Fetal cells in maternal blood of pregnancies with severe fetal growth restriction

The aim of this study was to examine whether, in pregnancies with severe early onset fetal growth restriction, the number of fetal erythroblasts in maternal blood is increased. The percentage of fetal erythroblasts in maternal blood, enriched by triple density gradient centrifugation and anti-CD71 magnetic cell sorting, was determined in 10 singleton pregnancies with severe intrauterine growth restriction in which there was Doppler ultrasound evidence of impaired placental perfusion. The values were compared to those of 10 normal pregnancies at the same gestational range of 22-26 weeks. In the growth restricted pregnancies the median number of fetal erythroblasts per 100 nucleated cells in maternal blood enriched for fetal cells was significantly higher than the median value in the control pregnancies (8.5% compared with 1%; P < 0.001). These data suggest that impaired uteroplacental perfusion and severe fetal growth restriction may be associated with placental damage leading to increased feto-maternal cell traffic. Alternatively the rate of transfer of fetal cells into the maternal circulation is not altered but in growth restriction the proportion of fetal erythroblasts in fetal blood is increased.     

Distribution of fetal erythroblasts enriched from maternal blood in multifetal pregnancies

BACKGROUND: The aim of this study was to establish the frequency of fetal cells in the maternal blood of multifetal pregnancies and compare this figure with singleton pregnancies. METHODS: We obtained maternal blood from 31 pregnancies with 2-6 fetuses at 11-16 weeks gestation and from 50 normal singleton controls (11-14 weeks gestation). Fetal erythroblasts were isolated from maternal blood using triple density gradient separation and anti-CD71 magnetic cell-sorting techniques. The enriched erythroblasts were stained with Kleihauer-Giemsa and with fluorescent antibodies for the zeta (zeta), epsilon (epsilon) and gamma (gamma) globin chains. The percentage of fetal cells positive for each stain was calculated. Fluorescence in-situ hybridization (FISH) for X and Y chromosomes was also performed. RESULTS: The percentage of erythroblasts enriched from maternal blood that stained positive for zeta, epsilon and gamma globin chains and with Kleihauer-Giemsa was significantly higher in the multifetal compared with singleton pregnancies. The median enriched percentage of positively stained erythroblasts was about three times higher in the twin than in singleton pregnancies (P < 0.0001), nearly twice as high in the triplet than in twin pregnancies (P < 0.01) and five times higher in the triplet than singleton pregnancies (P < 0.0001). FISH for Y chromosome confirmed the increase in fetal cell proportion in the multifetal pregnancies. CONCLUSIONS: These findings suggest that there is an increase in the physiological feto-maternal cell trafficking in multifetal pregnancies compared with singleton pregnancies, which is likely to be due to the increased placental surface area and vasculature.     

The role of insulin-like growth factor binding protein-1 phosphoisoforms in pregnancies with impaired placental function identified by doppler ultrasound.

This study was performed to investigate the hypothesis that insulin-like growth factor binding protein-1 (IGFBP-1) is involved in the pathogenesis of trophoblast invasion and impaired placentation in human pregnancy. The role of total and non-phosphorylated IGFBP-1 in women with fetal growth restriction and in high risk pregnancies identified by uterine artery Doppler ultrasound screening was examined. This was a prospective study of women booked for antenatal care having second trimester anomaly scans and Doppler screening between 22-26 weeks gestation. Women were divided into three groups and compared: normal uterine artery Doppler and normal fetal growth (control group, n = 10); abnormal Doppler and normal fetal growth [bilateral uterine artery notches (BN; n = 16); abnormal Doppler and intrauterine growth restriction (IUGR; n = 8)]. Maternal serum was collected, stored and assayed simultaneously for total and non-phosphorylated IGFBP-1. There was elevated total and non-phosphorylated IGFBP-1 (mean 44.99 +/- 12.19 and 29.61 +/- 10.38 microg/l respectively) in the IUGR group compared with controls (mean 17.96 +/- 3.24 and 12.18 +/- 1.55 microg/l, P < 0.05). This finding suggests that the various IGFBP-1 isoforms, the degree of phosphorylation and the ratios of these different forms locally may be important during trophoblast invasion and may be implicated in clinical manifestations of impaired placentation later in the second trimester.     

