Volume 43, Issue 2

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder of pregnancy. Diagnosis is based on the clinical picture, particularly the presence of pruritus with a deterioration of liver function tests, and typically elevated serum levels of total bile acids. ICP manifests in the second half of pregnancy, predominantly during the third trimester. Symptoms of the disease resolve spontaneously after delivery. Etiology is still not fully understood. Genetic defects in specific transport proteins, elevated levels of sex hormones, and various environmental factors are thought to play a role in the development of this disorder. Although practically benign for the pregnant woman, ICP represents a serious threat to the fetus. It increases the risk of preterm delivery, meconium excretion into the amniotic fluid, respiratory distress syndrome, and sudden intrauterine fetal death. Identifying fetuses at risk of ICP complications remains challenging. The ideal obstetrical management of ICP needs to be definitively determined. The aim of this review is to summarize the current knowledge on fetal complications of ICP and describe management options for their prevention.

Objective: Obesity is an important issue among fertile women as it may affect obstetric and neonatal outcomes. Methods: Obstetric and neonatal outcomes of primiparous women were retrospectively analyzed in non-obese (n=11387) and obese (n=943) women. A subgroup analysis was performed in obese women divided into three groups: Grade I obesity (Group A, n=654), Grade II obesity (Group B, n=192), and Grade III obesity (Group C, n=97). Odds ratios (OR) were expressed with the corresponding 95% confidence intervals (CI). Results: The incidence of gestational diabetes (non-obese, 1.9%; obese, 7.6%; Group C, 19.6%) and preeclampsia (non-obese, 3.3%; obese, 13.5%; Group C, 17.5%) increased with rising weight. The risk of non-elective cesarean section was significantly higher in obese women than in non-obese women (21.7% vs. 13.2%). The risk of extreme preterm birth (before 28 weeks of gestation) doubled in the Grade I obesity group (OR, 2.1; 95% CI, 1.4–3.2) and nearly tripled in women with body mass index ≥35 kg/m 2 (OR, 2.9; 95% CI, 1.7–4.9). Conclusion: Pre-pregnancy obesity is associated with higher incidences of gestational diabetes and preeclampsia. Our study shows that obese women have a higher risk of non-elective cesarean section and preterm birth.

Recent development of three-dimensional (3D) high definition (HD) ultrasound has resulted in remarkable progress in visualization of early embryos and fetuses in sonoembryology. The new technology of HDlive assesses both structural and functional developments in the first trimester with greater reliably than two-dimensional (2D) ultrasound. The ability to visualize not only fetal face, hands, fingers, feet, and toes, but also amniotic membranes, is better with volumetric ultrasound than 2D ultrasound. In this article, detailed and comprehensive structures of normal and abnormal fetuses depicted by 3D HDlive are presented, including various faces of Down’s syndrome and holoprosencephaly, as well as low-set ear and finger/toe abnormalities from the first trimester. Three-dimensional HDlive further “humanizes” the fetus, enables detailed observation of the fetal face in the first trimester as shown in this article, and reveals that a small fetus is not more a fetus but a “person” from the first trimester. There has been an immense acceleration in understanding of early human development. The anatomy and physiology of embryonic development is a field where medicine exerts greatest impact on early pregnancy at present, and it opens fascinating aspects of embryonic differentiation. Clinical assessment of those stages of growth relies heavily on 3D/four-dimensional (4D) HDlive, one of the most promising forms of noninvasive diagnostics and embryological phenomena, once matters for textbooks are now routinely recorded with outstanding clarity. New advances deserve the adjective “breathtaking”, including 4D parallel study of the structural and functional early human development.

Objective: To survey the placental gene expression of inflammatory markers and growth factors in non-smoking obese women with an uncomplicated pregnancy without associated morbidity and delivery at term compared with normal weight women. Methods: Placental tissue samples from 32 obese women (body mass index, BMI≥35.0 kg/m 2 ) were compared with samples from 94 normal weight women (BMI 18.5–25.0 kg/m 2 ) matched for age (±1 year), gestational age (±3 days), parity and mode of delivery. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to analyse toll receptor-2 and -4, interleukin-6 and -8, tumour necrosis factor-α, leptin, adiponectin, insulin-like growth factor-1 and -2, hepatocyte growth factor, hepatocyte growth factor receptor and insulin receptor. Results: There was no significant difference in gene expression in placental tissue samples from obese and normal weight women. Conclusion: We found no difference in the occurrence of inflammatory marker and growth factor mRNA levels in placental tissue samples from a large group of obese women without associated morbidity and with healthy infants compared to a closely matched control group of healthy normal weight women. Compared with the previous studies, this anomalous finding may be explained by the absence of associated morbidity in the obese women in our study.

