Differential expression of cord blood neurotrophins in gestational diabetes: the impact of fetal growth abnormalities

Objective: Gestational diabetes mellitus (GDM) may induce fetal macrosomia or growth restriction and is associated with later offspring neurodevelopmental disorders. We aimed to determine whether neurotrophins brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-4 (NT-4) are differentially expressed in cord blood samples at birth in large-for-gestational-age (LGA), intrauterine-growth-restricted (IUGR) and appropriate-for-gestational-age (AGA) offspring of diabetic mothers, as compared to AGA controls from non-diabetic mothers.

Methods: BDNF, NGF and NT-4 concentrations were prospectively determined in 80?cord blood samples from LGA (n?=?15), IUGR (n?=?12) and AGA (n?=?33) diabetic, as well as from AGA normal (controls, n?=?20) singleton full-term pregnancies.

Results: Fetal BDNF concentrations considerably decreased in GDM, as compared with normal pregnancies [(b?=??2.836, 95%CI ?5.067 to (?0.604), p?=?0.013)] and were higher in females (b?=?2.298, 95%CI 0.357–4.238, p?=?0.021). Cord blood NGF concentrations were lower in IUGR than AGA infants (p?=?0.038).

Conclusions: BDNF is down-regulated in the fetus exposed to GDM, independently of the fetal growth pattern, probably representing a candidate mechanism underlying the association between maternal diabetes and later psychopathology. IUGR fetuses born to diabetic mothers present with NGF deficiency, which may contribute to their long-term neurodevelopmental sequelae. Gender-dependent differences in fetal BDNF may partly explain the higher prevalence of adverse neurodevelopmental outcomes following brain insults in male infants.     

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.     

Delivery prediction in pregnant women with spontaneous preterm birth using fetal adrenal gland biometry

Objective: To assess the prediction of delivery within 7 days in pregnant women who showed symptoms of spontaneous preterm birth (PB) by means of fetal adrenal gland biometry and to compare these predictions with the cervical length (CL) measurement.

Methods: We performed a prospective cross-sectional study with 53 pregnant women between 24 and 36 weeks of gestation. An ultrasound exam was performed for each participant to obtain the CL measurement (transvaginal route) and fetal adrenal gland biometry on day 1 of their hospital admission because of symptoms of spontaneous PB. The main outcome measure was the time between the ultrasound exam and delivery, which was classified into two groups: delivery ≤7 days and delivery >7 days. A receiver operating characteristics (ROC) curve was performed to define the cutoffs for sensitivity and specificity.

Results: The prevalence of delivery within 7 days was 35.8%, which showed a statistically significant difference from the depth of the central zone of the fetal adrenal gland (p = 0.036). The cutoff for the depth of the central zone of the fetal adrenal gland was 7.2?mm (sensitivity 66.7%, specificity 61.8% and accuracy 63.5%). These values were not significantly different than the cutoffs for cervical length measurement: 20?mm (p = 0.267) and 9?mm (p = 0.118).

Conclusion: The biometry for the central zone of the fetal adrenal gland predicted delivery within 7 days in pregnant women with spontaneous PB and had a predictive accuracy similar to that of CL measurement.     

Fetal adrenal gland volume and cortisol/dehydroepiandrosterone sulfate ratio in inflammation-associated preterm birth

OBJECTIVE: Fetal adaptation to stress is regulated in part by the pituitary-adrenocortical system. The stress hormones dehydroepiandrosterone sulfate (DHEAS) and cortisol have opposing effects: cortisol suppresses while DHEAS enhances immune functions. We sought to estimate the impact of intraamniotic inflammation on fetal adrenal gland volume and cortisol-to-dehydroepiandrosterone sulfate ratio (fetal stress ratio) in pregnancies complicated by preterm birth. METHODS: Fifty-one consecutive singleton fetuses of mothers who had an indicated amniocentesis to rule out infection were analyzed. Intraamniotic inflammation was assessed by proteomic profiling of amniotic fluid for the biomarkers of the Mass Restricted score. The Mass Restricted score ranges from 0 (biomarkers absent) to 4 (all biomarkers present), with Mass Restricted scores of 3 or 4 indicating severe intraamniotic inflammation. Fetal adrenal gland volume was assessed by three-dimensional ultrasonography and corrected for estimated fetal weight. Interleukin-6 (IL-6), cortisol, and DHEAS were measured by immunoassay. RESULTS: Women with intraamniotic inflammation delivered earlier (27.8+/-3.4 weeks, n=16, compared with 32.3+/-3.0 weeks, n=35, P<.001), and their fetuses had higher cord blood IL-6 (P=.011) and higher corrected adrenal gland volumes (P=.027). Cord blood IL-6 levels were in direct relationship with corrected adrenal volume (r=0.372, P=.019), fetal cortisol (r=0.428, P=.010), and DHEAS (r=0.521, P<.001). However, fetuses exposed to intraamniotic inflammation had an overall lower fetal stress ratio (P=.034). These results maintained after adjusting for gestational age, uterine contractions, and steroid exposure. CONCLUSION: Fetuses exposed to intraamniotic inflammation have higher adrenal gland volumes and lower cortisol-to-DHEAS ratios, suggesting that the fetal adrenocortical axis plays a role in the intrauterine adaptation to inflammation.     

