Volume 39, Issue 4

Preeclampsia is as a leading cause of maternal and perinatal morbidity and mortality. Prevention, early identification, and individualized treatments may become feasible if reliable early biomarkers can be developed. Towards a systems biology framework, this review synthesizes prior linkage studies and genome scans of preeclampsia with candidates identified in a global gene expression microarray analysis of chorionic villus sampling (CVS) specimens from women who sub-sequently developed preeclampsia. Nearly 40% of these CVS candidate genes occurred in previously identified susceptibility loci for preeclampsia. Integration of genetic epidemiologic and functional gene expression data could help to elucidate preeclampsia as a complex disease resulting from multiple maternal and fetal/placental factors that each contributes a greater or lesser effect. These loci and related candidate genes are set to substantially improve insights into the first trimester pathogenesis of this pregnancy disorder.

Background: Some women exhibit a gradual decrease in antithrombin activity until the time of delivery, with antithrombin activity reaching <65% of the normal level (pregnancy-induced antithrombin deficiency, PIATD). However, the clinical features of such women are not well understood and are unfamiliar to many obstetricians. Findings: PIATD is more likely to occur as the number of fetuses increases (approx. 1.0%, 10%, and 40% for singleton, twin, and triplet pregnancies, respectively) and in women with hypertension, isolated proteinuria and/or edema. However, normotensive women account for 60% of women with PIATD. Antithrombin can escape from the blood into the interstitial space. Women with PIATD suffer from a decreased plasma volume and are more likely to develop liver dysfunction, irrespective of the presence or absence of hypertension. Because antithrombin activity continues to decrease until the time of delivery in women with PIATD, women with unrecognized PIATD may be identified as patients with so-called “acute fatty liver of pregnancy” if delivery is delayed. Conclusion: Knowledge of AT activity in obstetrical practice may improve management of pregnant women. The determination of AT activity should be considered in women with multifetal pregnancies, hypertension, isolated protein-uria and/or edema.

Strategies for the prevention of cerebral palsy (CP) remain incompletely characterized. Recognizing that half of all cases are associated with preterm delivery (Australian CP Register Report, 2009), research protocols aimed at reducing its prevalence have focused on interventions in pregnancies at risk for preterm birth. Compelling data from recent clinical trials have led to an emerging consensus favoring the use of antenatal magnesium sulfate for preterm neuroprophylaxis. Unresolved, however, is the critical question regarding the “best dose”. Acknowledging that any substance in high enough doses becomes toxic, the “best dose” is really the least dose that achieves efficacy, while minimizing potential toxicity among susceptible fetuses. Importantly, credible evidence from these CP prevention trials indicates that antenatal magnesium sulfate, if dosed appropriately, may also decrease infant mortality – a worthy goal in its own right. Accordingly, whether we achieve (a) reduction in CP only, (b) simultaneous reduction in CP and infant mortality, or (c) CP reduction offset by possibly increased pediatric mortality, may depend on selection of dose. In this Opinion paper, we review the findings of all major randomized trials that tested the magnesium hypothesis for prevention of CP. In addition, we discuss future research, in progress, that is hoped to refine estimates of best dose.

Aims: To compare the short-term maternal and neonatal outcomes of very low birth weight (VLBW) breech singletons by mode of delivery. Methods: All breech fetuses born from 24-0/7 to 26-6/7 weeks’ gestation at our institution between 2000 and 2008 were eligible for the study. Abstracted medical record data included maternal demographics, delivery data, and neonatal outcomes. Results: There were 26 vaginal and 39 cesarean deliveries. Maternal age did not differ between groups; gestational age was greater in the cesarean group by five days. Short-term neonatal outcomes did not differ between groups. Of the 39 cesarean deliveries, 27 involved classical uterine incisions. Estimated blood loss (732 mL vs. 362 mL) and postpartum infection rate (26% vs. 4%) were greater with cesarean delivery. Conclusion: Neonatal outcome is not improved in VLBW infants born by cesarean section. Given the morbidity of classical cesarean sections, vaginal delivery of the breech VLBW infant may be safely considered.