11Beta-hydroxysteroid dehydrogenase type 2 in human pregnancy and reduced expression in intrauterine growth restriction

The type 2 isoform of 11beta-hydroxysteroid dehydrogenase (11beta- HSD2), which inactivates cortisol (F) to cortisone (E), has been suggested to play a role in the ontogeny of the fetal pituitary-adrenal axis and also protect the developing fetus from the deleterious effects of circulating maternal glucocorticoids. The abundance of 11beta-HSD2 in the placenta and other fetal tissues was inferred from the F/E ratio in 17 term deliveries in both umbilical arterial (1.73 +/- 0.24, mean +/- SE) and umbilical venous blood (1.16 +/- 0.14) compared with adult peripheral venous blood (7.76 +/- 0.57, n = 70). Using sensitive assays for 11beta-HSD2 and an in-house human 11beta-HSD2 antibody, the expression and activity of this enzyme in fresh frozen human placenta increased progressively from first (8-12 weeks, n = 16) and second (13- 20 weeks, n = 9) to third trimester (term) pregnancies (39-40 weeks, n = 50). Placental 11beta-HSD2 activity was significantly reduced in deliveries complicated by intrauterine growth restriction (IUGR) [25-36 weeks, n = 12, activity 380 pmol/mg/h median (225-671; 95% confidence interval)], compared with the term deliveries [888 (725-1362)] and with appropriately grown pre-term deliveries [27-36 weeks, n = 14, activity 810 (585-1269)], P < 0.05. In human pregnancy placental 11beta-HSD2 activity increases markedly in the third trimester of pregnancy at a time when maternal circulating levels of glucocorticoid are rising. The finding of attenuated placental 11beta-HSD2 activity in IUGR suggests that glucocorticoids may, in part, contribute to impaired fetal growth and that this is closely controlled in normal gestation through placental 11beta-HSD2 expression.      

Vascular endothelial growth factor (VEGF) and discrimination between abnormal intrauterine and ectopic pregnancy

BACKGROUND: This study evaluated serum vascular endothelial growth factor (VEGF) levels in women with abnormal intrauterine and ectopic pregnancies (EP) at 6 weeks gestation. METHODS: We conducted a prospective case-control study comparing serum VEGF concentrations among 84 women with abnormal intrauterine and EP matched for gestational age (42 women in each group). We analysed whether serum VEGF levels >200 pg/ml would discriminate between abnormal intrauterine pregnancies and EP at 6 weeks gestation, and we calculated sensitivity, specificity and positive predictive values. RESULTS: Serum VEGF concentrations did not show statistically significant differences between women with abnormal intrauterine pregnancies (median, 198.5 pg/ml; range, 0-701.6) and EP (median, 211.2 pg/ml; range 0-628.8). When threshold concentrations of a serum VEGF level >200 pg/ml were used, abnormal intrauterine pregnancy could be distinguished from EP with a sensitivity of 56%, a specificity of 51%, and a positive predictive value of 53%. CONCLUSIONS: VEGF does not discriminate ectopic from abnormal intrauterine pregnancies at 6 weeks gestation, and thus should not be used in clinical management.     

Early prediction of severe twin-to-twin transfusion syndrome

This extended series of 303 monochorionic twin pregnancies examined at 10-14 weeks gestation explores the possible association of increased fetal nuchal translucency thickness (NT) in the early prediction of severe twin-to-twin transfusion syndrome (TTS). Of 303 pregnancies, there were 16 in which at least one fetus was structurally or chromosomally abnormal and in the remaining 287 ongoing pregnancies there were 43 (15%) which developed severe TTS. The median fetal NT was 1.0 multiples of the median (MOM) and NT was >95th centile in 47 (8.2%) fetuses and in at least one fetus in 37 (12.9%) pregnancies. The prevalence of increased NT in the pregnancies that developed TTS [17.4% (n = 15) of fetuses and 28% (n = 12) of pregnancies] was significantly higher than in the non-TTS group [6.6% (n = 32) and 10.2% (n = 25) respectively; Z: = -3.4, P: < 0.001 and Z: = 3.2, P: < 0.001 respectively], likelihood ratio of increased fetal NT for prediction of TTS = 3.5 [95% confidence interval (CI) 1.9-6.2]. In 153 of the pregnancies, an ultrasound examination was also performed at 15-17 weeks gestation and intertwin membrane folding was seen in 49 (32%) cases; 21 of these (43%) subsequently developed TTS compared to two (1.9%) of the 104 pregnancies without membrane folding (Z: = 6.6, P: < 0.001), likelihood ratio of membrane folding for prediction of TTS = 4.2 (95% CI 3.0-6.0).     

