Role of low placental share in twin-twin transfusion syndrome complicated by intrauterine growth restriction

Objectives

Prior studies have demonstrated that donor twin survival following treatment of twin-twin transfusion syndrome (TTTS) was highly associated with donor intrauterine growth restriction (IUGR). Here, we hypothesized that donor IUGR may be attributed in part to low placental share.

Study design

The study population consisted of all patients who underwent laser treatment for TTTS at a single institution between 2006-2010. Only those pregnancies with dual survival at birth were included so that placental share information could be interpreted. We examined the relationships between Quintero Stage (with separate analysis of Stage III patients with critically abnormal donor Doppler findings) and low placental share (defined as ≤ 30%) with IUGR (<10th percentile) using chi-square analysis and multivariable logistic regression modeling.

Results

Of 210 patients treated, 159 (75.7%) had dual survivors at birth. Of these, placental share was documented in 90 cases (56.6%). Twenty-seven (30.0%) had low placental share, and 37 (41.1%) had IUGR. IUGR was associated with low placental share (63.0% vs. 31.7%, P = 0.0116). IUGR was also associated with Stage III patients (57.4% vs. 23.3%, P = 0.0021), and in particular with Stage III patients with donor involvement (77.8% vs. 25.4%, P < 0.0001). In logistic regression modeling, both low placental share and Stage III with donor involvement were independent risk factors for IUGR (OR = 3.5 [1.2-10.3], P = 0.0206, and OR = 10.1 [3.3-30.6], P < 0.0001, respectively).

Conclusions

Donor IUGR in TTTS pregnancies appears to be associated, in part, with low placental share.     

Placental gene expression of the placental growth factor (PlGF) in intrauterine growth restriction

Objective: We analyzed changes in gene expression of placental growth factor (PIGF) in human placental samples obtained postpartum from pregnancies with IUGR.

Methods: During a twelve-month study period representing the calendar year of 2012 placental samples from 101 pregnancies with IUGR and from 140 normal pregnancies were obtained for analysis of a potential difference in PIGF gene expression.

Results: There was no significant difference in gene activity of the PIGF gene between the IUGR versus normal pregnancy groups (Ln2^α: 0.92; p?α: 0.72; p?=?0.05). Placental PIGF gene activity was significantly lower in fetuses with more severe IUGR versus less severe cases (Ln2^α: ?1.49; p?Conclusion: We found no difference in gene expression of PIGF in placental samples obtained from IUGR pregnancies versus normal pregnancy suggesting the absence of a direct role of PIGF gene activity in the development of defective angiogenesis in IUGR during the later stages of gestation. However, in more severe cases of intrauterine growth restriction PIGF expression does show a significant decrease indicating its potential role in the profound defect in angiogenesis in these cases.     

An animal model of placental insufficiency-induced intrauterine growth restriction

Intrauterine growth restriction (IUGR), often associated with functional placental insufficiency, results in increased perinatal mortality and morbidity. For obvious reasons, many questions regarding the progression of IUGR pregnancies cannot be addressed experimentally in humans, predicating the use of animal models. Although no animal model fully recapitulates human pregnancy, the pregnant sheep has been used extensively to investigate maternal-fetal interactions. In sheep, surgical placement of catheters in both the maternal and fetal vasculature allows repeated sampling from nonanesthetized pregnancies. Considerable insight has been gained on placental oxygen and nutrient transfer and utilization from use of pregnant sheep, often confirmed in the human once appropriate technologies became available. This review will focus on one sheep model, used to examine the impact of placental insufficiency-induced IUGR on oxygen and nutrient transport and utilization.     

Cotyledonary-like placenta associated with severe intrauterine growth restriction

There have been no previous reports of human placentas mimicking the cotyledonary placenta of ruminants. We report a case of cotyledonary-like placenta associated with severe intrauterine growth restriction. A woman pregnant for the first time was referred to our hospital at 27 weeks' gestation because of severe intrauterine growth restriction. Characteristics of the placenta in the patient were examined by ultrasonographical and histopathological techniques. Ultrasonography revealed that a hypo-echoic area intermingled with small segmented tissues in the placenta. The hypo-echoic area changed in size and shape according to uterine contractions. At 31 weeks' gestation, a caesarean section was performed because of non-reassuring fetal status. A female baby weighing 814 g was delivered. The placenta, which weighed 260 g, contained several long stem villi running over a distance of 6 to 7 cm without branching into intermediate or terminal villi. Small villous tissues had developed only at the tips of these stem villi. The present case shows an extraordinarily abnormal development of the villous trees in the placenta, which may have caused fetal IUGR and non-reassuring fetal status.     

Deregulation of imprinted genes expression and epigenetic regulators in placental tissue from intrauterine growth restriction

Journal of Assisted Reproduction and Genetics - Intrauterine growth restriction (IUGR) is a fetal growth complication that can be caused by ineffective nutrient transfer from the mother to the...     