Objective: To show that the fetal outcome in vaginal deliveries (VD) of breech presentation in a setting of a senior obstetrician stand-by system is as good as in planned cesar- ean sections. Patients and methods: This observational prospective intent-to-treat study (n=211 singleton breech presentation pregnancies of ≥35 weeks of gestation) compared two groups of breech deliveries: planned cesarean sections (PCS, n=126) and intended VD (IVD, n=85) resulting in vaginal deliveries (VD, n=46) as well as secondary cesarean sections (SCS, n=39). Women's informed choice as well as strict pre-selection criteria for vaginally intended breech presentation deliveries was followed. Results: Fetal outcome of vaginal breech deliveries and of primary as well as SCS (45.9% of IVD) was comparable in terms of cord blood pH, base excess, Apgar score, fetal trauma, and transfer to neonatal intensive care unit. Conclusions: Vaginal breech delivery is a safe option in a stand-by system of senior obstetricians with controlled decision-making before labor.

Objective: To analyze the proteomic pattern in urine for distinguishing severe preeclampsia from mild preeclampsia and normotensive controls using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Study design: Urine samples were collected from women with severe preeclampsia (n=11 [sPE]), mild preeclampsia (n=7 [mPE]), and normotensive controls (n=8) and analyzed by SELDI-TOF-MS to identify discriminatory protein peaks in the sPE cohort. A scoring system was constructed – designated as Preeclampsia Proteomic Score of Urine (PPSU) – to differentiate sPE from mPE and normotensive controls. Results: Four discriminatory protein peaks were identified (m/z ratio: 4155, 6044, 6663, and 7971), all of which were down-regulated in women with sPE. PPSU scores in women with sPE were significantly lower than that in both mPE and controls (sPE 0 [0–4] vs. mPE 3 [0–4] vs. controls 4 [2–4]; median [range]; P<0.05). PPSU<2 had a sensitivity of 90.9% and specificity of 93.3% in discriminating patients with sPE from mPE and controls. Conclusion: Proteomic analysis of urine can accurately distinguish sPE from mPE and normotensive controls.

Objective: To compare the efficacy and safety of two methods for induction of labor after previous cesarean section. Methods: To compare 247 women with a previous cesarean section who were induced with a dinoprostone vaginal insert and 279 women with a previous cesarean section induced with oxytocin, between 2001 and 2008. We evaluated vaginal delivery rate, maternal morbidity and newborn morbidity and mortality. Results: The overall rate of vaginal delivery was 65.2%. We did not find significant differences between induction with dinoprostone vaginal insert and oxytocin in the rate of cesarean section performed (35.6% vs. 34.1%, P=0.71). There were nine cases of uterine rupture (rate of 1.7%), of which four occurred with dinoprostone vaginal insert and five when using oxytocin (P=0.89). We found no significant differences in neonatal outcomes. Conclusions: Both tested methods appear to be equally safe and effective for induction of labor in women with a previous cesarean section.

Objective: To assess mid-trimester amniotic fluid concentrations of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and lipopolysaccharide binding protein (LBP) in pregnancies with normal outcome and correlate them with gestational week (GW), parity, and fetal gender. Methods: Cytokine concentrations were measured within a week of amniocentesis during GW 15+0 to 20+6 and correlated with GW at birth, parity, and fetal gender. Results: After exclusion of women with an adverse pregnancy outcome or those lost to follow-up, 273 consecutive patients were evaluated (median parity: 1; range: 0–5). Ranges for IL-6, IL-8, TNF-α, and LBP were 4.9–2620 pg/mL, 36.2–5843 pg/mL, 8.0–28.2 pg/mL, and 0.06–1.9 μg/mL, respectively. IL-6, IL-8, and LBP values did not respectively differ among time points, but TNF-α values did between the 15 th and 16 th and the 15 th and 18 th weeks of gestation (P<0.05). No significant correlations between cytokine levels and parity or fetal gender were identified. Conclusions: Cytokine concentrations in amniotic fluid during the mid-trimester did not differ with parity or fetal gender. IL-6, IL-8, and LBP levels appeared stable with GW, whereas GW significantly influenced TNF-α concentrations. Further analyses are warranted to establish the role of cytokines in predicting adverse pregnancy outcomes.