Characterization of first trimester fetal erythroblasts for non-invasive prenatal diagnosis

Isolating fetal erythroblasts from first trimester maternal blood offers a promising non-invasive alternative for prenatal diagnosis. The aim of this study was to characterize the biological properties of first trimester primitive erythroblasts to facilitate their enrichment from first trimester maternal blood. Primitive erythroblasts were the predominant cell type until 12 weeks gestation, after which time their numbers declined steeply; 100% were epsilon-globin-positive versus <0.06% definitive erythroblasts. Buoyant densities of first trimester fetal erythroblasts ranged from 1.077 to 1.130 g/ml, and optimal recoveries were obtained with Percoll 1118. Although primitive erythroblasts carried a negative surface charge and were resistant to NH(4)Cl lysis, these properties had only a limited role in fetal cell enrichment. Immunophenotyping showed that primitive, like definitive, erythroblasts were GPA+, CD47+, CD45- and CD35-, whereas CD71 expression was weak/undetectable on primitive erythroblasts but strongly positive on 100% of definitive erythroblasts; primitive erythroblasts were also CD36- whereas definitive erythroblasts were CD36+. We therefore used CD45/GPA selection of Percoll 1118-separated cells to demonstrate successful enrichment of male epsilon-globin-positive fetal erythroblasts from model mixtures, and as proof of principle from some first trimester maternal blood samples. Fetal cell enrichment protocols based on first trimester epsilon-globin-positive primitive erythroblasts may allow reliable enrichment of fetal cells from maternal blood for early non-invasive prenatal diagnosis of genetic disorders.     

Relationship between maternal serum vascular endothelial growth factor concentration in early pregnancy and fetal and placental growth.

Vascular endothelial growth factor (VEGF) has important effects on endothelial cells increasing cell proliferation, permeability and nitric oxide production; concentrations of VEGF in the maternal serum increase during the first 10 weeks of pregnancy. In this study, the relationship of maternal serum VEGF with maternal health during pregnancy and with fetal and placental size at mid-pregnancy and at term was investigated. Serum was obtained from 539 Caucasian women with singleton pregnancies between 8 and 20 weeks of pregnancy (mean 14 weeks). Total serum VEGF concentrations were measured by direct competitive radioimmunoassay. Fetal size and placental volume were measured by ultrasound between 16 and 20 weeks gestation. Birthweight, placental weight and anthropometric measurements of the baby were obtained after delivery. Serum VEGF concentrations were found to be higher in women with a lower weight before pregnancy (P = 0.01) and in those carrying a female fetus (P = 0.002). VEGF concentrations were positively correlated with placental volume (r = 0.17, P = 0.0001) but not with fetal size between 16 and 20 weeks gestation. Serum VEGF concentrations were positively correlated with both birthweight (r = 0.10, P = 0.02) and placental weight at delivery (r = 0.13, P = 0.003). The data presented support the view that VEGF may be one of the factors involved in mediating the maternal cardiovascular adaptation to pregnancy.     

