Placental pathology in fetal growth restriction

Objectives

One of the causes of intrauterine fetal growth restriction (FGR) can be pathology of the placenta. The aim of this study was to compare macroscopic and microscopic changes of the placentas from intrauterine growth restricted fetuses with those from normally developed fetuses, in order to test the hypothesis that vascular damage due to decreased maternal vascular perfusion may be responsible for FGR.

Study design

Between May 2007 and December 2008 we performed detailed macroscopic and histological examination of singleton placentas of 50 consecutive neonates with fetal growth restriction (FGR group) and compared them to 50 normal fetuses, born next to an FGR case, as a control group.

Results

Gestational age, birth weight, spontaneous delivery rate, mean weight of the placenta and the fetal-placental weight ratio were all lower in the FGR group than in the control group (p < 0.05). Thickening of the villous trophoblastic basal membrane, incidence of villous infarction, presence of thrombi or haematomas and the incidence of villitis were more common in the FGR group than in the controls (p < 0.05). There were, however, no significant differences in perivillous fibrin deposition, stromal fibrosis and cytotrophoblast proliferation between the groups. In FGR women who smoked, intervillous haematomas and villous infarction were more common (p < 0.05) than in controls.

Conclusions

All macroscopic and microscopic pathological changes associated with FGR were directly linked to reduction of placental blood flow. As smoking is a main risk factor for these placental abnormalities these results emphasize the need to persuade women to quit smoking not only during pregnancy, but even better long before pregnancy.     

Prenatal diagnosis of chromosomal abnormalities in a resource-poor setting

Objective

To compare the efficacy and efficiency of systematic, ultrasound-based risk adjustment using a published algorithm with that of a maternal age cutoff of 37 years for the prenatal detection of chromosomal abnormalities (especially autosomal trisomies).

Methods

These approaches were compared in a retrospective study of 136 chromosomal abnormalities confirmed by karyotyping prenatally (n = 46) or postnatally (n = 90). There were 114 autosomal trisomies.

Results

Maternal age was known for 103 fetuses with confirmed abnormalities. The ultrasound-based risk adjustment approach was more sensitive for autosomal trisomy (93.9% vs 44.1%), and karyotyping for younger women with abnormalities on ultrasound was more effective than routine karyotyping in older women (1 trisomy detected in 13.5 vs 42.8 samples, P < 0.001). A lack of screening was the main reason for the postnatal diagnosis.

Conclusion

Ultrasound-based risk adjustment was the more effective approach.     

Combined use of the cardiofemoral index and middle cerebral artery Doppler velocimetry for the prediction of fetal anemia

Objective

To assess the accuracy of the combined use of the cardiofemoral index (CFI) and the middle cerebral artery peak systolic velocity (MCA-PSV), converted to multiples of the median (MoM), as noninvasive means to detect severe fetal anemia.

Method

We measured CFI and MCA-PSV MoM in 37 fetuses just before their first (n = 37), second (n = 22), and third (n = 14) cordocenteses and transfusions. Then, using 2 different criteria for severe fetal anemia detection (Hb deficit ≥ 7 g/dL and hemoglobin level ≤ 0.55 of MoM), we assessed their hemoglobin status during cordocentesis and the accuracy of CFI and MCA-PVS was determined.

Results

At the first cordocentesis the mean hemoglobin level was 8.5 ± 3.6 g/dL and 15 fetuses (40.5%) had hydrops. In a total of 81 fetal evaluations, 58 (71.6%) of the CFIs and 34 (42.0%) of the MCA-PSV MoM measurements were abnormal. The result of one of these tests was abnormal in 65 evaluations (80.3%) and the results of both tests were abnormal in 27 evaluations (33.3%). All fetuses diagnosed as being severely anemic by at least one of the hemoglobin criteria during cordocentesis had an abnormal result by at least one of the noninvasive tests. Before the second and third transfusions, the combined use of the CFI and MCA-PSV MoM predicted severe fetal anemia with 100% sensitivity. When the CFI and MCA-PSV MoM measurements were normal, the negative likelihood ratio was zero.

Conclusion

When associated, CFI and MCA-PSV MoM were accurate predictors of severe fetal anemia.     