Objectives: To investigate the expression of laminin receptor 1 (LR1), a non-integrin-type laminin receptor, in preeclamptic and normal third-trimester placentas, as well as to investigate whether its expression differs with disease severity. Study design: Third trimester placental samples obtained from deliveries of preeclamptic (n=34) and normotensive healthy pregnant women (n=35) were immunohistochemically studied for the expression of LR1. The placentas from both mild (n=14) and severe (n=20) preeclamptic pregnancies were further assessed for strength of LR1 expression according to disease severity. Results: When compared with normal placentas, the staining with LR1 protein in cytotrophoblasts and syncytiotrophoblasts was lower in preeclamptic placentas (P<0.05 and P<0.01, respectively). The intensity of staining with LR1 in decidual cells, cytotrophoblasts, syncytiotrophoblasts, and extracellular matrix cells of preeclamptic placentas did not vary with disease severity (P>0.05). Conclusions: Decreased LR1 expression in cytotrophoblasts and syncytiotrophoblasts of preeclamptic placentas, which may be independent of disease severity, might have a role in shallow trophoblastic invasion in preeclampsia.

Objective: To evaluate colonization, transmission rate and serotype distribution of group B streptococci (GBS) in pregnant women and infants born in a single University Center in Germany. Methods: In a prospective study we collected cultures from pregnant women and ear cultures from newborns. We performed serotyping and susceptibility testing. Obstetrical factors associated with mother to infant transmission were analyzed using logistic regression. Results: We evaluated cultures of 869 pregnant women and 845 neonates including 657 paired maternal-neonatal cultures. Maternal colonization occurred in 21.1% (183/869), transmission from mother to newborn in 11.2% (17/152). Intrapartum antimicrobial prophylaxis (IAP) and cesarean delivery were associated with reduction of transmission rate (P=0.014 and 0.019, respectively). The incidence for early-onset disease (EOD) was 1.71 per 1000 live births. Of GBS positive women IAP was administered in only 39% (59/152). Serotype III was the most prevalent isolate (28% maternal; 52% neonatal) and transmission occurred more frequently compared to other serotypes. Conclusions: The incidence of EOD and distribution of serotypes in Germany are similar to published data from the USA prior to 1996. Despite national guidelines with universal GBS screening, our study demonstrated a lack of adherence to this recommendation. There is a need for enhanced compliance.

Aim: The association between infection and inflammatory response in preterm labor (PTL) is well established. Our aim was to elucidate the roles of utero-placental perfusion and fetal component, in PTL. Methods: Histopathologic findings in placentas from pregnancies complicated by preterm birth with or without premature rupture of membranes (ROM) (study group) were compared to placentas from pregnancies with delivery >34 weeks, with or without spontaneous ROM (control group). Placental lesions were classified as those consistent with maternal circulation abnormalities, maternal underperfusion, vascular or villous changes, and those consistent with fetal thrombo-occlusive disease, vascular or villous changes. Lesions were analyzed by maternal or fetal origin of inflammatory response. Results: The study group of 68 women, had a higher rate of vascular lesions than controls (136 women, 26.5% vs. 11%, P=0.005) and of inflammatory lesions of maternal and fetal origin (P<0.001). Within the study group, inflammatory lesions were more common in those with ruptured membrane than in those without (P<0.001). Conclusions: Placentas from preterm birth demonstrate vascular lesions of maternal origin, in addition to the known inflammatory process. Preterm premature membrane rupture is associated with an increased rate of inflammatory lesions relative to spontaneous intact membranes-preterm birth, suggesting a different underlying mechanism.

Objective: To compare perforation characteristics of standard 22 G (0.7 mm) to 29 G needle (0.34 mm) for amniocentesis. Methods: Seventeen human chorio-amnion membranes were perforated immediately after cesarean section using 22 G needle for spinal anesthesia and 29 G “pencil-point” needles for amniocentesis under in-vitro conditions. Area of perforation was determined using a microscope and volume of fluid leakage was measured over a period of 5 min. Results: Membrane perforation with the 22 G needle resulted in a mean damaged area of 225,147.4 μm 2 , a hole with a mean area of 50,154 μm 2 and amniotic fluid volume passage of 17.5 mL/5 min, whereas the 29 G needle generated a mean damaged area of 114,812.4 μm 2 , a hole with an average area of 1382.5 μm 2 and volume passage of 0.28 mL/5 min. These differences were significant. Conclusion: The hole formed by membrane perforation with 29 G “pencil-point” needle for amniocentesis is 36 times smaller, and the amniotic fluid loss is 61 times less than that measured with the 22 G standard needle for spinal anesthesia. Significant reduction of complications following amniocentesis is expected with the 29 G needle.