Background: Pregnant patients with cardiac disease have significantly higher predicted maternal morbidity and mortality compared to the general obstetric population. Published guidelines on optimal management of these patients recommend multidisciplinary care provision. There are few published data on the incidence of haematological complications in pregnant women with cardiac disease, although the data that does exist suggests a relatively high rate of bleeding and thrombotic events. Aims: To determine the outcomes in terms of haematological morbidity occurring within a cohort of pregnant women with cardiac disease in the setting of multidisciplinary care provision. Methods: Patients were identified from a database compiled by the obstetric cardiology service listing all cardiac patients managed in the Rotunda maternity hospital during the period from 2004 to 2011. Data were obtained from the medical and obstetric case notes relating to details of perinatal care and the occurrence of antenatal and postnatal complications. Results: During the 8-year review period, 451 women with cardiac disease were assessed. Fifty-nine were determined to have moderate to high-risk disease. Each received consultant-delivered multidisciplinary care, where written management strategies were agreed by collaborating senior colleagues either preconceptually or in early pregnancy. No venous thromboembolic events occurred and a modest rate of post-partum haemorrhage (approximately 5%) was recorded. There were no maternal deaths. Conclusion: The relatively favourable outcomes observed within our institution highlight the importance of a multidisciplinary approach to the management of pregnant women with cardiac disease, particularly in scenarios where limited published evidence exists to guide management.

Objectives: To evaluate the accuracy of criteria followed by obstetricians when performing a Kristeller maneuver in cases of prolonged second stage of labor. Methods: In this prospective observational study, the station of the fetal head was measured using the angle of progression (intrapartum ultrasound) just prior to the intervention of the managing obstetrician in 52 women with prolonged second stage of labor. The managing obstetricians were blinded to the sonographic results. The decision of performing a Kristeller maneuver was taken by the obstetricians based on digital palpation and their experience. Delivery mode, Apgar score, umbilical artery pH value, episiotomy, perineal tears, bleeding, and time to delivery were recorded. Results: Kristeller maneuver was performed in 36/52 (69.2%) cases. There were no significant differences between the Kristeller and the non-Kristeller group regarding the angle of progression. There were no significant differences between both groups with respect to delivery mode, perineal tears, episiotomy, bleeding, Apgar score, and umbilical artery pH value. Conclusions: Our study failed to define any criteria followed by obstetricians when performing a Kristeller maneuver in cases of prolonged second stage of labor. There was no relation between the angle of progression and the decision to perform a Kristeller maneuver.

Aims: Regional and interinstitutional variations have been recognized in the increasing incidence of caesarean section. Modes of birth after previous caesarean section vary widely, ranging from elective repeat caesarean section (ERCS) and unplanned repeat caesarean section (URCS) after trial of labour to vaginal birth after caesarean section (VBAC). This study describes interinstitutional variations in mode of birth after previous caesarean section in relation to regional indicators in Germany. Material and methods: A cross-sectional study using the birth registers of six maternity units (n=12,060) in five different German states (n=370,209). Indicators were tested by χ 2 and relative deviations from regional values were expressed as relative risks and 95% confidence intervals. Results: The percentages of women in the six units with previous caesarean section ranged from 11.9% to 15.9% (P=0.002). VBAC was planned for 36.0% to 49.8% (P=0.003) of these women, but actually completed in only 26.2% to 32.8% (P=0.66). Depending on the indicator, the units studied deviated from the regional data by up to 32% [relative risk 0.68 (0.47–0.97)] in respect of completed VBAC among all initiated VBAC. Conclusions: There is substantial interinstitutional variation in mode of birth following previous caesarean section. This variation is in addition to regional patterns.

Objective: To investigate the relationship between angle of progression (AoP) on ultrasonography at 37–40 weeks’ gestation and delivery within 7 days. Methods: This prospective study was conducted between January 2013 and May 2013 at Korea University Guro Hospital, Korea. Nulliparous women between 37/0 and 40/3 weeks’ gestation with a singleton fetus, intact membrane, and cephalic presentation from January 2013 to May 2013 were enrolled. To evaluate the cervical parameters of cervical length and AoP, transvaginal and transperineal ultrasonography were performed, respectively. We then assessed the relationship between cervical parameters and onset of labor within 7 days by multivariate logistic regression analysis. Results: Women who underwent spontaneous onset of labor within 7 days had a significantly shorter cervical length and AoP than those who underwent labor after 7 days. Logistic regression analysis showed that a larger AoP was an independent predictor of spontaneous labor within 7 days. Conclusions: A larger AoP was significantly associated with spontaneous onset of labor within 7 days. These findings may be useful for counseling patients regarding the management of term pregnancies.