Association between gestational age and induction-to-abortion interval in mid-trimester pregnancy termination using misoprostol

Objective

The study was aimed to evaluate the effectiveness, outcome, and pain intensity of the vaginal administration of misoprostol for the induction of abortion between 13 and 24 gestational weeks.

Study design

A retrospective study was conducted at our tertiary medical center from January 2006 to December 2009 on 122 consecutive women who underwent termination of pregnancy (TOP) in the mid-trimester. They were given 400 mcg of vaginal misoprostol every 6 h, up to four doses. The induction-to-abortion interval and the level of pain experienced during the process were assessed. Success was defined by the fetus being expelled within 48 h.

Results

Vaginal misoprostol was effective in 84% (98/122) of patients. The median duration of the induction-to-abortion interval was 16 (5-48) h. The induction-to-abortion interval was correlated with gestational age, while inversely correlated with parity. A correlation was also found between gestational age and pain intensity at 12 h from induction.

Conclusion

Misoprostol is safe and effective in mid-trimester abortion induction. The induction-to-abortion interval is shorter and abortion less painful with lower gestational age. Higher parity is also associated with shorter induction to abortion interval.     

Use of fetal colon thickness for auxiliary term dating of pregnancy

Objective

To verify whether fetal colon thickness can be used as a marker for estimating, independent of biometrics and fetal weight percentile, the gestational age (GA) of fetuses between 37 and 40 weeks.

Methods

The study group was 1296 fetuses aged between 33 and 40 weeks. The correlation between GA and colon thickness was assessed by the Pearson correlation test. For term fetuses (≥ 37 weeks), comparisons among the mean colon thickness for different weight percentiles at each GA (in weeks) were made with an analysis of variance test.

Results

A significant relationship was observed between GA and colon thickness (P < 0.001, r² = 0.6). For term fetuses, significant differences were observed among the mean colon thickness values for different weight percentiles at 38 and 39 weeks. Of the 157 term fetuses for which biometrics would have underestimated GA by 2 weeks or more, 126 (80.3%) had a colon thickness equal to, or greater than, 14 mm. This colon thickness was also observed in 52 (70.3%) of term fetuses weighing less than the 10th percentile (n = 74).

Conclusion

The present study suggested that colon thickness might be a good marker for 37 weeks of gestation, and might identify term fetuses for which biometrics has underestimated the GA.     

Fetal facial sonographic markers for second trimester Down syndrome screening in a Thai population

Objective

To assess the efficacy of using facial sonographic markers for screening fetuses in the second trimester for Down syndrome (DS) in a high-risk Thai population.

Method

Frontomaxillary facial angle (FMF) and nasal bone length (NBL) were measured prospectively in pregnant women at high-risk for DS who were undergoing genetic amniocentesis from November 2008 to October 2009. The receiver operator characteristic (ROC) curves were constructed to assess the screening efficacy of FMF angle and NBL.

Result

A total of 460 pregnant women were recruited, and a mid-sagittal facial profile was obtained for 403 fetuses. There were 386 fetuses with normal chromosomes, 10 fetuses with DS, 1 fetus with trisomy 13, and 1 fetus with trisomy 18. The remaining 5 fetuses had balanced translocation (n = 2), deletion (n = 1), and mosaic Turner (n = 2). Two different combinations of FMF angle and biparietal diameter to nasal bone length (BPD:NBL) ratio for DS screening in the second trimester achieved 50% and 90% detection rates and 4.4% and 14.0% false positive rates, respectively.

Conclusion

The combination of FMF angle and BPD:NBL ratio has a high sensitivity and specificity for screening for DS in the second trimester in a high-risk Thai population.     

A Phase I Study using low-dose fractionated whole abdominal radiotherapy as a chemopotentiator to full-dose cisplatin for optimally debulked stage III/IV carcinoma of the endometrium

Objective

To evaluate the feasibility of combining low-dose fractionated whole abdominal radiation (LDF-WAR) with weekly full-dose cisplatin (FD-CDDP) for patients with stage III/IV endometrial carcinoma.