Objective: To compare outcomes of twin pregnancies with and without gestational diabetes mellitus (GDM). Study design: We compared 105 twin pregnancies with GDM (7.8% of all twin pregnancies) to 315 controls without GDM, matched for gestational age, chorionicity and year of birth. Results: Pre-gravid obesity appears to predispose women to GDM during twin pregnancy [odds ratio (OR) 3.5; 95% confidence interval (CI) 1.7, 7.0]. Overweight and obese women that subsequently developed GDM during their twin gestation were less likely to conceive spontaneously (OR 0.4; 95% CI 0.3, 0.7). Twins from the GDM group had more respiratory distress syndrome (RDS, OR 2.2; 95% CI 1.3, 3.7) and had a three-fold, but not significantly increased perinatal mortality rate. Birth weight characteristics were similar in both groups. Conclusion: Twin pregnancies complicated by GDM might be associated with pre-pregnancy maternal obesity and are at increased risk of RDS and non-significant increased risk of perinatal death.

Several experimental models on adult and newborn animals showed that in cerebral hypoxic-ischemic conditions similar to clinical states the main source of the excessive production of free oxygen radicals is the highly activated xanthine oxidase (XO) enzyme reaction. Long before this data were available, it became known that the main role of allopurinol (AP) is the inhibition of XO. On the basis of these results, many therapeutic trials with AP were performed both in experimental and clinical studies of ischemia and reperfusion. However, it has been shown that only preventive administration of AP has favorable effects. The explanation for the poor results of AP treatment in human fetal brain damage (FBD) cases is that the drug was applied postnatally. The clinical studies performed in healthy laboring mothers whose deliveries were complicated with FBD showed that placental transfer after prenatal administration of AP may be effective in protecting newborns at increased risk of hypoxic-ischemic cerebral damage. Further controlled trials are required to determine if the prophylactic use of the drug might prevent hypoxic-ischemic injuries when the drug is administered immediately prior to impending fetal hypoxia, or even in deliveries at risk of developing hypoxia.

Objectives: To examine if the fetal main pulmonary artery diastolic forward flows (MPADFs) are detected consistently, if the waves from fetal MPADFs coincide with those from atrial contractions, and the reproducibility of the cardiac cycle measurements using this technique. Methods: Two examiners performed a fetal pulsed Doppler echocardiography of the four chamber (4CV), ductal arch (DA) and short axis (SA) views on 44 women with singleton pregnancies. Time intervals between atrial contraction peaks and those between MPADF peaks were compared. Atrioventricular (AV) and ventriculoatrial (VA) intervals were measured from MPADF waves in DA and SA views and compared between observers. Intraclass correlation coefficients (ICCs) were calculated as a measure of inter-observer reproducibility. Results: In all observations, MPADFs were demonstrated. The mean time intervals between atrial contraction peaks from 4CV and those between MPADF peaks from DA and SA views were not significantly different. The mean AV and VA intervals were not significantly different between observers. Comparison of measurements of two observers had substantial agreements. Conclusions: Our data show that MPADFs can be found consistently and coincide with atrial contractions. As cardiac cycle measurements can be done with considerable reproducibility, this technique may be useful in assessing fetal cardiac cycle.

Objective: To demonstrate the visualization of penile abnormalities on fetal magnetic resonance imaging (MRI). Methods: This retrospective study included five fetuses (25+0 to 31+6 gestational weeks) with penile abnormalities, positively depicted on fetal MRI, using prenatal ultrasonography (US) as a standard of reference. On MRI, the penis, as well as the scrotum and testicles, were evaluated. All fetal organs were reviewed to define penile abnormalities as isolated or in association with other anomalies. Furthermore, US and MRI findings were compared. Results: Posterior hypospadias were demonstrated in all five fetuses, and abnormal testicular descent in two. Associated anomalies were present in all five fetuses on MRI, including abdominal/urogenital pathologies in four; brain pathologies in three; and craniofacial, cardiac, musculoskeletal, pathologies each in one fetus, and intrauterine growth retardation in one fetus. Compared to US, additional MRI findings were shown in four of five fetuses. Conclusions: Our MRI results demonstrate the visualization of fetal penile abnormalities and associated pathologies, which may provide information for perinatal management. MRI may show additional findings compared to prenatal US in certain cases.