Aims: A placenta with hepatitis B virus (HBV) is one of the main reasons for transplacental transmission during pregnancy. This study aims to explore the factors influencing the presence of hepatitis B surface antigen (HBsAg) in the placenta and the synergistic effect of these factors. Methods: A total of 155 placentae and blood specimens were collected from HBsAg-positive mothers and their newborns. HBsAg in placenta was detected using the immunohistochemistry method. HBV serum markers were detected using enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) methods. Results: The results showed that hepatitis B e antigen (HBeAg) positive, or HBV DNA positive status, is significantly associated with an HBsAg-positive placenta. A synergistic effect was present. The hazard ratio for a HBsAg-positive placenta in mothers with HBeAg and HBV DNA was 1.97 times higher than the sum of the independent relative risk of each separate effect (synergy index, S=1.97). There was a statistically significant association between HBsAg in newborns and HBsAg in placenta, and the risk of newborns with HBsAg was greater (odds ratio values 3.33 and 5.31, respectively) when placental cells close to the fetal side were HBsAg positive. Conclusions: Being positive for HBeAg and/or HBV DNA are significant risk factors for HBsAg in the placenta. HBsAg can pass through the placenta via cellular transfer, possibly contributing to transplacental transmission.

Objectives: Data on sarcoidosis in pregnancy is sparse and limited to a few case reports and series. Our aim is to determine the prevalence of sarcoidosis at delivery, and related maternal and newborn outcomes. Study design: Using the United States Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) from 2003 to 2010, we conducted a population-based retrospective cohort study to compare women with and without sarcoidosis at delivery. We calculated the prevalence of sarcoidosis in pregnancy and used logistic regression analyses to estimate the associated risks of maternal and neonatal outcomes. Results: There were 678 cases of sarcoidosis in 7,094,400 births over an 8-year period for an overall prevalence of nine and six-tenths cases per 100,000 births. Compared with controls, women with sarcoidosis were older, more likely to be African American and to report being smokers. Women with sarcoidosis were more likely to have preeclampsia odds ratio (OR) 1.62 (95% CI 1.18–2.22), eclampsia OR 5.27 (95% CI 1.69–16.40), deep vein thrombosis OR 4.92 (95% CI 1.58–15.33), pulmonary embolism OR 6.68 (95% CI 3.99–11.21), and premature delivery OR 1.73 (95% CI 1.40–2.15). There was also an increased risk of cesarean deliveries and postpartum hemorrhages. There were no cases of maternal death reported. Conclusions: Sarcoidosis in pregnancy is a rare disease associated with an increased risk of adverse obstetrical outcomes. Women with sarcoidosis can carry out successful pregnancies, however should be made aware of the higher risk of adverse events. Given the higher risk of venous thromboembolic events, consideration should be given to thromboprophylaxis in pregnancy.

Objectives : Our two objectives were to evaluate the feasibility of fetal brain magnetic resonance imaging (MRI) using a fast spin echo sequence at 3.0T field strength with low radio frequency ( rf ) energy deposition (as measured by specific absorption rate: SAR) and to compare image quality, tissue contrast and conspicuity between 1.5T and 3.0T MRI. Methods : T2 weighted images of the fetal brain at 1.5T were compared to similar data obtained in the same fetus using a modified sequence at 3.0T. Quantitative whole-body SAR and normalized image signal to noise ratio (SNR), a nominal scoring scheme based evaluation of diagnostic image quality, and tissue contrast and conspicuity for specific anatomical structures in the brain were compared between 1.5T and 3.0T. Results : Twelve pregnant women underwent both 1.5T and 3.0T MRI examinations. The image SNR was significantly higher (P=0.03) and whole-body SAR was significantly lower (P<0.0001) for images obtained at 3.0T compared to 1.5T. All cases at both field strengths were scored as having diagnostic image quality. Images from 3.0T MRI (compared to 1.5T) were equal (57%; 21/37) or superior (35%; 13/37) for tissue contrast and equal (61%; 20/33) or superior (33%, 11/33) for conspicuity. Conclusions: It is possible to obtain fetal brain images with higher resolution and better SNR at 3.0T with simultaneous reduction in SAR compared to 1.5T. Images of the fetal brain obtained at 3.0T demonstrated superior tissue contrast and conspicuity compared to 1.5T.