Methods

Patients with optimally debulked stage III/IV carcinoma of the endometrium (without extra-abdominal disease) were eligible for the study. Postoperatively, patients received the institutional standard systemic chemotherapy and vaginal brachytherapy. Patients then underwent experimental six weekly cycles of FD-CDDP (40 mg/m², maximum 70 mg IV) followed by LDF-WAR 6-8 hours after initiation of chemotherapy. In a conservative design, 6 patients were accrued to two sequential cohorts of LDF-WAR, at 0.5 Gy/fraction [Fx] (total 3 Gy) and 0.75 Gy/Fx (total 4.5 Gy). Toxicities and laboratory studies were evaluated at each visit.

Results

Twelve patients were enrolled from January 2005 to June 2009 with median follow-up of 13.5 months (range: 5-27 months). Seventy-five percent of enrolled patients had uterine papillary serous histology. Eleven patients at least partially completed therapy (range: 2-6 cycles of FD-CDDP/LDF-WAR) with one additional patient opting out at the higher dose level. Combination therapy overall was well tolerated. Three patients in each cohort experienced grade 3 acute hematologic events with one recorded grade 4 toxicity in the second cohort. Of patients receiving any of the experimental treatment, five have experienced recurrences. Three of these patients were in cohort one and received 0.5 Gy/Fx LDF-WAR.

Conclusion

Combination therapy with LDF-WAR as a novel chemopotentiator to FD-CDDP is a feasible adjuvant regimen in optimally debulked patients with stage III/IV endometrial carcinoma. Further investigation is warranted to determine treatment efficacy.     

Secreted cyclophilin A induction during embryo implantation in a model of human trophoblast-endometrial epithelium interaction

Objective

The aim of this study was to show glycemic and oxidative/antioxidative status (GOAS) in rats with estradiol valerate (EV)-induced polycystic ovarian syndrome.

Study design

Thirty mature female rats were randomly allocated to EV-induced PCOS, sham and control groups. Malondialdehyde, catalase and fasting blood glucose levels were determined in order to evaluate GOAS.

Results

There was a statistically significant difference between PCOS and control groups (p < 0.001) for hemolysate MDA while no difference was determined for either catalase or fasting blood glucose levels. On histopathological examination, the EV-induced PCOS group revealed disease-characteristic ovarian morphology.

Conclusion

There was an increased compensation for oxidative stress by antioxidative biologic mechanisms in EV-induced PCOS rats. Interestingly, the sole result derived from this limited study is that the sesame oil + EV combination is not appropriate for the evaluation of oxidant-antioxidant status and also glycemic condition in PCOS. This study demonstrates the need for better designed experimental studies to elucidate the aetiopathogenesis of PCOS via novel techniques.     

Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study

Objective

To investigate the efficacy and safety of oral dienogest 2 mg compared with placebo in the treatment of endometriosis-associated pelvic pain (EAPP).

Study design

This was a 12-week, randomized, double-blind, placebo-controlled, multicenter (n = 33) study in Germany, Italy, and Ukraine of 198 women aged 18-45 years with laparoscopically confirmed endometriosis and EAPP score ≥30 mm on a visual analog scale (VAS). Dienogest 2 mg or placebo was administered orally once daily. The primary efficacy variable was absolute change in EAPP from baseline to Week 12, as determined by the target variables of change in VAS score and change in intake of supportive analgesic medication (ibuprofen) for pelvic pain.

Results

Mean reductions in VAS score between baseline and Week 12 in the full analysis set were 27.4 mm and 15.1 mm in the dienogest and placebo groups, respectively—a significant score difference of 12.3 mm in favor of dienogest (P < 0.0001). Changes in intake of supportive analgesic medication were modest in both groups. The primary efficacy measure of absolute change in EAPP demonstrated the superiority of dienogest over placebo. Dienogest was generally well tolerated and few adverse events were associated with therapy.

Conclusions

Dienogest at a dose of 2 mg daily for 12 weeks was significantly more effective than placebo for reducing EAPP.     

Prenatal antibiotic treatment does not decrease group B streptococcus colonization at delivery

Objective:

To evaluate whether an outpatient antibiotic regimen decreased group B streptococcal (GBS) colonization to preclude the use of intrapartum antibiotics.

Methods:

A double-blind randomized controlled trial evaluating prenatal oral amoxicillin versus placebo with the primary outcome of GBS colonization at the time of labor.

