Volume 33, Issue 6

It has become clear in recent years that apoptosis is a normal process in trophoblast turnover during pregnancy. Increased trophoblast apoptosis has been observed in the placenta of women with preeclampsia, serum from women with preeclampsia has been found to induce increased trophoblast sensitivity to Fas-mediated apoptosis, and serum from women with preeclampsia has elevated levels of various chemokines, growth factors and cytokines that are involved in the regulation of apoptosis. This review highlights the importance of apoptosis in normal placental development and explores the mechanisms whereby Fas-mediated apoptosis may play a role in conditions related to abnormal placentation, such as preeclampsia.

The development of the human central nervous system (CNS) begins in the early embryonic period and proceeds through a sequence of very complicated processes long after delivery. Although the neurodevelopmental processes are genetically determined, their complexity and intensity implicates the vulnerability of the CNS to number of environmental factors. There is substantial evidence to show that many neurological problems, from minor cerebral dysfunction to the cerebral palsy, originate form the prenatal, rather than perinatal or postnatal periods of life. A variety of neurological and neuropsychiatric diseases is nowadays considered to originate, at least partly, from the prenatal incidents. In most of these conditions, there is no reliable parameter for detection or prediction of cerebral lesions and there is an urgent need to develop strategies that would enable the early detection of cerebral lesions or indications that such lesions might occur. The new, advanced, imaging techniques such as 3-dimensional and 4-dimensional sonography, opened a new perspective for the investigation of structural and functional development of fetal CNS. The application of these techniques might improve our understanding of the prenatal neurodevelopmental events and possibly facilitate the development of diagnostic strategies for early detection or prevention of brain dysfunctions and damage.

Labor induction is used in approximately 20% of pregnancies in Europe and North America. Prostaglandins and prostaglandin analogs are favored when women undergoing labor induction have an unripe cervix. Controlled-release dinoprostone, delivered over 24 h from a vaginal insert, results in cervical ripening within 12 h in most women. It is marginally more effective than immediate release formulations and has similar efficacy to misoprostol, a prostaglandin E 1 analog used off-label for this indication. The controlled-release preparation offers many advantages compared with an immediate-release formulation: a single application is sufficient; it is less invasive; it is easily administered and removed, allowing greater dose control. The most significant adverse effect, uterine hyperstimulation, with and without an effect on fetal heart rate, occurs in 5–15% of patients, which is comparable with other formulations or misoprostol. The insert can be removed easily on the first sign of uterine hyperstimulation, or as soon as labor starts. The efficacy and safety of controlled-release dinoprostone are comparable whether it is used in the outpatient or the inpatient setting. For low-risk women, outpatient use may be a highly attractive option, potentially reducing hospital costs, and improving patient convenience. The ease of use of controlled-release dinoprostone and women's satisfaction emphasize its benefits over many other agents used to ripen the cervix.

Maternal nutrition may be one of the most important under-evaluated factors contributing to the contemporary rise in prematurity in the United States and other industrialized nations around the world. Slowed fetal growth has been repeatedly shown to be associated with preterm birth, in both singleton and twin pregnancies. Antecedents of impaired fetal growth include a wide variety of factors, including intergenerational effects, biological and social factors related to race and ethnicity, maternal pregravid weight and gestational weight gain, and iron and mineral status. An assessment of maternal nutritional status, including anthropometric factors, is an integral component of effective prenatal care, and may facilitate a reduction in prematurity.

Objective: Hydroxyprogesterone caproate (17-P) and progesterone have been shown to decrease the rate of preterm birth in high-risk pregnant women, but the mechanism of action is unknown. We hypothesized that 17-P or progesterone would reduce production of the pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α), after lipopolysaccharide (LPS) stimulation of whole blood. Study design: Whole blood collected from 10 non-pregnant women in the follicular phase was treated with LPS (1000 ng/mL) alone or with either 17-P or progesterone (125 ng/mL and 1250 ng/mL) and LPS. Supernatant collected after 24 h was tested for TNF-α by enzyme immunoassay. Results were compared using the Wilcoxon rank sum test. Results: Whole blood treated with 17-P or progesterone in addition to LPS produced significantly higher TNF-α concentrations than blood treated with LPS alone. Conclusion: 17-P and progesterone appear to have a pro-inflammatory effect during LPS stimulation of blood from non-pregnant women in vitro . Our data suggest that the reduction in pre-term birth in women treated with progesterone is not mediated through an anti-inflammatory effect on peripheral blood cells.

