Volume 45, Issue 5

Mycoplasmata have been linked to pregnancy complications and neonatal risk. While formerly a limited number of species could be discovered by cultures, molecular biology nowadays discovers both lower quantities and more diverse species, making us realize that mycoplasmata are ubiquitous in the vaginal milieu and do not always pose a danger for pregnant women. As the meaning of mycoplasmata in pregnancy is not clear to many clinicians, we summarized the current knowledge about the meaning of different kinds of mycoplasmata in pregnancy and discuss the potential benefits and disadvantages of treatment. Currently, there is no general rule to screen and treat for mycoplasmata in pregnancy. New techniques seem to indicate that Ureaplasma parvum (Up) , which now can be distinguished from U. urealyticum (Uu) , may pose an increased risk for preterm birth and bronchopulmonary disease in the preterm neonate. Mycoplasma hominis (Mh) is related to early miscarriages and midtrimester abortions, especially in the presence of abnormal vaginal flora . Mycoplasma genitalium (Mg) is now recognized as a sexually transmitted infection (STI) that is involved in the causation of cervicitis, pelvic inflammatory disease (PID) in non-pregnant, and preterm birth and miscarriages in pregnant women, irrespective of the presence of concurrent other STIs, like Chlamydia or gonorrhoea. Proper studies to test for efficacy and improved pregnancy outcome are scarce and inconclusive. Azythromycin is the standard treatment now, although, for Mg , this may not be sufficient. The role of clarithromycin in clinical practice still has to be established. There is a stringent need for new studies based on molecular diagnostic techniques and randomized treatment protocols with promising and safe antimicrobials.

Rates of cesarean sections have been on the rise over the past three decades all over the world, despite the ideal rate of 10–15% that had been set by the World Health Organization (WHO) in 1985, in Fortaleza, Brazil. This epidemic increase in the rate of cesarean delivery is due to many factors which include, cesarean delivery on request, advanced maternal age at first pregnancy, decrease in number of patients who are willing to try vaginal birth after cesarean delivery, virtual disappearance of vaginal breech delivery, perceived increase in the weight of the fetus and increase in the number of women with chronic medical conditions such as Diabetes Mellitus and congenital heart disease in the reproductive age. There is no doubt that cesarean delivery is a safe procedure and it is getting safer and safer for many reasons. However, like all other surgical procedures it is not without risks both to the mother and the new born. There is a substantial increase in the incidence of morbidly adherent placenta and the risk of scar pregnancy. In the Middle East and many African and Asian countries women tend to have large families. The number of previous cesarean section deliveries is directly proportional to the risk of developing morbidly adherent placenta. Morbidly adherent placenta is the most common cause of emergency postpartum hysterectomy, which is often associated with multiple surgical complications, severe maternal morbidity and mortality. The increased rates of cesarean sections lead to increased rates of scar pregnancies, which can have lethal consequences. Cesarean delivery has a negative impact on the infant immune system. This effect on the infant led to the introduction of a new concept called “Vaginal seeding”. This refers to the practice of transferring some maternal vaginal fluid to the infant born via cesarean section in an effort to enhance its immune system.

Objectives: 1) To characterize the cellular composition of the amniotic fluid of patients diagnosed with clinical chorioamnionitis at term, as a function of the presence or absence of microorganisms determined by cultivation techniques, and 2) to characterize the cytokine production by white blood cells present in the amniotic fluid using flow cytometry-based techniques. Materials and methods: Amniotic fluid samples from 20 women who had the diagnosis of clinical chorioamnionitis at term were analyzed using cultivation techniques (for aerobic and anaerobic bacteria as well as genital Mycoplasmas). Amniotic fluid IL-6 concentrations were determined by an enzyme-linked immunosorbent assay. Amniotic fluid leukocytes were visualized by using hematoxylin and eosin staining and immunofluorescence. Immunophenotyping of surface markers and cytokines was performed in amniotic fluid leukocytes using flow cytometry. Results: 1) Neutrophils (CD45+CD15+ cells) were the most common leukocyte subset found in the amniotic fluid, followed by monocytes (CD45+CD14+ cells); other white blood cells (such as lymphocytes and natural killer cells) were scarce in the amniotic fluid; 2) the absolute counts of neutrophils and monocytes were significantly higher in patients with microorganisms found in the amniotic fluid than in those without detectable microorganisms, using cultivation techniques; 3) there was a significant correlation between the absolute counts of neutrophils and monocytes determined by flow cytometry (Spearman’s correlation=0.97; P<0.001); 4) there was a significant correlation between the absolute white blood cell count determined with a hemocytometer chamber and by flow cytometric analysis (Spearman’s correlation=0.88; P<0.001); and 5) the profile of cytokine expression differed between monocytes and neutrophils; while neutrophils predominantly produced TNF-α and MIP-1β, monocytes expressed higher levels of IL-1β and IL-1α. Conclusion: Flow cytometry analysis of the amniotic fluid of patients with intra-amniotic infection and clinical chorioamnionitis at term demonstrated that neutrophils and monocytes are the most common cells participating in the inflammatory process. We have characterized, for the first time, the differential cytokine expression by these cells in this important complication of pregnancy.