Results:

Of those patients receiving both amoxicillin and a repeat culture at the time of labor, 6 of the 14 (43%) tested positive for GBS colonization. Given persistent GBS colonization of 67% (10/15) in the placebo group, treatment with amoxicillin did not significantly impact colonization at the time of delivery (P = 0.20).

Conclusion:

A regimen of outpatient amoxicillin was associated with persistent GBS colonization in 43% of women at the time of labor. Oral prenatal antibiotic prophylaxis against GBS does not sufficiently reduce colonization to preclude intrapartum intravenous antibiotics.     

Outcomes of patients with gynecologic malignancies undergoing video-assisted thoracoscopic surgery (VATS) and pleurodesis for malignant pleural effusion

Objectives

We evaluated the indications and outcomes of patients with known gynecologic malignancies that underwent video-assisted thoracoscopic surgery (VATS) and pleurodesis for malignant pleural effusion.

Methods

After IRB approval was obtained, a retrospective study of patients with gynecologic malignancies who underwent planned VATS/pleurodesis between 1/2000 and 7/2010 was performed. Abstracted data included demographics, diagnosis, disease status, treatment history, indication for VATS, complications, and outcomes.

Results

Forty-two patients with a gynecologic malignancy underwent VATS/pleurodesis. Median age was 63 years. Twenty-nine patients (69%) had ovarian cancer. Fifty-seven percent had recurrent disease at the time of VATS and 57% were undergoing chemotherapy at the time of VATS. Eight patients (19%) underwent perioperative VATS to improve pulmonary status. Seven patients (17%) underwent a palliative VATS. The median length of stay was 7 days (range 1-53). Sixty-two percent had gross disease noted at the time of VATS. A mean of 1650 cc of fluid was drained at time of surgery (range 300-4500), and the majority (88%) of patients had a talc pleurodesis performed. Seven patients (17%) were readmitted within 30 days; 6 were for complications unrelated to their VATS. One patient was readmitted with hospital-acquired pneumonia and died during readmission. Median time to death after VATS was 104 days (range 4-1062). Patients who underwent a perioperative VATS had the longest survival (845 days).

Conclusion

Patients with gynecologic malignancies may require a VATS/pleurodesis for symptomatic pleural effusions. This procedure appears to be safe and effective in this patient population.     

Midwifery in a new context: expanding our reference points and embracing new representations of pregnancy and birth

Objective

to learn the adaptations and transformations that midwives from abroad must go through in order to integrate into the practice of Quebec midwifery, which is founded on a concept of birth akin to the holistic model.

Design

qualitative research achieved through semi-structured interviews with an ethnological approach for data collection and analysis.

Setting

Quebec, Canada.

Participants

11 immigrant midwives practising in Quebec. Interviews were also conducted with midwives from Quebec trained abroad (3) and trained in Quebec (5).

Findings

the greatest challenge for most of the midwives interviewed has been the change of professional culture. Shifting from a technocratic or medical practice model towards a holistic practice model has expanded their points of reference. Medical knowledge has become a type of shared knowledge, with each contributor judged equally important. Nature and humanity now prevail over technology. The woman has become the primary reference source for decision-making. For some midwives of foreign origin, integration into the Quebec practice provided an opportunity to reflect upon or modify their perception of pregnancy. In terms of representations, although most of the midwives interviewed now consider childbirth a life-affirming experience; for others, it represents a potential risk of complications or catastrophes. This apprehensiveness is more significant among midwives who have been trained in a medical model and who come from a country where the medical culture is socially dominant.

Key conclusions

midwives from highly medicalized environments face a greater adjustment when integrating into Quebec's practice culture. They must shift from a ‘risk’ mindset to a ‘confidence’ mindset and develop their trust in the normal process of pregnancy and childbirth. They must acquire a sense of inner security on which they can rely instead of systematically resorting to technological referents. This adjustment of referents and representations is an operative transformation process that is often accompanied by changes in identity.

Implications for practice

to facilitate the integration of immigrant midwives, it is important to consider the professional culture changes they face. If they are to use a holistic practice model, they must engage in introspection. They must reflect on pregnancy and childbirth if they are to consider these events first and foremost as a healthy, integral part of women's lives.     