Aim: To determine the effect of routine intraoperative cervical dilatation during elective cesarean section on maternal morbidity. Subjects and methods: Patients with even numbers in the operative elective cesarean section list were included in the study. Of these, every second patient underwent intraoperative cervical dilatation. All participants in the two groups had otherwise similar preoperative care, operative procedures and subsequent clinical care. Blood loss was estimated and maternal infection status was assessed postoperatively by any rise of temperature or wound infection. Results: Of the 131 patients included in the study, 67 underwent cervical dilation and 64 served as controls. There was no significant difference in postoperative hemoglobin, incidence of fever, or wound infection between the two groups. Only two of the cervical dilation group and one control patient developed postoperative fever. A hemoglobin drop of more than 0.5 g/dL was noted in 27 and 26 patients in the cervical dilation and the no dilation groups, respectively (NS). None of the study patients had signs of wound infection. Conclusion: Intraoperative cervical dilatation during elective cesarean section did not reduce the risk of postoperative maternal fever, wound infection or change in hemoglobin concentration.

Background: Transient hypothyroxinaemia of prematurity (THOP) is a common condition of preterm infants whose causes remain unclear. We tested the hypothesis that THOP is associated with histological chorioamnionitis (HCA). Methods: Whole blood T 4 and TSH concentrations on day 4 and at 40 weeks' postmenstrual age (rtx-T4 and rtx-TSH), placental histology and illness severity were prospectively evaluated in 155 very low birth weight (VLBW) infants. Results: HCA-positive infants showed significantly decreased blood total T 4 concentrations on day 4, as compared to the HCA-negative population (P<0.0001), along with comparable TSH, rtx-T 4 , and rtx-TSH blood concentrations. None of the infants showed evidence of hypothyroidism during the study. A total T 4 ≤4.4 μg/dL on postnatal day 4 identified HCA-positive newborns with 90.8%, sensitivity, 94.7%, specificity, 96.7% positive predictive and 85.7% negative predictive values. HCA (OR: 32.19; 95% CI: 8.95–115.64), birth weight ≤880 g (OR: 4.1; 1.15–14.64), and RDS (OR: 3.71, 95% CI: 1.13–12.25) were independently associated with evidence of hypothyroxinaemia on day 4. Conclusion: Our findings indicate a previously un-recognized relationship between HCA and THOP, hence suggesting a predominant role for a fetal systemic inflammatory response syndrome in the pathogenesis of THOP.

Objective : To compare neonatal results from patients with gestational diabetes mellitus (GDM) who were treated with insulin, glyburide and acarbose. Results : Seventy patients diagnosed with GDM who needed therapy to complement diet and physical activities were included in the study. One group was assigned to insulin therapy (n=27), a second group was assigned to glyburide therapy (n=24) and a third group was assigned to acarbose therapy (n=19). Maternal characteristics were similar in the three groups. Glucose control was not achieved in five (20.8%) of the patients using glyburide and in eight (42.1%) of patients using acarbose. No statistical difference was observed in fasting and post-prandial glucose levels or in average newborn weight in the three groups. The rate of large for gestational age (LGA) fetuses was 3.7, 25 and 10.5% in the groups treated with insulin, glyburide and acarbose, respectively. Neonatal hypoglycemia was observed in eight newborns, six of which from the glyburide group. Conclusion : We believe that glyburide and acarbose can be promising alternative therapies for the treatment of GDM. Glyburide controlled glucose levels in most patients and it was more efficient than acarbose. Glyburide showed a higher rate of macrosomia and neonatal hypoglycemia as compared to other therapies.

