1633?ng/mL, p?=?0.003; with IAI: median 1281?ng/mL versus without IAI: median 1575?ng/mL, p?=?0.04; with microbial associated-IAI: median 1220?ng/mL versus without microbial-associated IAI: median 1575?pg/mL; p?=?0.008). A week negative correlation between amniotic fluid clusterin concentrations and gestational age at sampling was revealed (rho=??0.30; p?=?0.0005).

Conclusions: The presence of MIAC, IAI and microbial-associated IAI was characterized by lower amniotic fluid clusterin concentrations in pregnancies complicated by PPROM.     

Altered amniotic fluid leptin levels in twin–twin transfusion syndrome with concurrent placental insufficiency

Objective: To measure amniotic fluid leptin levels in fetuses with twin–twin transfusion syndrome (TTTS) with and without placental insufficiency (PI) and determine its usefulness as a biomarker of PI.

Study design: A retrospective case control study of TTTS stage III patients from 2009 to 2011 was conducted. Cases were pregnancies with PI (TTTS-PI, n?=?18) matched by stage, gestational age, and degree of cardiomyopathy to controls without PI (TTTS, n?=?26). PI was strictly defined using biometric parameters. Amniotic fluid from recipient twins (RT) was taken during second trimester fetoscopic laser therapy. Leptin concentrations were determined and compared to growth parameters and birth weight.

Results: RT-adjusted leptin was 66% higher in TTTS-PI (p?=?0.016) compared to TTTS controls. Cases had significantly higher growth discordance (p?=?0.004) and lower RT birth weight (p?=?0.041) compared to controls. Significantly higher adjusted leptin levels were observed at birth in the TTTS-PI group when comparing those with SGA donor twins to those of normal weight (p?=?0.016).

Conclusion: These data suggest a role for leptin in pregnancies complicated by TTTS with placental insufficiency. However, further studies are needed to define its mechanism and potential role as a biomarker in amniotic fluid for placental pathophysiology.     

Quantitative evaluation of collagen type VI and SOD gene expression in the nuchal skin of human fetuses with trisomy 21

OBJECTIVE: To investigate the involvement of the genes encoding for COL6A1, COLA2 and super-oxide dismutase (SOD) in the mechanism for the retention of subcutaneous fluid in fetuses with trisomy 21. METHODS: During a 7-month period (November 2004-May 2005), human fetal skin from the nuchal region was obtained from euploid fetuses and from fetuses with trisomy 21 following abortions and terminations of pregnancy. Cell cultures were performed from nuchal skin. Quantification of COL6A1, COL6A2, COL6A3 and SOD mRNAs were performed using real-time quantitative RT-PCR. RESULTS: Twelve fetuses were studied between 13-15 and 19-20 weeks of gestation including 7 cases of trisomy 21. A significant overexpression of genes of interest was demonstrated in trisomy 21 fetuses when compared with euploid fetuses, in the first and in the second trimester of pregnancy (p < 0.0001). CONCLUSION: This study demonstrates a homogeneous overexpression of the genes encoding for alpha1 and alpha2 chains of Collagen type VI, and SOD in nuchal skin of human trisomy 21 fetuses. Persistence of this overexpression in the second trimester of pregnancy, despite the absence of an enlarged nuchal translucency (NT), may characterize some compensatory mechanisms.