Second trimester amniotic fluid endothelin-1 concentrations and subsequent development of intrauterine growth restriction

OBJECTIVE: The purpose of this prospective study was to record endothelin-1 (ET-1) concentrations in the second trimester amniotic fluid and compare these values in women who developed intrauterine growth restriction (IUGR) later in pregnancy with those with uneventful pregnancies. METHOD: Amniotic fluid was retrieved by amniocentesis from 125 women in the second trimester of pregnancy. The levels of ET1 were measured by a sensitive and specific radioimmunoassay. RESULTS: From the 125 women included in the study 12 had pregnancies that later developed IUGR and 88 had uneventful pregnancies. The ET1 concentration was significantly higher (P<0.005) in women who later developed IUGR than in normal pregnancy (106 pg/ml versus 64.7 pg/ml). CONCLUSION: The amniotic fluid concentration of ET1 is elevated by the second trimester in women who later develop IUGR.     

Maternal serum protein S forms in pregnancies complicated by intrauterine growth restriction

Objectives

The clinical relevance of protein S deficiency in pregnant women remains controversial. Major debate exists regarding which parameter (total protein S antigen, free protein S antigen or functional protein S) should be evaluated in order to define protein S deficiency. The present study aimed to identify which of these parameters correlate with intrauterine growth restriction (IUGR).

Study design

A retrospective case-control study of women with IUGR (n = 27) and healthy controls (n = 123) in the third trimester of pregnancy.

Results

The maternal serum of women in the IUGR group had significantly lower levels of functional and free protein S compared with the control group: 54.07 ± 24.72% vs 65.20 ± 17.95% (p < 0.005) and 42.88 ± 11.01% vs 56.64 ± 13.30% (p < 0.0001), respectively. No significant correlation was found between total protein S and IUGR.

Conclusions

Levels of functional and free protein S are correlated with IUGR.     

Non-placental causes of intrauterine growth restriction

Placental insufficiency, in some form or fashion, is associated with the majority of cases of intrauterine growth restriction (IUGR). There are numerous causes of IUGR which are not caused primarily by placental insufficiency, but indirectly lead to it. The causes of IUGR can be subdivided into fetal and maternal etiologies. The fetal etiologies consist of genetic diseases, congenital malformations, infections, multiple gestations, and placental/cord abnormalities. The maternal etiologies are categorized as follows: (1) decreased uteroplacental blood flow, (2) reduced blood volume, (3) decreased oxygen carrying capacity, (4) nutrition status, (5) teratogens, and (6) miscellaneous causes such as short interpregnancy intervals, race, maternal age, and low socioeconomic status. Knowledge of the etiologies of fetal growth restriction is essential, so that future care can be targeted at prevention. There are several primary and secondary prevention strategies that can be adopted.     

Endothelin 1 and leptin in the pathophysiology of intrauterine growth restriction.

OBJECTIVES: To evaluate the relationship of endothelin 1 (ET-1) and leptin concentrations in women and newborns following a pregnancy complicated with intrauterine growth restriction (IUGR). METHODS: Twenty-five women with a pregnancy complicated with IUGR at 19 different gestational ages were matched with women with uncomplicated pregnancies. Blood samples from the umbilical artery and maternal peripheral venous circulation were collected at delivery, and ET-1 and leptin levels were determined from the blood samples. Data relating to obstetric complications (e.g., pregnancy-induced hypertension), delivery (e.g. mode, birth weight, signs of intrapartum fetal distress, and Apgar scores) were also recorded. RESULTS: Mean maternal ET-1 (13.4+/-6.2-9.9+/-2.9 pmol/l) and mean fetal ET-1 (14.5+/-4.2-11.7+/-3.1 pmol/l) concentrations were significantly higher when women had experienced pregnancies complicated with IUGR than when they had had normal pregnancies. Mean fetal leptin concentration was significantly lower in the study group (6.8+/-2.2 ng/ml) than in the control group (10.6+/-3.6 ng/ml (P<0.05). However, fetal leptin per kilogram of fetal weight was not significantly different in the study group (3.16+/-1.18 ng/ml) than in the control group (3.23+/-0.96 ng/ml) (P>0.05, paired t-test). However, a statistically significant correlation was observed between fetal leptin concentrations per kilogram of fetal weight and fetal endothelin concentrations in pregnancies complicated with IUGR (r=0.546; P<0.05). CONCLUSIONS: These results suggest the intertwined roles of ET-1 and leptin in the pathophysiology of IUGR. Further studies concerning interaction between these peptides in different pregnancy conditions may provide important information about the actions of ET-1 and leptin on fetal growth.     

Umbilical artery Doppler flow velocimetry in intrauterine growth restriction and its relation to perinatal outcome.