Objective: To compare women with spontaneous preterm delivery before 37 weeks and women who delivered at term with respect to amniotic fluid C-reactive protein (CRP), glucose levels, and white blood cell counts at the time of genetic amniocentesis. Study design: The study was conducted on 216 pregnant women who underwent genetic amniocentesis between the 15 th and 18 th weeks of gestation at Baskent University Obstetrics and Gynecology Department. All patients were followed until delivery for the occurrence of pregnancy complication. Indications for amniocentesis included abnormal triple test results showing increased risk for Down's syndrome, advanced maternal age and sonographic findings indicative for chromosomal abnormalities. The samples were carried immediately to the laboratory for cytogenetic and biochemical examination. Women with spontaneous preterm delivery before 37 weeks (n=20) and those who delivered at term (n=196) were compared with respect to some maternal and infant characteristics, amniotic fluid C-reactive protein, glucose levels, and amniotic fluid white blood cell counts. Results: During the study period 244 patients underwent amniocentesis. A chromosomal abnormality was present in 11 patients. 1 patient had a spontaneous pregnancy loss within 3 weeks after the procedure and 16 patients were delivered for fetal or maternal indications (preeclampsia, fetal growth restriction, placenta previa). The remaining 216 women were included in the study and investigated for the risk of preterm delivery. The prevalence of spontaneous preterm delivery before 37 weeks was 9.3% (20/216). There were no significant differences between the preterm delivery and the term delivery groups with respect to C-reactive protein levels and white blood cell counts. Mean amniotic glucose levels were significantly lower in the preterm delivery group (P<0.05). Amniotic fluid glucose levels of ≤46 mg/dL had a sensitivity of 100% and NPV of 100%. Conclusion: Amniotic fluid glucose levels at the time of genetic amniocentesis are lower in women with spontaneous preterm delivery before 37 weeks compared to those who delivered at term. Amniotic fluid glucose levels of ≤46 mg/dL at the time of genetic amniocentesis may be more sensitive, cheaper and have higher negative predictive value than C-reactive protein levels and white blood cell counts for the prediction of patients in spontaneous preterm labor. The greatest benefit of amniotic fluid glucose testing might be when the physician judges the patient to be at low risk for preterm delivery.

Objective: To review our experience with a minimally invasive technique for umbilical cord occlusion as a method of selective feticide in monochorionic sets. Study design: Umbilical cord occlusion was completed using 3 mm bipolar cautery under ultrasound guidance (3D/4D, n=6; 2D, n=6) with pre and post ligation endoscopic evaluation. Results: 12 cases of monochorionic sets where selective feticide was performed were identified during the period 2000 to present. There were four triplet and eight twin gestations in the study cohort. Median interval from intervention to delivery was 16 weeks (range, 5–19). All co-twins survived the procedure and 15 of 16 were delivered after 33 weeks. Conclusions: Umbilical cord occlusion in monochorionic sets can be accomplished in a minimally invasive manner with combined endoscopic and ultrasound guidance in both twin and triplet pregnancies.

To investigate whether vascular reactivity of the umbilical artery influences differences in Doppler waveform depending on the sampling site along the cord, we studied a regional difference of endothelium-dependent vascular contractility in human umbilical artery using mechanical responses to the quick stretch of vascular smooth muscle strips. The umbilical artery resistance index (RI) values for the fetal end were significantly higher than those for the placental end. In endothelium-intact strips, stretch-induced contraction of the umbilical artery appears to decrease from the fetal to the placental end of the umbilical artery. No significant differences were noted between strips from the two locations when endothelial cells were rubbed, indicating that this regional difference is related to endothelial cell function. Indo-methacin decreased the stretch-induced contraction of endothelium-intact strips, but tetrodotoxin did not affect this association, suggesting that arachidonic acid metabolism via the cyclooxygenase pathway contributes to modulation of human umbilical artery responsiveness to stretch. These findings suggest that the difference in Doppler waveform of the umbilical artery depending on the sampling site is related to differences in vascular resistance that result from endothelium-related function.

Objective: While an echogenic intracardiac focus (EIF) is associated with an increased risk of trisomy 21 (T21), the magnitude of that risk remains controversial, particularly in the setting of a low-risk triple screen (TS). The objective of this study is to define the risk of T21 in patients with a low-risk TS and an isolated EIF. Study design: A retrospective analysis was performed on patients presenting prior to 22 6/7 weeks of gestation. Patients met criteria for inclusion if an EIF was noted, a TS had been drawn, the anatomic survey was complete and was determined to be normal, and karyotyping or delivery occurred at Bellevue Hospital. A high-risk TS was defined as a risk of <1:500, assuming a 2-fold increased risk in the setting of an isolated EIF. A low-risk TS was defined as a risk of >1:500. Statistical analysis was performed using chi-square, with p values of <0.05 considered significant. Results: 7,318 anatomic surveys were performed. An EIF was identified in 584 patients (7.98%), of which 391 met the criteria for inclusion. Of the 391, 51% were Asian and 38% were Hispanic; 348 had a low-risk TS and 43 had a high-risk TS. Patients with an EIF and a low-risk TS had a significantly lower risk of having a T21 pregnancy compared to those with a high-risk TS and an EIF (0 vs. 2.3%; p=0.004). Conclusion : An isolated EIF with a low risk TS is not associated with an increased risk of T21.