Abnormal placental cord insertion may induce intrauterine growth restriction in IVF-twin pregnancies

BACKGROUND: This study determined whether twins conceived through assisted reproduction technology (ART) have an increased risk of perinatal complications compared with natural twin pregnancies and investigated potential associated major risk factors. METHODS: This retrospective study consisted of 199 twins born between 1994 and 2003. There were four groups according to conception modalities: 97 twins after spontaneous pregnancy, 24 after induced ovulation, 28 after intrauterine insemination (IUI) and 50 after IVF with embryo transfer. Analysis included preterm birth, Caesarean delivery, weight discordance, intrauterine growth restriction (IUGR), low-birth-weight, Apgar score, chorionicity, gross placental pathology and placental umbilical cord insertion (UCI) site. RESULTS: A significant difference was found in IUGR between the IVF group (7.0%) and spontaneous pregnancy group (14.9%). When maternal age was >30 years there was a 2.86-fold increase in the risk of IUGR. There was a 3.69-fold increased risk of IUGR in the presence of abnormal UCI (odds ratio 3.69, 95% CI 1.62-8.42) and a 2.18-fold increased risk of abnormal UCI in monochorionic twins when compared with dichorionic twins (odds ratio 2.18, 95% CI 1.30-3.66). CONCLUSION: Twins conceived through ART are not at an increased risk of perinatal complications. A relationship has been found between abnormal UCI and IUGR.     

Cytokine imbalance in pregnancies with fetal chromosomal abnormalities

BACKGROUND: The aim of the present study is to investigate the levels of some of the cytokines which may be involved in the mechanisms leading to the impairment of placental perfusion and to the onset of uterine contractions in pregnancies with fetal genetic abnormalities compared with controls. METHODS: The amniotic fluid and maternal plasma levels of interleukin-6, interleukin-8 and tumour necrosis factor-beta in patients with fetal chromosomal abnormalities were measured, as well as in euploid pregnancies in the seventh week of gestation. RESULTS: An increase of interleukin-6 (P = 0.034) and a decrease of interleukin-8 (P < or =0.0001) in amniotic fluid, and a decrease of interleukin-6 in the maternal plasma (P = 0.026) was shown in pregnancies with fetal chromosomal abnormalities. A positive correlation was observed between amniotic interleukin-8 and serum interleukin-6 in the presence of fetal aneuploidy (P < 0.006). CONCLUSION: Further investigations of cytokine imbalance in pregnancies with poor outcome as a consequence of genetic disorders rather than infection is warranted.     

Homeobox gene ESX1L expression is decreased in human pre-term idiopathic fetal growth restriction

Fetal growth restriction (FGR) is a clinically significant pregnancy disorder in which the fetus fails to achieve its full growth potential in utero. This study involved idiopathic FGR, which is frequently associated with placental dysfunction. Here, we investigated mRNA levels of the human placental homeobox gene ESX1L in pre-term and term idiopathic FGR pregnancies compared with gestation-matched controls. Real-time PCR quantitation showed ESX1L levels in control placentae decreased between pre-term and term [0.7 +/- 0.20 (27-35 weeks, n = 13) versus 0.2 +/- 0.06 (36-41 weeks, n = 12), t-test, P < 0.005]. ESX1L levels in FGR-affected placentae were significantly lower than in gestation-matched controls, and there was no significant change between pre-term FGR and term FGR [0.32 +/- 0.04 (27-36 weeks, n = 11) versus 0.31 +/- 0.02 (36-41 weeks, n = 14), t-test, P = 0.82]. Multiple linear regression analysis revealed a rapid decline in ESX1L expression in control placentae [0.075-fold of the calibrator for each week of gestation (95% CI = -0.105 to -0.045, P < 0.0005)]. In FGR-affected placentae, ESX1L levels were lower than in gestation-matched controls, and the decline in ESX1L levels with gestation was not significant [0.001-fold of the calibrator for each week of gestation (95% CI = -0.030 to 0.010, P < 0.3]. The linear relationship between ESX1L mRNA levels in FGR-affected placentae and gestation-matched controls during gestation was significantly different (likelihood ratio test for interaction, P = 0.0005). Our findings were consistent with a potential role for the ESX1L gene within the growth control mechanism of the fetus, through its effect on placental function.     