Aims: To evaluate the differences in linear and complex heart rate dynamics in twin pairs according to fetal sex combination [male-female (MF), male-male (MM), and female-female (FF)]. Methods: Fourteen twin pairs (6 MF, 3 MM, and 5 FF) were monitored between 31 and 36.4 weeks of gestation. Twenty-six fetal heart rate (FHR) recordings of both twins were simultaneously acquired and analyzed with a system for computerized analysis of cardiotocograms. Linear and nonlinear FHR indices were calculated. Results: Overall, MM twins presented higher intrapair average in linear indices than the other pairs, whereas FF twins showed higher sympathetic-vagal balance. MF twins exhibited higher intrapair average in entropy indices and MM twins presented lower entropy values than FF twins considering the (automatically selected) threshold r Lu . MM twin pairs showed higher intrapair differences in linear heart rate indices than MF and FF twins, whereas FF twins exhibited lower intrapair differences in entropy indices. Conclusions: The results of this exploratory study suggest that twins have sex-specific differences in linear and nonlinear indices of FHR. MM twins expressed signs of a more active autonomic nervous system and MF twins showed the most active complexity control system. These results suggest that fetal sex combination should be taken into consideration when performing detailed evaluation of the FHR in twins.

Aim: Evaluate the relationship between neonatal weight and pregnancy-associated plasma protein-A. Methods: Retrospective study on 2564 singleton pregnancies with healthy term neonates in three groups of women with different values of pregnancy-associated plasma protein-A who underwent the combined test during the first trimester. Non-parametric test and correlation analysis for statistical elaboration were carried out. Results: There exists a correlation between the serum levels of pregnancy-associated plasma protein-A in the first trimester of pregnancy and neonatal weight. Values of pregnancy-associated plasma protein-A lower than the 25 th percentile are associated with neonatal weight in a significant way. There was no significant association between pregnancy-associated plasma protein-A values above 1.50 MoM and neonatal weight. Conclusion: This study confirms the positive correlation between circulating concentrations of pregnancy-associated plasma protein-A and fetal growth. Low neonatal weight and factors that can cause this could be determined from the first trimester by measuring the concentrations of pregnancy-associated plasma protein-A in maternal serum. Even if the association between the levels of pregnancy-associated plasma protein-A and a low neonatal weight has been demonstrated, however, we have to say that the sensitivity of a such screening method for the prediction of low birth weight and perinatal complications seems to be rather low. The variations of pregnancy-associated plasma protein-A during the first trimester cannot be used as a marker of excessive fetal growth.

Objective: This study aims to compare outcomes of antenatal testing in women who received testing between 40 weeks and 40+6 weeks versus those who received testing at ≥41 weeks. Materials and methods: This retrospective study included women without maternal comorbidities, who were referred for outpatient antenatal testing for gestational age ≥40 weeks. We compared women who received antenatal testing between 40 and 40+6 weeks (Group 1), to those who were only tested at ≥41 weeks (Group 2). Results: A total of 827 Group 1 and 244 Group 2 pregnancies were evaluated. One-hundred and eighty-nine (18%) were sent to labor and delivery (L&D) for further evaluation. There were no significant differences between groups in terms of being sent or admitted to labor and delivery, the reason for which women were sent, induction of labor, mode of delivery, neonatal length of stay, or admission to intensive care. Conclusion: Pregnancies tested at 40 weeks were identified as abnormal and sent to L&D at the same rate as those tested at 41 weeks. Therefore, it may be reasonable to initiate fetal surveillance at the estimated date of delivery.

Aims: Neurological outcomes differ considerably between symptomatic and asymptomatic infants with congenital cytomegalovirus (CMV) infection. Our objective was to characterize laboratory markers in symptomatic newborns in comparison with asymptomatic newborns with congenital CMV infection. Methods: Ten newborns with symptomatic and 13 newborns with asymptomatic congenital CMV infection were included in this 3-year prospective cohort study. Total immunoglobulin M (IgM), CMV-IgM, CMV antigenemia, and CMV-DNA in blood and urine were measured and their positive rates and quantitative values compared between the symptomatic and asymptomatic groups. Results: Fifty percent of newborns in the symptomatic group were positive based on total IgM; this was significantly lower than in the asymptomatic group (100%). Quantitative total IgM values were significantly lower, and there were significantly more copies of CMV-DNA in the blood of symptomatic newborns than in asymptomatic newborns (median values for total IgM: 14 vs. 43 mg/dL and blood CMV-DNA: 3.2×10 2 vs. 3.5×10 1 copies/10 6 white blood cells). CMV-IgM, CMV antigenemia, and urine CMV-DNA did not differ significantly between groups. Conclusion: Low total IgM values and high blood CMV loads were associated with the presence of symptoms in newborns with congenital CMV infection.