Status and school achievement of 129 children born in Hessen between 1988 and 1992 and notified by a repeatedly elevated concentration of TSH in neonatal screening were evaluated. Interviews of mothers, teachers and pediatricians were used to score the developmentand educational achievements, respectively. A total of 298,175 newborns were screened and the incidenceof permanent congenital hypothyroidism (PCH) was 1: 3,313 (n=90). The female/male ratio was 1.37:1. In the 69 PCH cases with complete data, athyreosis (52%), hypoplasia (32%), dyshormogenesis (9%) and ectopia (7%) were identified as etiologies. The mean age at start of therapy decreases from day 15 in 1988 to day 9 in 1992; however, 27% of PCH children showed reduced psychomotor development as scored by their pediatrician and 11% attended a special school for educationally subnormal children. Approximately 25% of the children had lower educational achievements irrespective of the school type. Our finding of a relatively high percentage of PCH children with subnormal development points to a failure in disease management. A follow-up program including repeated serum TSH monitoring and yearly examinations by pediatric endocrinologists and supervision by the regional screening center is necessary to ensure the long-term efficacy of neonatal screening for congenital hypothyroidism.

The purpose of this study was to assess cardiac function of newborns with mild asphyxia by a Doppler-derived index combining systolic and diastolic performance (Tei index). We studied 20 preterm infants with mild asphyxia. A control group consisted of 20 gestational age-matched preterm infants without asphyxia. Echocardiograms were performed during the fourth and seventh days after birth. Peak velocities of an early filling wave (E) and an atrial contraction wave (A) were measured from the mitral inflow velocity profile and the ratio of peak E to A was calculated. Ejection time was measured from the left ventricular outflow Doppler signal. The sum of isovolumetric times was obtained by subtracting the ejection time from the interval between cessation and onset of mitral inflow. The index was the sum of isovolumetric times divided by ejection time. Ejection fraction was also calculated. The ratio of peak E to A and ejection fraction were the same in both groups. The myocardial performance index in patients with asphyxia was higher than that in patients without asphyxia. We concluded that patients with mild asphyxia have a mild cardiac dysfunction and this change can be detected by a myocardial performance index.

Aims: Breast feeding is particularly important and difficult in children born prematurely, especially after hypertensive diseases in pregnancies (HDP). Therefore, we aimed to investigate breast feeding in women who developed HDP. Methods: Data on breast-feeding was collected within a nationwide research project on psychosocial factors in HDP. A self-administered questionnaire was given to 2600 women with a suspected history of HDP and 1233 controls. After matching and confirming diagnosis according to ISSHP criteria, 877 women with HDP and 623 controls were included into the study. Results: Control women initiated (48.9/39.2%; P<0.001) and continued (42.2/37.2%; P<0.005) breast-feeding significantly more often than women with HDP. This holds particularly for women who developed HELLP syndrome (48.9/34.7%; P<0.0001, 42.2/33.5%; P<0.0001). A delivery before the 32 nd gestational week (19.5/81.8%; P<0.0001) and a birth weight of less than 1500 g (18.8/75%; P<0.0001) were associated with the decision not to breast-feed. Conclusions: Women affected by HDP breast fed significantly less often than control women. This effect is at least partly caused by the increased rate of prematurity. Encouraging and supporting these women in breast-feeding is important to improve neonatal physical and mental development.

Parvovirus B19-infected hydrops fetalis was treated using gammaglobulin injection into the peritoneal cavity (GIFPeC) with B19-IgG-rich immunoglobulin. Fetal anemia and hydrops resolved, and B19-DNA in fetal ascites decreased despite no change in maternal B19-IgG or B19-DNA. Gammaglobulin injection into the peritoneal cavity is thus useful for treating hydrops fetalis while avoiding intrauterine blood-transfusion risks.

We present a patient with a placenta previa in which we failed to manage conservatively with methotrexate and uterine embolization. The patient was diagnosed in the second trimester as having a possible placenta previa-increta, and underwent a repeat classical cesarean delivery at 32 weeks of gestation due to significant antepartum vaginal bleeding. Following abdominal closure, the uterine vessels were embolized with the Gel-Foam by interventional radiology. The placenta previa was left in-situ and patient was discharged home in stable condition in five days. The patient reported on the 44 th postoperative day with heavy vaginal bleeding. A total abdominal hysterectomy was performed due to an unstable patient's hemodynamic condition in association with fluid resuscitation and multiple blood transfusions. The pathologic findings revealed a 675 g uterus with placenta previa-percreta with extension of chorionic villi to the serosal layer. Our case demonstrates a need for careful selection of patients with placenta previa and suspected accreta/increta/percreta that would be suitable candidates for conservative medical management. Patients who opt for conservative medical management should be informed about the possibility of catastrophic bleeding associated with a retained placenta, that would ultimately require blood transfusions and hysterectomy.