The placenta in pre-eclampsia and intrauterine growth restriction

Placental examination in pregnancies with complications such as pre-eclampsia/toxaemia of pregnancy (PET) or intrauterine growth restriction (IUGR) can provide insight into specific diagnoses, recurrence risk and chronicity. Placental findings have clinical significance as they can identify the aetiology of the IUGR (as in inborn errors of metabolism) and predict recurrence (as in maternal floor infarcts). Evaluation of obstetric pathology in such pregnancies should be an integral part of clinical care. This review will highlight the placental findings in IUGR and PET.     

Male sex bias in placental dysfunction

Several reports suggest a male fetal preponderance in a variety of complications of pregnancy attributable to severe placental dysfunction (SPD). However, the underlying mechanisms remain unknown. Our primary objective was to explore the relationship between fetal sex and the spectrum of conditions implicated in abnormal placentation. We identified singleton pregnancies with a fetus delivered between 20?+?0 and 32?+?6 weeks of gestation with one or more pregnancy complications attributed to SPD (severe pre-eclampsia, intra-uterine fetal death, intra-uterine growth restriction, abnormal Doppler studies, abruption) at a single institution between 1999 and 2007. Pedigrees of index cases were created to define the relationship between fetal sex and the risk of SPD. We identified 132 index cases, 97/132 (73%) were male. Eighty-four index cases had a total of 133 sibs, of which 37/133 (28%) were affected with SPD (22 male, 15 female). A male sex preponderance persisted across all manifestations of PD in index cases with sibs. In families with the absence of maternal chronic hypertension (cHTN; n?=?70), the index case was 5.9 (95% CI 2.28-16.15; P?<0.001) times more likely to be male and most (12/14) affected sibs of male index cases were male, while female index cases had no affected sibs. Our results confirm a male fetal sex preponderance in SPD. In a subgroup analysis of families without cHTN, a significant male bias was found to extend to sibs of index cases. This suggests a potential genetic mechanism predisposing the male fetus to abnormal placental development.     

Early transvaginal embryo aspiration: a safer method for selective reduction in high order multiple gestations.

Assisted reproduction technologies and ovulation induction for treatment of infertility continue to cause high order multiple gestations. Increased perinatal morbidity and mortality, as well as maternal morbidity, may complicate these pregnancies. Selective fetal reduction, an acceptable therapeutic approach in these cases, is usually performed at or after the ninth week of gestation, with KCl injected in the vicinity of the fetal heart, and is associated with a total pregnancy loss rate of 11.7%. We report our experience with 90 women who underwent early (mean 7.5 weeks gestation, range 7. 0-8.0 weeks) transvaginal selective embryo aspiration. The mean number of viable embryos before and after reduction was 3.5 and 2.1 respectively. Six (6.7%) pregnancies were lost before 24 gestational weeks. One miscarriage occurred at the tenth gestational week. The other five pregnancies were aborted at 17.3-21.6 weeks gestation. Additional interventions were performed in three of these pregnancies: genetic amniocentesis in two cases and cervical suture in one case. In the subset of 39 patients with>/=4 embryos, only one (2.6%) pregnancy loss was recorded. This loss rate is significantly lower (P < 0.05) than the 15.3% loss rate in patients with >/=4 fetuses calculated from other work. Four (4.4%) other pregnancies were complicated by premature delivery (25-28 weeks gestation). Mean gestational age of delivered pregnancies in our series was 35.7 weeks. In conclusion, early transvaginal embryo aspiration is a simple and relatively safe method for multiple pregnancy reduction. The overall pregnancy loss rate associated with early embryo aspiration is similar to that of procedures performed at later gestational age, but is significantly lower when the initial number of embryos is four or greater.     

Correlation between first trimester fetal bone length and maternal serum pregnancy-associated plasma protein-A (PAPP-A)