Aim: To determine the prevalence and types of intrapartum cardiotocography (CTG) patterns and investigate their relationship to moderate acidemia in term fetuses of diabetic mothers. Also, to assess if the combination of fetal electrocardiogram (FECG) and those CTG patterns strengthens the association with moderate acidemia. Material and methods: The material for this study is obtained from the Swedish randomized control trial and the European Union ST-analysis trial. We developed an analytical model for CTG patterns based on the progress in CTG changes, in a longitudinal periodic manner. The model was then combined with information regarding changes in ST interval that indicate threatening asphyxia, and the findings were analyzed to determine correlation with the presence of moderate acidemia at birth. Results: This study involved data of 413 diabetic mothers. A preterminal CTG was more common in the diabetes mellitus (DM) group (6/70, 8.6%) than in the gestational diabetes (GD) group (3/307, 1.0%; P=0.003). For diabetic mothers (i.e., DM+GD) with a normal CTG at the start of monitoring, the presence of FECG data indicating asphyxia significantly increased the likelihood of an umbilical artery pH<7.15 at birth [odds ratio (OR)=3.65, 95% confidence interval (CI)=1.33–10.05]. Among labors where the CTG was non-reassuring at the start of monitoring, no significant association was found between pH<7.15 and indication to intervene according to FECG information (OR=1.51, 95% CI=0.33–7.0). Conclusions: A preterminal CTG is more common in the fetuses of DM than GD mothers during labor. When CTG was normal at the start of recording, the addition of FECG information gave a significant add on information to predict moderate acidemia.

Objective: To examine if assessment of ductus venosus (DV) flow, crown-rump length (CRL) and nuchal translucency (NT) thickness can predict the discordance in birth weight in monochorionic (MC) twin pregnancies resulting in two live births. Methods: In this prospective study, we assessed CRL, NT and DV flow at 11 +0 –13 +6  weeks' gestation in 326 MC twin pregnancies. The study population included 237 pregnancies without major abnormalities or prenatal interventions resulting in two live births. We examined the value of DV flow and discordance in NT and CRL in the prediction of discordance in birth weight. Results: In the 237 MC twin pregnancies the median discordance in birth weight was 8.0% (range 0–42.2%). There was no significant association between discordance in either CRL or NT and discordance in birth weight (P=0.116 and P=0.332). In pregnancies with abnormal DV flow in at least one of the fetuses the median discordance in birth weight was higher than in those with normal DV flow in both twins (13.2% vs. 7.8%, P=0.006). Conclusions: In uncomplicated MC twin pregnancies, abnormal DV flow in at least one of the fetuses is associated with a higher discordance in birth weight than in those with normal flow in both fetuses.

We investigated the stability of thyroid hormones during a mode of continuous drug infusion via polypropylene tubing using the same conditions that would be applied to treating patients in a hospital setting. The diluted thyroid hormones were prepared using aseptic technique, stored at 2–8°C (36–46°F) and tested within 24 h of preparation for stability and percent recovery from within plastic tubing. Experiments were done in duplicate with triplicate sets of readings for each assay point. Only T 4 prepared with 5% dextrose water (D5W) containing 1 mg/mL albumin remained constant, stable, predictable and accurate over time under various conditions. Other methods of preparation lost drug by adhering to the plastic containers and tubing by as much as 40% of starting concentration. T 3 recovery in the presence of 1 mg/mL of albumin was 107±2% (mean±standard error of the mean) of anticipated drug concentrations. We conclude from this series of experiments that to maintain an accurate and stable dosing of patients receiving intravenous thyroid hormones, 1 mg/mL of albumin must be added to the infusate to prevent lost on the plastic intravenous tubing.

Objective: A supracervical cerclage suturing technique with an intracavitary balloon (SCCB) was developed to simultaneously compress bleeding from the placental bed and the outside uterine wall. Study design: Twenty cesarean sections were performed due to placenta previa over three years. The SCCB was used in 13 patients with uncontrolled bleeding after failure of conventional methods. The conventional surgical hemostatic techniques were applied first in patients with copious bleeding due to placenta previa. If bleeding continued, a three-way Foley catheter was inserted into the uterine cavity through the cervix and SCCB was performed. About 50–100 mL of normal saline was infused to inflate the catheter balloon. On the next morning, attempts were made to withdraw the F-catheter but if bleeding started again, another 12 h of pressure was provided. Results: The mean removal time for the intracavitary Foley catheter was 20.6±12.3 h. There was one case of subtotal hysterectomy after the SCCB. All patients were followed for at least 12 months. There were no specific complications related to the procedure. All women returned to their normal menstrual cycles and one had an ongoing third trimester pregnancy. Conclusion: The SCCB is a simple and effective technique to control bleeding associated with placenta previa.

No abstract available

No abstract available