Objective: We aimed to investigate the clinical characteristics and postnatal outcomes of fetuses with congenital diaphragmatic hernia (CDH) and additional anomalies. Materials and methods: We reviewed the charts of fetuses with CDH managed between 2005 and 2013. Patients were divided into complex and isolated groups based on the presence of additional anomalies. We analyzed the respective polyhydramnios, liver herniation, stomach position, lung to thorax transverse area ratio (LTR), and prognoses of the two groups. The survival rates of both groups were assessed based on the LTR as well as on stomach and liver positions. Results: CDH was diagnosed in 65 fetuses, and additional anomalies were found in 23. The incidences of liver herniation, polyhydramnios, and death were significantly higher, and LTR was significantly lower, in the complex group. The mortality rate of fetuses with a LTR <0.08 was lower than that of fetuses with a LTR of ≥0.08 in the complex group. Further, the survival rate of fetuses with intrathoracic liver was lower than those without liver herniation. Conclusions: The prognosis of complex CDH is poor. This may result from both the associated anomalies and the severity of CDH itself. Even in complex CDHs, intrathoracic liver and LTR values are useful in estimating postnatal outcome.

Objective: To assess the accuracy of lipopolysaccharide binding protein (LBP) for diagnosing late-onset neonatal sepsis (LONS) in very low birth weight (VLBW) infants. Study design: Observational, prospective study. We assessed the diagnostic performance of LBP in 26 suspected LONS episodes among 54 patients. Proven and probable LONS episodes were recorded according to established criteria. Receiver operating characteristic curve analysis was performed to evaluate LBP’s ability to predict LONS. Results: LONS was diagnosed in 17 of 26 episodes. LBP levels were significantly higher in confirmed LONS episodes (P<0.001). The area under the curve of LBP was 0.89. A cut-off of 17.5 μg/mL had a sensitivity of 94.1%, a specificity of 77.8%, a positive predictive value of 88.9% and a negative predictive value of 87.5%. Conclusions: Serum LBP measurement may be useful as an additional tool in the evaluation of suspected LONS in VLBW infants.

Aims: To test if there is a stepwise difference in neonatal outcomes according to the stage (or grade) of histological inflammatory response in the chorioamniotic membranes and umbilical cords of preterm premature rupture of membranes (PPROM). Method: This retrospective study included singleton pregnancies diagnosed as PPROM and delivered prior to 34 weeks of gestation (n=339). Acute histological chorioamnionitis and funisitis were subdivided into stages (or grade) as defined by Redline et al. Neonatal composite morbidities and mortality were also monitored. Univariate and multivariate analyses were conducted. Results: Increasing stage (or grade) of acute histological chorioamnionitis and funisitis was significantly associated with an earlier gestational age at membrane rupture and delivery. Among neonatal outcomes, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage, retinopathy of prematurity, and composite morbidity showed incremental incidence according to increased stage (or grade) of acute chorioamnionitis, while periventricular leukomalacia and necrotizing enterocolitis did not. Only RDS, BPD, and composite morbidity showed similar incremental incidences associated with severity of funisitis stage. However, the incremental trends of each neonatal outcome were found to be nonsignificant by multivariate analysis adjusting confounding variables including gestational age at delivery. Conclusion: Higher incidences of neonatal morbidity according to increased stage (or grade) of either acute histological chorioamnionitis or funisitis were due to an earlier gestational age at delivery.

The value of testing for inherited thrombophilia in pregnancy has been debated in literature with regard to its utility in preventing adverse obstetrical outcomes or identifying women at risk for it. In this commentary, an evidence based approach is used to investigate the strength of association between thrombophilias and recurrent pregnancy loss and stillbirth. Several studies and meta-analyses have shown that there is only a weak association with recurrent pregnancy loss. However, many of these studies were underpowered, and there was significant heterogeneity-issues that are addressed in this paper. The evidence for association with stillbirth is lacking, but the few studies that are available seem to suggest a stronger correlation than for recurrent pregnancy loss. Further, the benefit of treating thrombophilias with anticoagulation in order to prevent these outcomes is discussed. While there is a lack of evidence looking at whether anticoagulation prevents stillbirth, there is strong evidence to show that anticoagulation does not prevent recurrent pregnancy loss. Finally, guidelines put out by various obstetrical and hematological societies regarding this topic are summarized.