BACKGROUND: Pregnancy-associated plasma protein-A (PAPP-A) is produced by the embryo and placenta during pregnancy, and its maternal serum concentrations are related to subsequent fetal growth. Evidence from animal models and in vitro experiments suggests that PAPP-A is particularly involved in the regulation of bone development. The aim of this study was to assess the correlation between late first trimester fetal bone length and maternal serum levels of PAPP-A. METHODS: In a cross-sectional observational study, ultrasound measurements of fetal long bones and fluorimetric immunoassays for maternal serum PAPP-A were performed in 514 singleton pregnancies at 10-14 weeks of gestation. RESULTS: There were 501 uncomplicated pregnancies. There were significant correlations between PAPP-A values and length of humerus, femur and tibia [r values 0.12 (P = 0.01), 0.11 (P = 0.01) and 0.10 (P = 0.03), respectively]. The association with the length of ulna and foot did not reach statistical significance (r values 0.08 and -0.03, respectively). CONCLUSIONS: Maternal serum PAPP-A levels at 10-14 weeks of gestation are significantly associated with the length of fetal long bones such as humerus, femur and tibia. This provides further evidence that PAPP-A may be involved in the regulation of bone development.     

Placental leptin in normal, diabetic and fetal growth-retarded pregnancies

Leptin expression in third trimester placenta (p) and leptin concentrations in umbilical cord blood (cb) were investigated in normal pregnancies [n = 10 (p), 31 (cb)] and abnormal pregnancies complicated with (i) maternal insulin-dependent diabetes [IDDM: n = 3 (p), 13 (cb)], (ii) gestational diabetes [GD: n = 2 (p), 10 (cb)] and (iii) fetal growth retardation [FGR: n = 5 (p), 5 (cb)]. By in-situ hybridization and immunohistochemistry, placental leptin mRNA and protein were co-localized to the syncytiotrophoblast and villous vascular endothelial cells. Leptin receptor was immunolocalized to the syncytiotrophoblast. Relative to controls, the FGR group was characterized by low concentrations of placental and cord blood leptin. In a twin pregnancy, the normal-sized infant exhibited more placental and cord blood leptin than its growth-retarded twin. In contrast, both diabetic groups exhibited high concentrations of placental leptin mRNA and protein. The IDDM group exhibited the highest concentrations of leptin in cord blood. No change was observed in the expression of the leptin receptor in either the growth-retarded or diabetic pregnancies. In conclusion, the localization of placental leptin suggests that it may be released into both maternal and fetal blood. Furthermore, in fetal growth-retarded and diabetic pregnancies, the changes in leptin expression in the placenta and in leptin concentrations in umbilical cord blood appear to be related.     

Preterm delivery and growth restriction in multifetal pregnancies reduced to twins

Gestation at delivery, birthweight and pregnancy outcome of surviving fetuses from 127 multifetal pregnancies undergoing embryo reduction to twins were compared to 354 chromosomally normal non-reduced dichorionic twin pregnancies. First-trimester embryo reduction was carried out by intracardiac injection of KCl. In 16 (12.6%) of the 127 multifetal pregnancies reduced to twins, there was miscarriage of both fetuses before 24 weeks of gestation. The median interval between reduction and fetal loss was 5 weeks (range 1-12). In livebirths, the median gestation at delivery was 36 weeks (range 24-41) and the median difference in birthweight from the appropriate mean was -0.94 SD (range -3.89-1.73 SD). Both fetal loss before 24 weeks and the interval between embryo reduction and delivery were significantly associated with the gestation at reduction (r = 0.40, P < 0.001 and r = -0.57, P < 0.001 respectively). In the pregnancies reduced to twins compared to the non-reduced twins, the percentage of miscarriages was higher (12.6 compared to 2.5%; chi 2 = 19.2, P < 0.001), the median gestation at delivery was lower (36 compared to 37 weeks; t = -1.74, P < 0.05), and the median birthweight deficit was greater (-0.94 compared to -0.65 SD: t = -4.1, P < 0.001).      

