Volume 40, Issue 2

Twin-to-twin transfusion syndrome (TTTS) affects about 10% of monochorionic pregnancies and develops when uncompensated unidirectional blood flow from one twin (‘donor’) to the other (‘recipient’) causes circulatory imbalance. The cardiac effect of the underlying hypervolemia or endocrine dysregulation, or both, manifests in the recipient as echocardiographic findings of the syndrome-related cardiomyopathy. The Quintero staging system for TTTS has recently been questioned, because more refined measurement of cardiac function may improve evaluation of disease severity and prediction of outcome. Much has been done to increase survival and diminish the cardiac morbidity associated with TTTS. The purpose of this paper was to review the literature on cardiac morbidity associated this syndrome.

Objective: Which physical findings and blood parameters predict postpartum hypertension remain to be studied in women with twin pregnancies. Methods: The antenatal systolic and diastolic blood pressures (SBP and DBP, respectively), and 16 laboratory variables were investigated in 150 normotensive women who gave birth to twins. Results: When the median values of the 18 continuous variables were used as cut-off values, an SBP>120 mm Hg (relative risk [95% confidence interval], 2.81 [1.94–4.08]), a DBP>70 mm Hg (2.42 [1.68–3.49]), an aspartate aminotransferase level>18 U/L (2.22 [1.55–3.19]), and a uric acid level>5.3 mg/dL (1.68 [1.20–2.36]) were independent risk factors for postpartum hypertension. Conclusions: Antenatal blood pressure measurements and a laboratory work-up may be useful clinically for predicting postpartum hypertension in women with twin pregnancies.

Objective: Hypothesising that maternal serum chemerin levels may be associated with preeclampsia, we investigated whether maternal serum chemerin levels differ between preeclamptic and healthy pregnant women. We also investigated the association of serum chemerin with metabolic parameters and the severity of the disease. Methods: This case-control study included 144 women (72 healthy and 72 preeclamptic women) in the third trimester of a singleton pregnancy. Clinical data and maternal serum were collected. The two groups were carefully matched for maternal age and gestational age. The maternal levels of serum chemerin were determined by enzyme-linked immunosorbent assay. Results: The serum chemerin levels were found to be significantly increased in the women with preeclampsia (258.85±86.64 ng/mL) as compared with the healthy pregnant controls (210.80±47.34 ng/mL) (P<0.001). The serum chemerin concentrations in the severely preeclamptic women (289.6±74.43 ng/mL) were higher than those in the mildly preeclamptic women (228.1±87.99 ng/mL) (P<0.001). A stepwise regression analysis showed that the serum chemerin levels significantly and positively correlated with systolic blood pressure (P<0.001), free fatty acids (P<0.05) and serum creatinine (P<0.01). Conclusions: Chemerin levels are significantly increased in preeclampsia and independently associated with markers of dyslipidemia and with the severity of the preeclampsia. Further studies need to show the onset of the chemerin increase and its putative involvement in the pathophysiology of preeclampsia.

Objective: To compare the expression of sex hormone binding globulin (SHBG) in normal placental tissues with placental tissues from patients with gestational diabetes mellitus (GDM) and to deduce the mechanism affecting placental SHBG in GDM. Methods: We detected SHBG localization and measured SHBG mRNA and protein using immunohistochemistry, reverse-transcription polymerase chain reaction, and Western blotting, respectively, in normal and GDM placental tissues. The distribution of SHBG in placental cells was examined using immune electron microscopy. Results : Compared to controls, placental tissues from patients in the GDM group displayed disordered cell surface microvilli that were decreased in quantity, swollen, and had narrowed and broken gap junctions. Intracellular abnormalities included expanded rough endoplasmic reticula, swollen mitochondria, and irregular nuclear morphologies with non-uniform chromatin. SHBG localized primarily to trophoblast cell membranes and cytoplasm. SHBG was strongly expressed on the microvilli side and weakly expressed on the basement membrane with uneven staining. SHBG also was expressed in villous stromal cells and vascular endothelial cells. Compared to the controls, placental tissues from the GDM group displayed significantly decreased immunostaining rates for SHBG, as well as significantly lower levels of SHBG mRNA and protein expression (P<0.05). Conclusion: SHBG was detected in placental trophoblast cells from patients with GDM, and the synthesis and secretion of SHBG were reduced when trophoblast cells were irregular. A decrease in SHBG could affect placental function or aggravate GDM. Our results suggest that placental SHBG plays an important role in the pathogenesis of GDM.