Objective: Clinical chorioamnionitis is the most common infection/inflammatory process diagnosed in labor and delivery units worldwide. The condition is a syndrome that can be caused by (1) intra-amniotic infection, (2) intra-amniotic inflammation without demonstrable microorganisms (i.e. sterile intra-amniotic inflammation), and (3) maternal systemic inflammation that is not associated with intra-amniotic inflammation. The presence of intra-amniotic inflammation is a risk factor for adverse maternal and neonatal outcomes in a broad range of obstetrical syndromes that includes clinical chorioamnionitis at term. Although the diagnosis of intra-amniotic infection has relied on culture results, such information is not immediately available for patient management. Therefore, the diagnosis of intra-amniotic inflammation could be helpful as a proxy for intra-amniotic infection, while results of microbiologic studies are pending. A rapid test is now available for the diagnosis of intra-amniotic inflammation, based on the determination of neutrophil collagenase or matrix metalloproteinase-8 (MMP-8). The objectives of this study were (1) to evaluate the diagnostic indices of a rapid MMP-8 test for the identification of intra-amniotic inflammation/infection in patients with the diagnosis of clinical chorioamnionitis at term, and (2) to compare the diagnostic performance of a rapid MMP-8 test to that of a conventional enzyme-linked immunosorbent assay (ELISA) interleukin (IL)-6 test for patients with clinical chorioamnionitis at term. Materials and methods: A retrospective cohort study was conducted. A transabdominal amniocentesis was performed in patients with clinical chorioamnionitis at term (n=44). Amniotic fluid was analyzed using cultivation techniques (for aerobic and anaerobic bacteria as well as genital Mycoplasmas) and broad-range polymerase chain reaction (PCR) coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). Amniotic fluid IL-6 concentrations were determined by ELISA, and rapid MMP-8 results were determined by Yoon’s MMP-8 Check ® . Intra-amniotic inflammation was defined as an elevated amniotic fluid IL-6 concentration ≥2.6 ng/mL, and intra-amniotic infection was diagnosed by the presence of microorganisms in the amniotic fluid accompanied by intra-amniotic inflammation. The diagnostic indices of Yoon’s MMP-8 Check ® for the identification of intra-amniotic inflammation were calculated. In order to objectively compare Yoon’s MMP-8 Check ® with the ELISA IL-6 test for the identification of intra-amniotic inflammation, we used an amniotic fluid white blood cell (WBC) count ≥50 cells/mm 3 to define intra-amniotic inflammation. Results: (1) A positive rapid MMP-8 test had a sensitivity of 82.4% (28/34), specificity of 90% (9/10), positive predictive value of 96.6% (28/29), negative predictive value of 60% (9/15), positive likelihood ratio 8.2 (95% CI 1.3–53.2), and negative likelihood ratio 0.2 (95% CI 0.1–0.4) for the identification of intra-amniotic inflammation (prevalence 77.3%); (2) a positive rapid MMP-8 test had a sensitivity of 91.7% (22/24), specificity of 65% (13/20), positive predictive value of 75.9% (22/29), negative predictive value of 86.7% (13/15), positive likelihood ratio of 2.6 (95% CI 1.4–4.8), and negative likelihood ratio of 0.1 (95% CI 0.03–0.5) for the identification of intra-amniotic infection; (3) the rapid MMP-8 test had a significantly higher specificity than the ELISA IL-6 test in the identification of intra-amniotic inflammation as determined by an amniotic fluid WBC count ≥50 cells/mm 3 . The sensitivity and accuracy of the rapid MMP-8 test were comparable to those of the ELISA IL-6 test; and (4) importantly, the rapid MMP-8 test had 100% sensitivity and 100% negative predictive value in the identification of neonates affected with fetal inflammatory response syndrome (FIRS). Conclusion: The rapid diagnosis of intra-amniotic inflammation is possible by analysis of amniotic fluid using a point-of-care test for MMP-8. Patients with a positive test are at risk of delivering a neonate affected with systemic inflammation, a risk factor for adverse neonatal outcome.