Chemoradiation and adjuvant chemotherapy in advanced cervical adenocarcinoma

Purpose

The optimal treatment of women with advanced adenocarcinoma of uterine cervix is still undefined. We compared concurrent chemoradiation (CCRT) and adjuvant cisplatin-based chemotherapy with CCRT alone for advanced cervical adenocarcinoma in a randomized trial at the Hunan Provincial Tumor Hospital in China.

Methods

From 1998 to 2007, 880 patients with clinical FIGO stages IIB-IVA cervical adenocarcinoma were randomized to receive either CCRT or chemoradiation with one cycle of neo-adjuvant chemotherapy with Paclitaxel (135 mg/m²) + Cisplatin (75 mg/m²) before receiving radiation and two cycles of consolidation chemotherapy with the same drugs after radiotherapy in 3-week intervals. The disease control and survival rates were calculated using the Kaplan-Meier method.

Results

All patients completed the treatment plan. 340 patients have relapsed, with a median follow-up duration of 60 months. Patients who received chemoradiation with adjuvant chemotherapy showed a significantly longer disease-free (P < .05), cumulative survival (P < .05) and long-term local tumor control (P < .05). Patients who received CCRT alone had significantly more distant metastasis and pelvic failure than those who received chemoradiation with adjuvant chemotherapy (P < .05).

Conclusion

Incorporating neo-adjuvant and consolidation chemotherapy with Paclitaxel and Cisplatin into concomitant chemoradiation is highly effective, safe and may be a very promising treatment protocol for advanced cervical adenocarcinoma.     

Minimal deviation adenocarcinoma of the uterine cervix

Background

Precise preoperative diagnosis of minimal deviation adenocarcinoma (MDA) of the uterine cervix is often difficult because the histological features of MDA closely resemble those of normal cervical glands.

Objective

To review the developments in the diagnosis and treatment of MDA over the past 35 years.

Search strategy

We performed a meta-analysis of all case reports published in the English and Chinese languages between 1975 and 2009 that included a histopathologic diagnosis of MDA. Pooled odds ratios and 95% CIs were calculated for comparisons and analyzed.

Results

The histopathologic diagnosis of MDA remains difficult and is currently based on antigen detection by immunohistochemistry. Cytologic assessment and routine biopsy have low detection rates for MDA. Cross-sectional imaging techniques are helpful but a deep cervical biopsy or cervical conization is necessary for a definitive diagnosis. The mean survival is about 5 years for patients with stage I, 38.1 months for patients with stage II, 22.8 months for patients with stage III, and 5.4 months for patients with stage IV MDA.

Conclusion

Early diagnosis and treatment are key to improving prognosis and survival in patients with MDA.     

Body Mass Index and spontaneous miscarriage

Objective

We compared the incidence of spontaneous miscarriage in women categorised as obese, based on a Body Mass Index (BMI) >29.9 kg/m², with women in other BMI categories.

Study design

In a prospective observational study conducted in a university teaching hospital, women were enrolled at their convenience in the first trimester after a sonogram confirmed an ongoing singleton pregnancy with fetal heart activity present. Maternal height and weight were measured digitally and BMI calculated. Maternal body composition was measured by advanced bioelectrical impedance analysis.

Results

In 1200 women, the overall miscarriage rate was 2.8% (n = 33). The mean gestational age at enrolment was 9.9 weeks. In the obese category (n = 217), the miscarriage rate was 2.3% compared with 3.3% in the overweight category (n = 329), and 2.3% in the normal BMI group (n = 621). There was no difference in the mean body composition parameters, particularly fat mass parameters, between those women who miscarried and those who did not.

Conclusions

In women with sonographic evidence of fetal heart activity in the first trimester, the rate of spontaneous miscarriage is low and is not increased in women with BMI > 29.9 kg/m² compared to women in the normal BMI category.     

The administration of metformin during pregnancy reduces polycystic ovary syndrome related gestational complications

Objectives

To prospectively evaluate the safety of metformin administration during pregnancy in a group of PCOS patients by assessing its effect on the prevalence of gestational complications and neonatal outcome.

Study design

Our prospective, single centre study included 98 pregnant women with PCOS treated with metformin throughout pregnancy and 110 normal pregnant controls. All PCOS patients were hyperinsulinemic and received metformin (1700-3000 mg/day) before conception and until 37 weeks’ gestation.