Aims: Animal research has demonstrated that boron has effects on triglycerides and glucose and may act as a metabolic regulator in several enzymatic systems. Gestational diabetes mellitus (GDM) is a prevalent obstetrical complication and the lack of data on maternal status of boron in normal/diabetic pregnancies, prompted us to undertake this study. Methods: Maternal blood samples were collected during screening and diagnosis of GDM at 24–28 weeks. Serum lipids (total cholesterol, high-density cholesterol, low density cholesterol, triglycerides, lipoprotein-a, apolipoprotein-A-I and apolipoprotein-B) and boron levels were determined. Fifteen non-GDM and 19 GDM women constituted the study population. Results: The mean age was 30.1±5 years. The median boron levels were 15.2 μg/L (0.0152 ppm; range, 8.4–25.4 μg/L). When GDM and non-GDM cases were compared for age, gravidity, parity, lipid profiles and serum boron levels, no significant differences were found (P>0.05). No correlation was found between lipids and boron levels. Conclusion: This preliminary study contributes to the limited information about the metabolic aspects of boron. Considering the evidence that boron acts as a regulator of energy substrate utilization, the effect of dietary boron on glucose metabolism deserves further research.

Objective: To examine the association of maternal hemoglobin (Hb) concentrations with preterm and low birth weight (LBW) deliveries in African Americans compared to Caucasians. Methods: We conducted a retrospective analysis of perinatal data on 17,338 African-American and Caucasian pregnant women who delivered at the George Washington University Hospital (GWUH) between January 1990 and December 2003. We used univariate and logistic regression analyses to examine for associations. Results: Compared to Caucasians (n=9432), African American mothers (n=7906) had a higher incidence of anemia (26.9% vs. 7.1%, P<0.001), preterm (22.1% vs. 12.8%, P<0.001) and LBW (18.6% vs. 9.7%, P<0.001) outcomes. This association increased with decreasing Hb concentrations in each race. Risk for preterm and LBW outcomes were higher in African Americans compared to Caucasians at Hb concentration ≥12 g/dL (P<0.007); however, there were no race-specific risk at Hb concentration <11 g/dL (P>0.05). Conclusions: The association of race with preterm and LBW outcomes relates to maternal Hb. Our findings suggest: a) anemia is a strong risk factor that masks the influence of race, b) African American race could be a surrogate for other factors that contribute to adverse outcomes, and c) Caucasian race could be less adaptive to anemia.

Aims: To develop a model based on non-invasive clinical parameters to predict the probability of imminent preterm delivery (delivery within 48 h) in women with preterm premature rupture of membranes (PPROM), and to determine if additional invasive test results improve the prediction of imminent delivery based on the non-invasive model. Methods: Transvaginal ultrasonographic assessment of cervical length was performed and maternal serum C-reactive protein (CRP) and white blood cell (WBC) count were determined immediately after amniocentesis in 102 consecutive women with PPROM at 23–33+6 weeks. Amniotic fluid (AF) obtained by amniocentesis was cultured and interleukin-6 (IL-6) levels and WBC counts were determined. Results: Serum CRP, cervical length, and gestational age were chosen for the non-invasive model (model 1), which has an area under the curve (AUC) of 0.804. When adding AF IL-6 as an invasive marker to the non-invasive model, serum CRP was excluded from the final model (model 2) as not significant, whereas AF IL-6, cervical length, and gestational age remained in model 2. No significant difference in AUC was found between models 1 and 2. Conclusions: The non-invasive model based on cervical length, gestational age, and serum CRP is highly predictive of imminent delivery in women with PPROM. However, invasive test results did not add predictive information to the non-invasive model in this setting.