In obstetric practice, each pregnant woman presents with a composite of maternal and fetal characteristics that can alter the risk of significant harm without cesarean intervention. The hospital’s availability of resources and the obstetrician’s training, experience, and skill level can also alter the risk of significant harm without cesarean intervention. This paper proposes a clinical ethical framework that takes these clinical and organizational factors into account, to promote a deliberative rather than simplistic approach to decision-making and counseling about cesarean delivery. The result is a clinical ethical framework that should guide the obstetrician in fine-tuning his or her evidence-based, beneficence-based analysis of specific clinical and organizational factors that can affect the strength of the beneficence-based clinical judgment about cesarean delivery. We illustrate the clinical application of this framework for three common obstetric conditions: Category II fetal heart rate tracing, prior non-classical cesarean delivery, and breech presentation.

Objective: To compare translabial three-dimensional (3D) power Doppler ultrasound with Bishop score and transvaginal ultrasound measurements for cervical assessment before induction of labor with dinoprostone or cervical ripening balloon. Materials and methods: Translabial cervical volume and length, vascularization indices and transvaginal cervical length were measured. Results were compared among women who had vaginal delivery at 24 h or less and more than 24 h after the insertion of the dinoprostone vaginal insert or cervical ripening balloon and among women who had vaginal delivery and cesarean delivery for failure to go into labor or failure to progress. Results: There was no correlation between the time to delivery after a ripening agent was applied and translabial cervical volume, translabial cervical length, vascularization index (VI), flow index (FI), vascularization flow index (VFI), transvaginal cervical length and Bishop scores. The ultrasonographic measurements were no different among women who had vaginal delivery at 24 h or less and more than 24 h and among women who had vaginal delivery and cesarean delivery for failure to go into labor or failure to progress. Conclusion: In this study, we failed to demonstrate the superiority of translabial 3D ultrasonography over Bishop score and transvaginal ultrasonography for predicting the success of induction of labor.

Objective: Umbilical cord prolapse occurs when the cord prolapses ahead of or alongside the presenting part. It is an acute obstetric emergency with potential catastrophic effects. We set out to assess incidence of cord prolapse, as well as rates and characteristics of perinatal death associated with the condition. Study design: This was a retrospective cohort study. All recorded cases of cord prolapse were included, and rates of perinatal death and encephalopathy, as well as intrapartum and maternal characteristics were examined. Results: There were 156,130 deliveries at the hospital over the 20-year study period. Three hundred and seven cases of cord prolapse were identified (1.9/1000 deliveries). There was a decrease in the incidence of cord prolapse over the course of the study. The rate peaked in 1999 at 3.9/1000 and was just 0.8/1000 of all deliveries in 2007. The majority of cases (216/307, 70%) occurred in multiparas; however, nulliparous parturients were more likely to have a perinatal death [12% (11/91) vs. 4.6% (10/216)]. The rate of perinatal death in cases of cord prolapse was 6.8% (21/307). Over half of perinatal deaths (11/21) occurred in infants of mothers who presented with ruptured membranes, seven of these infants were already dead on reaching hospital. There was just one case of neonatal encephalopathy associated with cord prolapse, giving an incidence of 0.32%. Conclusion: Cord prolapse carries a significant risk of perinatal death, approximately 7%. The corresponding rate of encephalopathy is low. A significant number of deaths were diagnosed on presentation to hospital and were not deemed preventable.

Objective: YKL-40 is a secreted glycoprotein and has been implicated in the proliferation and differentiation of malignant cells, extracellular tissue remodelling, neovascularisation, inhibition of cancer cell apoptosis and stimulation of tumour-associated fibroblasts. The purpose of this study was to evaluate YKL-40 tissue expression in extravillous trophoblast invasion and its possible implication in placenta creta. Methods: A total of 35 placenta creta cases and six control cases were included in the study, of which eight cases were placenta accreta, 12 were increta and 15 were percreta. Histological YKL-40 staining was scored in tissue as weak (1), medium (2) and strong (3). Results: YKL-40 immunoreactivity intensity in the percreta group was significantly higher compared to the increta and accreta groups (2.47±0.74, 1.33±0.49 and 1.37±0.52, respectively; P=0.000). YKL-40 immunoreactivity intensity was positively correlated with creta (r=0.6; P=0.000), depth of invasion (r=0.49; P=0.003) and depth of invasion to full thickness ratio (r=0.58; P=0.000). Conclusion: This study demonstrated that YKL-40 is strongly expressed in placenta percreta and is correlated with extravillous trophoblast invasion. These findings may be informative for understanding the pathophysiology of placenta creta.