Assessment of motoric and hemodynamic parameters in growth restricted fetuses – case study

Abstract

Objective: In order to more accurately assess fetal neurological status in five fetuses with severe intrauterine growth restriction (IUGR), combined assessment of their hemodynamics and motor activity was undertaken in this study.

Method: Hemodynamic changes in the placental and fetal cerebral vessels were evaluated using the umbilical artery resistance index (URI), and the middle cerebral artery resistance index (CRI). The blood flow redistribution towards the fetal brain in response to fetal hypoxia was detected by the C/U (cerebro – umbilical) ratio, expressed as CRI/URI.

Motoric parameters were assessed by new antenatal neurologic scoring test named Kurjak Antenatal Neurodevelopmental Test (KANET), based on evaluation of spontaneous motor activity using four-dimensional (4D) ultrasound.

Results: KANET has potential in recognizing pathologic and borderline behavior in IUGR fetuses with or without blood flow redistribution towards the fetal brain. Very low values of C/U ratio and abnormal KANET score have indicated adverse pregnancy outcome.

Conclusion: In some pregnancies complicated with IUGR, estimation of the risk of hypoxia versus prematurity can be extremely puzzling. Combined assessment of hemodynamic and motoric parameters in IUGR fetuses could allow construction of an algorithm, which would be helpful in the decision making process of pregnancy termination.     

Fetal adrenal gland volume and preterm birth: a prospective third-trimester screening evaluation

Objective: Given the importance of the fetal adrenal gland in producing hormones critical to labor, we sought to evaluate whether sonographic three-dimensional measurements of the adrenal gland are a useful screening tool for spontaneous preterm birth (SPTB).

Method: We prospectively screened 128 non-anomalous singletons from 24 to 36 weeks' gestation with volumetric measurements of the fetal adrenal gland at their indicated antenatal sonogram. Labor and delivery outcomes were assessed and compared with respect to adrenal volume.

Results: When corrected for estimated fetal weight, the 11 women (9%) who delivered following SPTB had smaller adrenals than those who did not, 0.33?cm³/kg compared with 0.57?cm³/kg, respectively (p?=?0.006). There was no difference in volumes between those who delivered by SPTB within 7 days or greater than 14 days from measurement (0.34?cm³/kg versus 0.33?cm³/kg, p?=?0.79). Among women at increased risk of SPTB, those with SPTB had smaller adrenals than those who did not: 0.32?cm³/kg versus 0.53?cm³/kg, p?=?0.06.

Conclusion: We found fetal adrenal glands significantly smaller for those delivering preterm. Given the prior literature and our asymptomatic population, our data support multiple pathways leading to SPTB.     

Fetal adrenal gland volume: a novel method to identify women at risk for impending preterm birth

OBJECTIVE: To investigate the risk of preterm birth (delivery at less than 37 weeks of gestation) by evaluating the fetal adrenal gland volume, hallmark of activation of the fetal hypothalamic-pituitary-adrenal axis, measured by 3-dimensional ultrasonography. METHODS: We performed 3-dimensional ultrasound examination of the fetal adrenal gland volume in 126 singleton fetuses, prospectively comparing those born to mothers with signs or symptoms of preterm labor (n=53) to control subjects (n=73). Multiplanar technique with rotational methods for measurement of fetal adrenal gland volume was performed by using Virtual Organ Computer-Aided Analysis (VOCAL) technology. RESULTS: The fetal adrenal gland volume was successfully examined in 86.5% of the cases. There was a direct relationship between the fetal adrenal gland volume and estimated fetal weight. A corrected adrenal gland volume of greater than 422 mm3/kg was best in predicting preterm birth within 5 days from the time of the measurement. The sensitivity, specificity, and positive and negative likelihood ratios were 92%, 99%, 93.5, and 0.08, respectively. Multiple logistic regression analysis showed that the corrected adrenal gland volume was the only significant independent predictor factor of preterm birth within 5 days of measurement. CONCLUSION: Corrected adrenal gland volume measurement may identify women at risk for impending preterm birth. This information can be generated noninvasively and in time for clinical decision making. LEVEL OF EVIDENCE: II.     