OBJECTIVE: The purpose of this retrospective analysis was to compare pregnancy outcomes in growth-restricted fetuses retaining normal umbilical artery Doppler flow and the outcomes of pregnancies with end-diastolic velocity either diminished or severely reduced/absent. METHODS: One hundred pregnant women with growth-restricted fetuses were followed with Doppler velocimetry of the umbilical artery between weeks 28 and 41 of pregnancy. Outcomes were compared for the normal Doppler group (16%), the less-severely abnormal group (77%), and the group with severely reduced or absent end-diastolic velocity waveforms (7%). RESULTS: The diagnosis-to-delivery interval was significantly shorter, and the average birth weight and gestational age at delivery were significantly lower, for fetuses with abnormal Doppler velocimetry (showing diminished or severely reduced/absent end-diastolic velocity) than for those in the normal Doppler group. Fetuses with abnormal Doppler velocimetry also had a significantly higher incidence of oligohydramnios, low-birth weight (<10th percentile), and admission to the Neonatal Intensive Care Unit. There were no perinatal deaths among the normal Doppler patients. CONCLUSIONS: Growth-restricted fetuses with normal umbilical artery velocimetry are at significantly lower risk than those with abnormal velocity waveforms, and immediate delivery of the fetus with diminished end-diastolic flow may be unnecessary. Knowing this relationship may be useful in the clinical management of such pregnancies. Doppler surveillance of growth-restricted fetuses supplemented with cardiotocography, preferably combined with biophysical profile testing, results in a prolonged gestational age and acceptable fetal outcome.     

Suspicion of intrauterine growth restriction: Use of abdominal circumference alone or estimated fetal weight below 10%

Objective. To determine, among patients at risk for intrauterine growth restriction (IUGR), the peripartum outcomes and predictive accuracy for those with normal abdominal circumference (AC) and estimated fetal weight (EFW) for gestational age (GA; group 1) versus those with AC ≤ 10% for GA but EFW>10% (group 2) versus those with AC and EFW ≤ 10% for GA (group 3).

Study design. We identified, retrospectively, non-anomalous singleton pregnancies with reliable GA, and delivery within 21 days of the examination who were referred for possible IUGR. Odds ratios (OR) and 95% confidence intervals (CI) were calculated, as were likelihood ratios (LR) for detection of small for gestational age (SGA) (birth weight ≤ 10% for GA; SGA).

Results. Among the 169 consecutive patients who met the inclusion criteria, the prevalence of SGA was significantly higher for group 3 (80%) than group 1 (42%; OR 4.26, 95% CI 1.94–9.16) or group 2 (49%; OR 5.49, 95% CI 2.13–13.85). The rate of admission to the neonatal intensive care unit (67%, 34%, and 36% for groups 3, 2, and 1, respectively) and the combined perinatal morbidity (35%, 23%, and 15%) were different for the three groups. The LR for detection of SGA was 1.2 (95% CI 1.0–1.4) for group 2 and 2.8 (95% CI 1.6–4.9) for group 3.

Conclusions. Among patients suspected for IUGR, the peripartum outcome is poorest for those with AC and EFW ≤ 10% for GA, than for those with AC ≤ 10% but EFW>10%. The detection of SGA is poor regardless of whether just AC or AC plus EFW are ≤ 10%.     

Reduction of maternal circulating endothelial progenitor cells in human pregnancies with intrauterine growth restriction

Introduction

Circulating endothelial progenitor cells (EPCs) may play a crucial role during pregnancy by sustaining adequate placentation and fetal growth. Unambiguous demonstration of EPC increase during pregnancy has been hampered so far by lack of standardized methods for EPC quantification. In this study we used the currently most accepted phenotype for EPC detection for investigating whether maternal circulating EPCs might increase during normal pregnancy and whether they may fail to increase in pregnancy complicated by idiopathic intrauterine growth restriction (IUGR), a leading cause of perinatal mortality and morbidity characterized by insufficient placental perfusion.

Methods

Twenty-one non-pregnant women, 44 women during healthy pregnancy progression (9, 13 and 22 women in the first, second and third trimester, respectively) and 11 with pregnancy complicated by idiopathic IUGR were recruited in a cross-sectional study. EPCs in maternal blood were identified as CD45^dim/CD34⁺/KDR⁺ cells by flow cytometry. Plasmatic cytokines were measured by ELISA.

Results

We observed a significant and progressive increase of EPCs in normal pregnancy, yet detectable in early pregnancy but even more pronounced in the third trimester. The increase of EPCs was impaired in IUGR-complicated pregnancies at comparable gestational age. The circulating levels of placental growth-factor and stromal-derived-factor-1 were significantly lower in IUGR than normal pregnancies, possibly contributing to EPC impairment.

Conclusions

EPC count in maternal circulation may have a great potential as a novel biomarker for pregnancy monitoring and may represent the target of novel therapeutic strategies designed to prevent adverse pregnancy outcomes often occurring in IUGR.