Risk factors associated with fetal losses in treated antiphospholipid syndrome pregnancies: a multivariate analysis

PROBLEM: Pregnancies in women with antiphospholipid syndrome (APS) are associated with obstetric complications despite treatment. The present study analyzes risk factors and evaluates fetal outcome in a large sample of treated APS pregnancies. METHOD OF STUDY: Seventy-seven pregnancies in 56 women were included. Twelve selected variables potentially related to the outcome of treated pregnancies were analyzed in a multivariate logistic regression model. RESULTS: Treated women delivered 65 live infants at 24-41 weeks gestation (mean 36.7+/-0.5) but two neonatal deaths occurred. There were seven first-trimester miscarriages (9%) and five intrauterine fetal demises (6.5%). Thus, the probability of having a live baby under treatment was 82% (95% CI 71.3-89.6%), a figure significantly greater (P <0.001) than that observed before therapy (25.7%; 95% CI 18.7-33.7%). Variables related with fetal outcome in the multivariate model were: preconceptional use of aspirin and abnormal umbilical artery Doppler velocimetry at 23-26 weeks gestation. CONCLUSIONS: The present report shows that in treated APS pregnancies: i) aspirin treatment started preconceptionally is an independent and significant prognostic factor associated with favorable fetal outcome; and ii) abnormal velocity waveforms in the umbilical artery predict adverse outcome of pregnancy.     

Fetal growth according to different reference ranges in twin pregnancies with placental insufficiency

The aim of this study was to compare different fetal growth curves in twin pregnancies with severe placental insufficiency. A retrospective cross-sectional analysis of 47 twin pregnancies with absent or reverse end diastolic flow in the umbilical artery of one fetus was performed. Pregnancies with major fetal abnormalities, twin-twin transfusion or three or more fetuses were not included. The estimated fetal weight zeta-scores were calculated for both fetuses (abnormal Doppler and co-twin) according to the following criteria: Hadlock, Liao and Araújo. The abdominal circumference zeta-scores were calculated according to Hadlock, Liao, Araújo, Ong and Stirrup. The mean estimates of the zeta-score values were calculated using generalized estimating equation regression analysis.The mean gestational age at inclusion was 27.4±4.7 weeks. The fetal sex and the interaction Doppler findings × criteria correlated significantly with the zeta-score values (p<0.001 for both variables). The estimated fetal weight mean zeta-scores (standard error) according to each criteria were as follows: Hadlock - abnormal Doppler: -2.98 (0.18), co-twin: -1.16 (0.15); Liao - abnormal Doppler: -2.89 (0.24), co-twin: -0.58 (0.19); and Araújo - abnormal Doppler: -3.05 (0.29), co-twin: -0.75 (0.18). Values for abdominal circumference were as follows: Hadlock - abnormal Doppler: -3.14 (0.26), co-twin: -1.13 (0.19); Liao - abnormal Doppler: -2.63 (0.27), co-twin: -0.42 (0.19); Araújo - abnormal Doppler: -2.44 (0.22), co-twin: -0.71 (0.14); Ong - abnormal Doppler: -3.36 (0.34), co-twin: -1.48 (0.23); and Stirrup AD -- -2.36 (0.14), co-twin: -1.18 (0.10).Sex- and plurality-specific charts should be used in the evaluation of fetal growth in twin pregnancies with placental insufficiency.     

Second-trimester maternal urine human chorionic gonadotrophin beta-core fragment concentrations in Asian pregnancies with fetal chromosomal abnormalities.

The aim of this study was to investigate the second trimester concentrations of maternal urine human chorionic gonadotrophin beta-core fragment (HCGbetacf) in Asian pregnanci2es with fetal chromosomal abnormalities. HCGbetacf concentrations were analysed from 34 urine samples in chromosomally abnormal pregnancies, including 28 cases of Down's syndrome, one case of trisomy 18, and five cases of other chromosomal abnormalities (one mosaic deletion and four translocations), and in a cohort of 268 normal pregnancies receiving second trimester amniocentesis. Results were normalized to urine creatinine (Cr) concentration and converted to the multiple of the median (MOM) concentration for the appropriate gestation. The median HCGbetacf MOM concentrations of Down's syndrome pregnancies (12.89) was significantly higher than that of normal pregnancies (1. 06) (P < 0.00001). Wide variations of HCGbetacf concentrations were observed in other chromosomally abnormal pregnancies. There were 18 of 28 (64%) Down's syndrome cases but one of five (20%) other chromosomally abnormal cases with HCGbetacf concentrations above the 95th centile of the control values (8.22 MOM cut-off). These findings suggest that HCGbetacf could be a potential marker in urine screening for fetal Down's syndrome in Asians.