Plasma copeptin may not be a sensitive marker of perinatal stress in healthy full-term growth-restricted fetuses

Objective: Intrauterine-growth-restriction-(IUGR) is associated with chronic fetal stress, as well as a phase of enhanced fetal/early postnatal insulin sensitivity, followed by a later emergence of insulin resistance. We aimed to prospectively investigate concentrations of copeptin, a sensitive marker of stress and insulin resistance, in IUGR versus appropriate-for-gestational-age-(AGA) fetuses.

Methods: Cord blood copeptin concentrations were determined by ELISA in well-defined, non-distressed at birth, asymmetric IUGR (n?=?30) and AGA (n?=?20) full-term pregnancies. Doppler studies were indicative of placental insufficiency.

Results: Cord blood copeptin concentrations were similar in IUGR cases and AGA controls, after controlling for delivery mode. Copeptin concentrations were markedly elevated in vaginally delivered fetuses (p?=?0.001). No association was recorded between fetal copeptin concentrations and maternal age, parity, gestational age, or fetal gender.

Conclusions: Cord blood copeptin concentrations are probably not affected by IUGR at term, in the absence of fetal distress, possibly due to a balance between copeptin up-regulation by chronic fetal stress, on one hand, and copeptin down-regulation in the presence of increased insulin sensitivity, on the other hand; thus, copeptin may not be a sensitive marker of chronic perinatal stress in healthy asymmetric IUGR infants. Cord blood copeptin seems to primarily reflect perinatal stress associated with delivery mode.     

The effect of low-dose aspirin on fetal weight of idiopathic asymmetrically intrauterine growth restricted fetuses with abnormal umbilical artery Doppler indices: a randomized clinical trial

Objective: To investigate the effect of aspirin on fetal weight in fetuses with idiopathic asymmetrical intrauterine growth restriction (IUGR) complicated by abnormal umbilical artery Doppler indices.

Materials and methods: The study was a randomized controlled trial conducted at Woman’s Health Hospital, Assiut, Egypt, between June 2016 and the January 2017 included 60 pregnant women (28?30 weeks) with idiopathic asymmetrical IUGR associated with abnormal umbilical artery Doppler indices. Women were randomly assigned to group I (aspirin 75?mg) daily for four weeks or group II (no intervention). The primary outcome was the fetal weight after four weeks. Secondary outcomes included Doppler blood flow changes in the umbilical artery plus delivery and neonatal outcomes.

Results: The estimated fetal weight and umbilical artery blood flow increased significantly in aspirin group (p?=?.00) when compared with no intervention group. As regard neonatal outcomes; aspirin group showed better results and encouraging outcomes (p?Conclusions: Aspirin improves fetal weight and umbilical artery blood flow in idiopathic asymmetrical IUGR fetuses complicated by abnormal umbilical artery Doppler blood flow.     

Serum fetuin-A/alpha2-HS-glycoprotein in human pregnancies with normal and restricted fetal growth

Objective. To investigate circulating concentrations of human fetuin-A (important fetal glycoprotein, involved in vascular pathology and bone metabolism) in mothers, fetuses and neonates from intrauterine-growth-restricted (IUGR, associated with low bone mass at birth and metabolic syndrome in adult life) and appropriate-for-gestational-age (AGA) pregnancies.

Methods. Serum fetuin-A concentrations were prospectively measured in 40 mothers, the doubly-clamped umbilical cords (representing fetal state) and their 20 IUGR and 20 AGA full-term neonates on postnatal day 1 (N1) and 4 (N4).

Results. No significant differences in fetuin-A concentrations were observed between groups, or between maternal, fetal and neonatal samples in both groups. In the AGA group, maternal fetuin-A concentrations positively correlated with fetal and N1 ones (r = 0.599, p = 0.005 and r = 0.469, p = 0.037, respectively). In the IUGR group, maternal fetuin-A concentrations positively correlated with N4 ones (r = 0.541, p = 0.014).