Objective: To evaluate B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac structure and function in normal women through pregnancy and the postpartum. Methods: In this prospective observational study, we obtained serial transthoracic echocardiograms, BNP, and NT-proBNP at seven intervals from 6 weeks’ gestation through 12 months postpartum. Women with hypertension or cardiac disease were excluded. Using 6–12 months postpartum as reference for non-pregnant levels, echocardiogram measurements and BNP/NT-proBNP were compared over time using linear mixed models with Tukey-Kramer adjustment for multiple comparisons. Results: Of 116 patients, data was available for 78–114 healthy pregnant or postpartum women within each time interval, and 102 patients provided data for ≥4 intervals. Compared to 6–12 months postpartum, BNP and NT-proBNP remained stable through pregnancy and delivery, increased within 48 h postpartum (P<0.0001), then returned to baseline. Left ventricular volume increased within 48 h postpartum (P=0.021) while left atrial volume increased at 18–24 weeks (P=0.0002), 30–36 weeks (P<0.0001) and within 48 h postpartum (P=0.002). The transmitral early/late diastolic velocity (E/A) ratio, transmitral early/peak mitral annulus diastolic velocity (E/E′) ratio, isovolumic relaxation times, and mitral valve deceleration times were similar within 48 h and 6–12 months postpartum. Conclusion: In normal women, BNP/NT-proBNP, left atrial, and left ventricular volumes increase within 48 h postpartum without indications of altered diastolic function.

Background: Not much data are available on the natural history of bilateral renal agenesis, as the medical community does not typically offer aggressive obstetric or neonatal care asbilateral renal agenesis has been accepted as a lethal condition. Aim: To provide an evidence-based, ethically justified approach to counseling pregnant women about the obstetric management of bilateral renal agenesis. Study design: A systematic literature search was performed using multiple databases. We deploy an ethical analysis of the results of the literature search on the basis of the professional responsibility model of obstetric ethics. Results: Eighteen articles met the inclusion criteria for review. With the exception of a single case study using serial amnioinfusion, there has been no other case of survival following dialysis and transplantation documented. Liveborn babies die during the neonatal period. Counseling pregnant women about management of pregnancies complicated by bilateral renal agenesis should be guided by beneficence-based judgment informed by evidence about outcomes. Conclusions: Based on the ethical analysis of the results from this review, without experimental obstetric intervention, neonatal mortality rates will continue to be 100%. Serial amnioinfusion therefore should not be offered as treatment, but only as approved innovation or research.

Aim: The aim of our study was to assess fetal thymus size in diabetic pregnancies compared with normal pregnancies. Methods: Sonographic fetal thymus size was retrospectively assessed in 161 pregnancies with maternal diabetes and in 161 uncomplicated pregnancies matched by gestational age. The anteroposterior thymic and the intrathoracic mediastinal diameter were measured and the quotient was calculated [thymic-thoracic ratio (TT-ratio)]. In addition, we defined the quotient of the anteroposterior thymic diameter and the head circumference as thymus-head ratio (TH-ratio). The maternal diabetes cases were subdivided into three groups: (1) diet-controlled gestational diabetes, (2) insulin-dependent gestational diabetes and (3) preexisting maternal diabetes. Results: TT-ratio and TH-ratio were smaller in pregnancies with maternal diabetes (P<0.001 and P<0.001, respectively). In all three maternal diabetes subgroups, the TT-ratio and the TH-ratio were lower compared with the control group (P<0.001 for each group). Conclusions: Reduced fetal thymus size seems to be associated with diabetic pregnancy. We introduce fetal thymus size as a new potential prognostic parameter for maternal diabetes.