Objective: Placement of a cervical cerclage at mid-trimester in women at risk for preterm labor is a common procedure with apparent benefits for some women. However, the changes that occur in the cervix following this procedure remain incompletely identified. Methods: We evaluated the endocervical concentrations of mediators involved in extracellular matrix (ECM) stabilization or degradation prior to, and up to 120 days following, cerclage placement in 53 women who underwent an ultrasound-indicated or a rescue cerclage at 15–25 weeks of gestation due to a cervical length <1.5 cm. All delivered a healthy neonate at term. Samples were tested by enzyme-linked immunosorbent assay for concentrations of hyaluronan (HA), 27 kDa heat shock protein (hsp27), transforming growth factor-β (TGF-β), extracellular matrix metalloproteinase inducer (CD147/EMMPRIN), and matrix metalloproteinase (MMP)-1 and -8. Results: Concentrations of both HA and hsp27 were highest at the time of cerclage placement and then decreased while TGF-β and EMMPRIN increased in concentration following the procedure. The highest mean EMMPRIN level was measured at >90 days following the procedure while TGF-β levels peaked at 61–90 days post-cerclage. MMP-1 and MMP-8 were not detected over the study time period. Conclusion: In women with a successful cerclage placement the selective regulation of mediators inhibits progression of ECM degradation and cervical ripening.

If maternal atopy and environmental exposure affect prenatal Th cell development, the maternal and fetal immune systems should display common Th1/Th2 phenotypes. To test this hypothesis, we studied maternal and neonatal blood samples from mothers with total serum IgE <300 IU/mL. Basal levels of IFN-γ, IL-4, and eotaxin in paired maternal and fetal sera were tightly correlated. Polyclonal T cell activation in vitro by Staphylococcal exotoxin B induced co-ordinate IFN-γ production from paired maternal and fetal mononuclear cells, accompanied by co-ordinate increases in activated CD4+CD69+ cells that display the CCR4+Th2 and CXCR3+ Th1 phenotypes. Maternal and fetal CD4+CXCR3+ T cells were subsequently identified as the major producers of IFN-γ. The data established that a transplacental nexus exists during normal pregnancy and that fetal Th cell responses may be biased by the maternal immune system.

Aim: To assess the effect of time of active pushing (TAP) on neonatal outcome. Materials and methods: The study population (n=36,432) was taken from a Swedish randomized control trial on intrapartum monitoring, a European Union fetal electrocardiogram trial, and from Mölndal Hospital. After validation of acid-base samples and TAP, 22,812 cases were accepted for analysis. Results: The median active TAP was 36 min for P0 and 13 min for P≥1 (P<0.001). After adjustments for parity, epidural, labor induction, birth weight, and gender, pushing for 15–29 min (n=6589) relative to pushing for <15 min (n=7264) increased the OR of a cord artery pH of <7.00 to 3.20 (95% CI 1.7–6.0), and that of a base deficit in extracellular fluid of >12 mmol/L to 3.5 (95% CI 1.3–9.0). The group with a cord artery pH of <7.00 had a longer TAP than the group with pH≥7.00: median (5 th –95 th percentile), 38 (9–107) min vs. 23 (5–87) min, P<0.001. The probability of a spontaneous vaginal delivery decreased significantly with every subsequent increase of 30 min in TAP (P<0.05). Conclusion: The risks of severe acidemia, metabolic acidosis, and deteriorated neonatal outcome gradually increased with the length of TAP (>15 min), while the probability of a spontaneous vaginal delivery decreased with the duration of pushing. We suggest active physiological evaluation of the labor progress together with continuous electronic fetal monitoring during pushing irrespective of guideline thresholds.

Objective: To assess the age-dependent fetal subcutaneous fat layer (SCFL) of non-diabetic, normal-weight mothers and fetuses of mothers with gestational diabetes (GDM) and normal body weight or obesity. Methods: In a prospective study, we evaluated 115 MRI examinations of fetuses with no history of (maternal) metabolic disease [gestational week (GW) 29 to 39/40] and 50 examinations of mothers with GDM and normal body weight or obesity. The SCFL was measured at predetermined anatomical landmarks. Measurements were correlated with the maternal body mass index (BMI) and glycated hemoglobin A1c (HbA1c)-values in diabetic mothers. Results: In fetuses of non-diabetic, normal-weight mothers, measurements showed high consistency within the respective GW and ranged from 2 mm at GW 29 at all measured points, up to 4.5 mm at the trunk and 6.0 mm at the extremities at GW 39/40. In 47/50 fetuses of mothers with GDM, the SCFL was within the range of fetuses of mothers with no metabolic disease. In three patients with GDM and BMI<30, the SCFL-thickness was decreased. No fetuses showed an increased SCFL-thickness. Conclusion: The SCFL of normally developed fetuses is easily detectable from GW 29 on T1-weighted images (T1-W), and increases with gestational age. The presented data provide physiological benchmarks to evaluate developmental status and may help in the prenatal diagnosis of abnormal growth and macrosomia. In pregnant women with well-controlled GDM, an increase of the SCFL is not expected.