Conclusion. Serum fetuin-A concentrations do not differ between IUGR cases and AGA controls. Maternal and fetal fetuin-A concentrations are similar and positively correlated, indicating the likelihood of passive transplacental transfer of this substance.     

Perinatal sclerostin concentrations in abnormal fetal growth: the impact of gestational diabetes

Objective: To prospectively evaluate maternal and cord blood concentrations of sclerostin – an osteocyte-secreted factor, inhibiting osteoblast differentiation and bone formation and associated with adverse metabolism – in pregnancies with normal and abnormal fetal growth.

Methods: Plasma sclerostin concentrations were determined by ELISA in 80 maternal and 80?cord blood samples from asymmetric intrauterine-growth-restricted (IUGR, n?=?30), large-for-gestational-age (LGA, n?=?30), and appropriate-for-gestational-age (AGA, n?=?20) singleton full-term pregnancies. Fourteen out of 30 mothers with LGA offspring presented with gestational diabetes mellitus (GDM).

Results: Maternal and fetal sclerostin concentrations did not differ among LGA, IUGR, and AGA groups. Fetal concentrations were higher than maternal. In LGA group, maternal concentrations were elevated in cases of GDM (b?=?13.009, 95%CI 1.425–24.593, p?=?.029). In a combined group and the IUGR group, maternal concentrations were elevated in older mothers (b?=?0.788, 95%CI 0.190–1.385, p?=?.010, and b?=?0.740, 95%CI 0.042–1.438, p?=?.039, respectively).

Conclusions: Maternal and fetal sclerostin concentrations may not be differentially regulated in pregnancies complicated by abnormal fetal growth. Circulating maternal levels are higher in cases of GDM, probably implying reduced bone formation. Sclerostin up-regulation with aging may be one of the molecular pathways responsible for the observed age-related decline in bone synthesis, leading to accelerated bone loss in humans.     

Fetal biometry: does patient ethnicity matter?

Abstract

Objective: To determine if fetal biometry varies according to race.

Methods: We performed a retrospective chart review of prenatal ultrasounds completed in our Perinatal Center from January 2009 to December 2010. Singleton pregnancies 17 to 22.9 weeks were included. Pregnancies complicated by IUGR, fetal anomalies, chronic maternal diseases, or dated by an ultrasound after the first trimester were excluded. Biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), and humerus length (HL) were compared between African Americans (AA), Caucasians, and Hispanics using ANOVA and Student t-test.

Results: Included were 1327 AA, 147 Caucasian, and 86 Hispanic subjects. The AC was significantly smaller in AA than Caucasians (p?=?0.008). There was no difference between AA and Caucasians in BPD, HC, FL, or HL. There were no differences between Hispanics and either Caucasians or AA in any of the biometries evaluated.

Conclusions: A single fetal growth curve is not applicable across all ethnicities. AA fetuses have smaller AC then Caucasian fetuses from 17 to 22.9 weeks, which is typically the period when anatomic surveys are performed. Because AC contributes heavily to estimated fetal weight calculations, physicians may be over estimating growth restriction in AA patients. Ethnicity-specific fetal growth curves are indicated to limit unnecessary follow up.     

Discordant clinical presentations of preeclampsia and intrauterine fetal growth restriction with similar pro- and anti-angiogenic profiles

Abstract

Objective: To evaluate the plasma levels of angiogenic factors in preeclampsia (PE) and intrauterine fetal growth restriction (IUGR) and their potential as biomarkers to distinguish normal from pathologic pregnancies.

Methods: Case control study included singleton pregnancies in four categories: (i) normal (n?=?29), (ii) PE (n?=?15), (iii) PE and IUGR (n?=?16) and (iv) IUGR (n?=?24). The classification of IUGR included umbilical artery Doppler resistance. Maternal plasma placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble kinase domain receptor (sKDR) and soluble endoglin (sEng) as well as fetal umbilical artery sFlt-1 levels were determined. Each individual marker and their ratios were assessed for their potential to distinguish normal pregnancy from pregnancies affected by PE and/or IUGR.

Results: We found (i) elevated plasma sFlt-1, sEng and reduced PlGF, sKDR in PE and IUGR; (ii) similar angiogenic profiles in PE and IUGR and (iii) sEng and sFlt-1*sEng/PlGF performed best as biomarkers in identifying pathologic pregnancies.

Conclusions: PE and IUGR have similar angiogenic profiles, suggesting that angiogenic marker profiles lack specificity in identifying PE and that other factors are required for the development of PE instead of IUGR. sEng should be included in a biomarker profile for predicting PE or IUGR.     