Objective: Our purpose was to examine the association between discordant growth and perinatal mortality and morbidity among twins with careful adjustment for maternal confounding factors. Study design: Two cohorts with and without chorionicity data were compared using generalized estimating modeling. Results: Our population-based dataset consisted of 12,656 individual twins from whom 4% (452/12,656) had≥30% growth discordance. A subgroup of this population with chorionicity information had an incidence of 7.3%≥30% growth discordance. In growth-discordant twins, perinatal mortality and morbidity were higher than concordant pairs (P<0.01). Low Apgar score and perinatal mortality were more frequent in growth-discordant twins compared with growth-concordant ones (all P<0.01). Conclusion: Birth weight discordance (BWD) places twins at increased risk of perinatal mortality. Growth discordance was also an independent risk factor for lower Apgar score of 5 min less than 5.

Background: Neonatal hyperbilirubinemia is influenced by a wide variety of factors, one of which is hemolysis. Serious hyperbilirubinemia may lead to a kernicterus with detrimental neurologic sequelae. Patients suffering from hemolytic disease have a higher risk of developing kernicterus. Carbon monoxide (CO), a byproduct of hemolysis or heme degradation, was described by Sjöstrand in the 1960s. It is transported as carboxyhemoglobin (COHb) and exhaled through the lungs. We were interested in a potential correlation between COHb and total serum bilirubin (TSB) and the time course of both parameters. Materials and methods: We used a point of care (POC) blood gas analyzer and did a retrospective analysis of bilirubin and COHb data collected over a 60-day period. Results: An arbitrary cut-off point set at 2% COHb identified four patients with hemolytic disease of different origins who required phototherapy. In one patient with atypical hemolytic uremic syndrome (aHUS), COHb preceded the rise in bilirubin by about 2 days. Despite this displacement, there was a moderately good correlation of COHb with TSB levels <15 mg/dL (257 μmol/L) (r 2 : 0.80) and direct bilirubin (r 2 : 0.78) in the first patient. For all the four patients and all time points the correlation was slightly lower (r 2 : 0.59). Conclusions: COHb might be useful as a marker for high hemoglobin turnover to allow an earlier identification of newborns at risk to a rapid rise in bilirubin.

Aim: To compare the growth attainment of preterm children and their cardiovascular risk factors at adolescence with the values measured in term children in Germany. Methods: About 17,641 children aged 0 to <18 years were studied between 2003 and 2006 in the population representative German KiGGS survey (“German Health Interview and Examination Survey for Children and Adolescents”) using questionnaires, physical examinations, standardized anthropometric and blood pressure measurements, and blood sample analyses. Analysis of covariance (ANCOVA) was employed for the analyses of anthropometric parameters. Results: About 11.8% of the 16,737 children with complete and valid data had been born preterm. After adjustment for covariates the estimated z-scores over the total age range were larger in term compared to preterm children for length/height (P<0.001; estimated difference B=0.277, 95% CI 0.191–0.362), head circumference (P<0.001; B=0.238, 95% CI 0.144–0.333), BMI (P=0.001; B=0.160, 95% CI 0.069–0.252), and skinfold thickness (P=0.220; B=0.058, 95% CI −0.035 to 0.151). The onset of pubertal development was slightly (but not significantly) earlier in term compared to preterm children. At 14 to <18 years, anthropometric and biochemical indicators of cardiovascular diseases were not worse in preterm compared to term children. Conclusions: Preterm-born German adolescents remained significantly shorter, lighter, and had a smaller head circumference than term-born adolescents, but the risk indicators for cardiovascular diseases were not higher.

Aim: To evaluate risk factors for pulmonary hemorrhage (PH) in extremely low birth weight infants (ELBW) taking into consideration coagulation screens, platelet counts, transfusion of fresh frozen plasma (FFP), and platelet concentrates prior to PH. Patients and methods: A retrospective case-control study consisting of 20 ELBW infants with PH and 40 matched controls. Coagulation screens, platelet counts at birth and at onset of PH, and transfusion frequencies prior to PH were compared to case-controls at birth and 24–96 h after birth. Results: While the initial platelet counts, fibrinogen concentrations, and international normalized ratios were similar in PH infants and controls, the activated partial prothrombin time was prolonged (P=0.05). Compared to 28% of case controls (P<0.05), 55% of infants with later PH received FFP prior to PH. Platelet counts were significantly lower at onset of PH (median 81/nL; range: 37–236/nL) compared to controls (166/nL; 27–460/nL; P<0.005). Multivariate analysis indicated a lack of antenatal steroids, supplemental oxygen, and transfusion of FFP as independent risk factors for PH. Conclusion: Prolonged activated partial thromboplastin time (aPTT) might be associated with PH. PH does not primarily depend upon severe thrombocytopenia. A developmental mismatch in hemostasis by transfusion of adult donor plasma should be considered a risk factor for PH.