Results

Metformin treatment in the pregnant PCOS patients resulted in significant decrease in miscarriage rate (9.1% vs 20%; p < 0.05), gestational diabetes (0 vs 13%; p < 0.005), and gestational hypertension (0 vs 11%; p < 0.005) and a non-significant decrease in pre-eclampsia (0 vs 3%; p = .24), compared to the control group. Mean neonatal Apgar score, weight and length were comparable between the two groups.

Conclusions

Continuing metformin therapy throughout pregnancy resulted in significant reduction in pregnancy complications with concomitant improved neonatal outcome, with no serious deleterious side effects.     

Intravenous nitroglycerin for controlled cord traction in the management of retained placenta

Objective

To determine the effect of 200 μg of intravenous nitroglycerin in the release of retained placenta by controlled cord traction.

Methods

In this randomized controlled study, 40 women with a placenta retained for 30 minutes received intravenously 200 μg of nitroglycerin or a normal saline solution before umbilical cord traction was initiated. The rates of successful removal of the retained placenta in the study (n = 20) and control (n = 20) groups were compared, as were blood pressure, pulse rate, blood loss, and adverse effects.

Results

The placenta was released in only 15% and 20% of the participants in the study and control group, respectively. The remainder of the participants required general anesthesia and manual removal of the retained placenta regardless of group assignation. Blood pressure fell in significantly more women in the study group, but there were no differences in estimated blood loss or minor adverse effects.

Conclusion

Intravenously administered nitroglycerin did not facilitate the release of retained placenta by umbilical cord traction. However, cord traction may be performed longer than 30 minutes to attempt releasing the placenta before operative manual removal is initiated.     

Evaluation of Fanconi anaemia genes FANCA, FANCC and FANCL in cervical cancer susceptibility

Objective

Disrupting the function of any of the 13 Fanconi anaemia (FA) genes causes a DNA repair deficiency disorder, with patients being susceptible to a number of cancer types. Variation in the family of FA genes has been suggested to affect risk of cervical cancer. The current study evaluates the influence of three genes in the FA pathway on cervical cancer risk in Swedish women.

Methods

TagSNPs in FANCA, FANCC and FANCL were selected using the Tagger algorithm in Haploview. A total of 81 tagSNPs were genotyped in 782 cases (CIN3 or ICC) and 775 controls using the Illumina GoldenGate Assay and statistically analyzed for association with cervical cancer.

Results

72 SNPs were successfully genotyped in > 98% of the samples. Nominal associations were detected for FANCA rs11649196 (p = 0.05) and rs4128763 in FANCC (p = 0.02). The associations did not withstand correction for multiple testing.

Conclusions

The current study does not support that genetic variation in FANCA, FANCC or FANCL genes affects susceptibility to cervical cancer in the Swedish population.     

Implementation of the Zambia Electronic Perinatal Record System for comprehensive prenatal and delivery care

Objective

To characterize prenatal and delivery care in an urban African setting.

Methods

The Zambia Electronic Perinatal Record System (ZEPRS) was implemented to record demographic characteristics, past medical and obstetric history, prenatal care, and delivery and newborn care for pregnant women across 25 facilities in the Lusaka public health sector.

Results

From June 1, 2007, to January 31, 2010, 115 552 pregnant women had prenatal and delivery information recorded in ZEPRS. Median gestation age at first prenatal visit was 23 weeks (interquartile range [IQR] 19-26). Syphilis screening was documented in 95 663 (83%) pregnancies: 2449 (2.6%) women tested positive, of whom 1589 (64.9%) were treated appropriately. 111 108 (96%) women agreed to HIV testing, of whom 22% were diagnosed with HIV. Overall, 112 813 (98%) of recorded pregnancies resulted in a live birth, and 2739 (2%) in a stillbirth. The median gestational age was 38 weeks (IQR 35-40) at delivery; the median birth weight of newborns was 3000 g (IQR 2700-3300 g).

Conclusion

The results demonstrate the feasibility of using a comprehensive electronic medical record in an urban African setting, and highlight its important role in ongoing efforts to improve clinical care.