Fetal pancreatic Langerhans islets size in pregnancies with metabolic disorders

Objective: Metabolic disorders are a pandemic and increasing health problem. Women of childbearing age may also be affected, thus an abnormal metabolism may interfere with pregnancy short- and long-term outcomes, harming both mother and child. In the context of an abnormal maternal and intrauterine metabolic milieu the development of fetal organs, including pancreas, may be affected.

Aim: To investigate the effects of pregnancy metabolic disorders on the morphology of pancreatic Langerhans islets in human late-third trimester stillborn fetuses.

Methods: Samples from fetal pancreas underwent a quantitative histological evaluation to detect differences between pregnancy with (cases, n?=?9) or without (controls, n?=?6) abnormal metabolism.

Results: Results show that the islets size increases in fetuses from dysmetabolic pregnancies and that this increment is related to both beta-cell hyperplasia and hypertrophy. Moreover, according to pregnancy and fetal metabolic disorders, a threshold of abnormal size of the islets has been identified. Above this threshold the size of fetal pancreatic Langerhans islets should be considered excessively increased.

Conclusion: The study suggests that an accurate fetal pancreas analysis supplies an important tool in stillborn fetus, to discover metabolic disturbances that should be kept in mind and managed in future pregnancies.     

The association of first trimester uterine arteries Doppler velocimetry with different clinical phenotypes of hypertensive disorders of pregnancy: a longitudinal study

Introduction: Current classification of hypertensive disorders of pregnancy (HDP) is mostly based on temporal classification differentiating HDP according to early and late onset of the disease. However, epidemiological and clinical data suggest that there are two different clinical phenotypes of HDP that coexist at any gestational age: HDP associated to intrauterine growth restriction (HDP-IUGR) and HDP associated to appropriate for gestational age fetal growth (HDP-AGAf). The aim of the study was to evaluate the association of first trimester uterine arteries (UtA) by Doppler velocimetry, and maternal risk factors with HDP according to two different classifications: one based on gestational age at delivery (early- and late-HDP), and one based on longitudinal ultrasound evaluation of fetal growth (HDP-IUGR and HDP-AGAf), independently of the gestational age.

Methods: Maternal characteristics and mean pulsatility index (PI) of UtA were collected at 11–13 gestational weeks. A longitudinal ultrasound follow-up of fetal growth in each trimester and clinical outcome were obtained in 4290 singleton pregnancies.

Results: UtA-PI was significantly higher in women who developed HDP-IUGR (n?=?22) and the odds ratio (OR) to develop HDP-IUGR from 25 to 39 weeks was 8.6 (p?n?=?112) was significantly associated with a higher BMI, multiparity, and maternal age, but not with UtA-PI (OR 1.3; p?=?.2). In women with an abnormal UtA-PI, the odds of developing early (n?=?15) and late-HDP (n?=?119) were 3.0 (p?=?.03) and 1.7 (p?=?.002), respectively. The AUCs for HDP-IUGR and early-HDP were 0.84 and 0.71, respectively.

Discussion: UtA Doppler velocimetry in the first trimester was strongly associated with HDP-IUGR all along gestation, as a proxy of placental insufficiency, and showed no association with HDP-AGAf. Our findings suggest an efficacy of first trimester UtA Doppler velocimetry to identify HDP-IUGR independently of the gestational age, and a limited value for HDP not associated with intrauterine growth restriction (IUGR).     

Plasma amino acid concentrations throughout normal pregnancy and early stages of intrauterine growth restricted pregnancy

Objectives: Assessment of maternal plasma amino acids during normal gestation and in early stages of intrauterine growth restriction (IUGR).

Study design: Plasma amino acid concentrations were measured in: (1) non-pregnant women (n?=?7); (2) normal pregnant women in the first (n?=?13), second (n?=?17) and third (n?=?12) trimester; and (3) pregnant women in the first trimester with later development of IUGR (n?=?8). Amino acid levels were quantified by electrochemical detection in a reversed-phase high-performance liquid chromatography (HPLC) system.

Results: The levels of most essential and non-essential amino acids changed markedly in the first trimester during normal pregnancy and thereafter remained almost constant. In the first trimester of IUGR, a number of both essential and non-essential amino acids were significantly different from those observed in normal pregnancies, with values more similar to those observed in non-pregnant women.