Background: Antenatal magnesium sulfate can potentially reduce the risk of cerebral palsy in neonates delivered between 24 and 32 weeks of gestational age. Some studies using high-dose magnesium sulfate for neuroprotection have reported increased perinatal mortality. Methods: A retrospective study was conducted on 475 neonates born between 24 and 32 weeks of gestational age. Serum magnesium level in the first 24 h of life was used to stratify the neonates treated with antenatal magnesium into four subgroups: A (<2.5 mEq/L), B (≥2.5 to <3.5 mEq/L), C (≥3.5 to <4.5 mEq/L), and D (≥4.5 mEq/L). Primary outcome of survival without intraventricular hemorrhage (IVH) and/or periventricular leukomalacia (PVL) along with secondary outcomes, such as Apgar scores, resuscitation, intubation, broncho-pulmonary dysplasia, retinopathy of prematurity (ROP), patent ductus arteriosus (PDA), time to reach full feeds, length of stay (LOS), and mortality during immediate neonatal period were studied. Results: Of the 475 neonates included in the study, 289 (61%) received antenatal magnesium sulfate. Primary outcome of survival without IVH and/or PVL among the preterm neonates was 70.9% in those receiving and 74.2% in those not receiving antenatal magnesium (P=0.25). There were higher incidences of ROP (P=0.02), PDA (P=0.01), greater time to reach full feeds (P=0.03), and increased LOS (P=0.01) in neonates who had received antenatal magnesium. These findings were not statistically significant when the data were corrected for gestational age and birth weight. Among the subgroups, there was a significantly increased mortality rate (P<0.05) with increasing magnesium levels (5% vs. 16.9%, P<0.05 in groups A vs. D) and a trend toward higher intubation rate (P=0.1) and PDA (P=0.14). Conclusion: Antenatal magnesium is safe in the immediate postnatal period; however, in the subset of preterm neonates with serum magnesium levels >4.5 mEq/L, there is increased mortality independent of birth weight and gestational age. Identification of these neonates and appropriate dosing for their antenatal neuroprotection needs to be studied.

Aims: Necrotizing enterocolitis (NEC) is an often fatal disease that affects 5–8% of preterm newborn infants but does not occur in older infants and children. As carbon monoxide (CO) may exert protective effects against NEC, we assessed patterns of intestinal injury and investigated the expression of the CO-producing enzyme heme oxygenase-1 (HO-1) in mature and immature rat guts in response to hypercapnia and reoxygenation (H/R). Methods: Gut barrier failure (increased permeability for dextran) was assessed in immature (newborn rats) and mature rats (weanling rats) subjected to H/R. Their guts were assayed for apoptosis (caspase-3 activity), expression of inducible NO synthase (iNOS) and HO-1 [quantitative polymerase chain reaction (PCR) and immunoblot]. The role of HO-1 was investigated in experiments involving HO-1 induction by hemin or HO-1 inhibition by tin protoporphyrin IX. Results: In the mature gut, H/R induced the expression of intestinal HO-1 within 48 h, whereas in the immature gut HO-1 up-regulation was delayed by 48 h. Immature, but not mature, rats exhibited gut barrier failure, apoptosis and increased iNOS expression upon H/R. After the induction of HO-1 by hemin, gut barrier failure and apoptosis were abrogated in the immature gut, while the inhibition of HO-1 by tin protoporphyrin IX significantly aggravated gut injury. Conclusions: These experiments point to an immaturity-dependent lag in HO-1 expression upon H/R in the immature gut and link low HO-1 to gut barrier failure induced by H/R in a non-infectious dam-fed animal model of gut injury.

It is thought that a shallow invasion of the maternal decidua by extravillous trophoblasts (EVT) is associated with the development of pre-eclampsia. Here, we focus on the expression of the proangiogenic proteins Cyr61 and CTGF in the human placenta during normal pregnancy compared with that in the late pre-eclamptic placenta. Cyr61 and CTGF are expressed in the extravillous trophoblast and in endothelial cells. We found the expression of Cyr61 was significantly decreased in pre-eclamptic placentas compared with matched controls. In contrast, the CTGF expression level was upregulated in pre-eclamptic placentas. There was a negative correlation between Cyr61 and CTGF. These results suggest that decreased Cyr61 and overexpressed CTGF may play a part in the development of pre-eclampsia.

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