Conclusions: Levels of most maternal amino acids decrease and some increase during early gestation reflecting a metabolic adaptation that occurs in normal pregnancies. Pregnancies that later develop IUGR show a lack of these adaptations for a significant number of both essential and non-essential amino acids, suggesting a lack of adaptation.     

Utility of Head/Abdomen Circumference Ratio in the Evaluation of Severe Early-Onset Intrauterine Growth Restriction

ObjectiveTo determine whether the predominant phenotype of intrauterine growth restriction (IUGR) is symmetric or asymmetric in severe, early-onset disease due to placental insufficiency.MethodsWe conducted a retrospective chart review of high-risk pregnant women with severe, early-onset IUGR who were delivering at < 33+0 weeks’ gestation at Mount Sinai Hospital from 2001 to 2010. Ultrasound images were reviewed for fetal biometry, amniotic fluid volume, and uterine and umbilical Doppler flow studies within seven days of delivery, and the frequency of head circumference/abdominal circumference ratio ≥ 95th percentile for gestation was determined.ResultsSixty-two of 107 pregnancies (58%) with early-onset IUGR had an elevated HC/AC ratio (≥ 95th percentile), which was more than 10-fold greater than the expected proportion (P < 0.001). High rates of severe preeclampsia (53%), abnormal amniotic fluid (70%), and abnormal uterine artery Doppler studies (78%) indicated placental insufficiency.ConclusionFetuses with severe placental IUGR in the second trimester are more likely to have an asymmetric phenotype. This is in contrast to the current belief that asymmetric IUGR is confined to third trimester IUGR.     

Pregnancy outcome after multifetal pregnancy reduction

Objective: To study the effects of multifetal pregnancy reduction (MFPR) as a means to reduce the adverse outcome of multiple gestations.

Methods: This was a retrospective study evaluating the outcome of 334 multiple pregnancies after embryo reduction.

Results: In 313 multiple pregnancies in which MFPR was performed before 15 weeks, the rates of miscarriage, preterm delivery <?33 weeks, preterm delivery <?36 weeks and total fetal loss were 9.12%, 13.33%, 38.60% and 16.25%, respectively, and median gestational age at delivery was 35 weeks. There was a significant correlation between miscarriage and the finishing number of fetuses. In 185 triplets reduced to twins, miscarriage, preterm delivery <?33 weeks, preterm delivery <?36 weeks and total fetal loss occurred in 8.25%, 11.18%, 40.59% and 15.41% of cases, respectively, and median gestational age at delivery was 36 weeks. In the subgroup of 32 reduced triplet pregnancies that also had second-trimester amniocentesis, the risk of miscarriage (3.13%) was not significantly different from that in the rest of the group. Among 21 twin pregnancies that had selective termination at or after 15 weeks, the risk of preterm delivery <?33 weeks was three times higher than in the group of 22 twin pregnancies with first-trimester procedures.

Conclusion: MFPR resulted in at least one live neonate in 83.75% of cases and was effective in reducing the risks of pregnancy loss and severe prematurity in quadruplets and higher-order pregnancies. The risk of miscarriage increased with increasing finishing number of fetuses. In reduced triplets gestation was prolonged in comparison with average figures reported in the literature. In twin pregnancies selective termination in the first trimester carries a lower risk of severe preterm delivery and this emphasizes the need for first-trimester diagnosis.     

Placental gene expression patterns of endoglin (CD105) in intrauterine growth restriction

Abstract

Objective: In this study, we describe placental gene expression patterns of endoglin in pregnancies with intrauterine growth restriction (IUGR) compared to normal pregnancies.

Methods: Placental samples were obtained from 101 pregnancies with IUGR using 140 normal pregnancy cases as control. Gene expression patterns and protein levels of the endoglin were compared between the two groups. For the gene expression analysis real-time PCR was applied, while for the estimation of placental protein level we performed Western analysis.

Results: The placental endoglin gene was significantly overexpressed in the IUGR group versus the control group (Ln2^α: 1.69). The placental endoglin protein level proved to be significantly higher in case of IUGR (endoglin/β-actin ratio: 13.8?±?2.3) versus the control cases (5.3?±?1.1). The placental gene expression as well as the protein levels of endoglin showed no significant difference between female and male newborns. Concerning the placental gene expression and protein level, no significant difference was justified between the more (0–5 percentile) and less (5–10 percentile) severe cases of IUGR.

Conclusion: Increased placental gene expression of endoglin may result in vascular dysfunction leading to chronic fetal hypoxia, which may induce VEGF-A to stimulate angiogenesis. This can be explained as feed back response to restore fetal placental circulation.