Perinatal mortality and advanced maternal age.

OBJECTIVE: To investigate the impact of advanced maternal age on the rate of perinatal mortality. DESIGN: Retrospective cohort study including all 56,517 singleton hospital deliveries between 1999 and 2008. METHODS: Data were analyzed according to maternal age at delivery in 3 groups of women, 25-34 years, 35-39 years and ≥ 40 years, using the youngest as the reference group. RESULTS: Odds ratios (ORs) for antenatal deaths were 0.98 (CI: 0.67-1.43) and 2.57 (CI: 1.57-4.22) for age groups 35-39 years and ≥ 40 years, respectively. Significant differences in neonatal mortality rates between the age groups were not found. Significant amendable risk factors were attendance of <4 health care visits (OR = 15.55, CI: 9.47-25.51 in age group 35-39 years; OR = 16.38, CI: 9.78-27.43 in the age group ≥ 40 years) and obesity (OR = 1.85, CI: 1.27-2.70 in age group 35-39 years; OR = 1.83, CI: 1.22-2.74 in the age group ≥ 40 years). In the multivariate regression analysis, the adjusted ORs for perinatal mortality were 1.03 (95% CI: 0.77-1.39) and 1.66 (95% CI: 1.03-2.66) for age groups 35-39 and ≥ 40, respectively. CONCLUSIONS: Women older than 40 years carry an increased risk for stillbirth. Important amendable risk factors are obesity and poor antenatal care.

Novel RHD alleles with weak hemagglutination and genetic Exon 9 diversity: weak D Types 45.1, 75, and 76.

BACKGROUND: Molecular variant RHD allele analysis is best complemented by detailed characterization of the associated D phenotype. STUDY DESIGN AND METHODS: Variant D types were characterized using molecular typing, RHD sequencing, extended serologic D antigen investigations, and flow cytometric D antigen quantification. RESULTS: We discovered three novel weak D types termed weak D Types 45.1, 75, and 76 with RHD nucleotide substitutions coding for amino acid exchanges in predicted intracellular RhD polypeptide stretches; antigen densities of approximately 1.990, 900, and 240 D sites per red blood cell were found, respectively. Adsorption-elution technique-supported D epitope mapping of these three weak D types demonstrated the expression of all tested D epitopes. Initial molecular typing of the three investigated samples by RHD gene exon scanning polymerase chain reaction using sequence-specific priming yielded a negative reaction for A1193 located in RHD Exon 9 and could be explained by specific mutations for weak D Types 45.1 (C818T, G1195A), 75 (G1194C), and 76 (A1215C). CONCLUSION: All novel weak D types expressed all tested D epitopes. It is of interest that for weak D Types 45.1, 75, and 76, similar alleles with a maximal divergence of one amino acid only, that is, weak D Types 45, 41, and 68, respectively, have been reported so far.

Conservative management of abnormally invasive placenta: four case reports.

Prenatal diagnosis of placenta increta and percreta is essential to avoid potentially life-threatening hemorrhage by optimizing peripartal management. Invasive placentation presents significant challenges at cesarean section even for highly skilled surgeons. In the four cases of placenta increta/percreta presented here we tried to avoid hysterectomy by leaving the placenta behind and tried to accelerate regression of placental tissue by administering methotrexate. The outcome in each of the four women was different, but no major bleeding occurred in any of the cases. Close follow-up for many weeks is mandatory.

Nitisinone treatment during two pregnancies and breastfeeding in a woman with tyrosinemia type 1 - a case report.

OBJECTIVES: Tyrosinaemia type 1, an inherited disorder of tyrosine metabolism, is usually treated with a tyrosine-defined diet and since 2000 with nitisinone. So far, data about effects of nitisone during pregnancy and breastfeeding are rare. This is the first report of two pregnancies in a patient with tyrosinaemia type 1 while under treatment with nitisinone. CASE PRESENTATION: We here present a 20-year-old female patient with tyrisonemia type 1 receiving treatment with nitisinone and a tyrosine-defined diet since she was diagnosed with tyrosinaemia type 1 at the age of 18 months. During two pregnancies blood concentrations of tyrosine, succinylacetone and nitisinone were measured regularly. Neither infant has tyrosinaemia type 1 and both showed an initial increase in concentrations of tyrosine, succinylacetone and nitisinone. All three metabolites dropped within two weeks after birth. Both were exclusively breastfed for about two weeks. Both children show age-appropriate physical and mental development. CONCLUSIONS: Nitisinone therapy during pregnancy and the short breastfeeding period did not result in adverse events in our patient or her children. Regular assessments of tyrosine, succinylacetone and nitisinone should be made during pregnancy and the breastfeeding period in both the mother and the infant. For better understanding, in principle, all cases of pregnancy and breastfeeding with tyrosinemia type 1 should be assessed and followed to further evaluate the implications of tyrosinaemia type 1 and its treatment during pregnancy. Additionally, even though experience with breastfeeding is limited, medication with nitisinone is safe and there is no reason to consider breastfeeding unsafe or to not recommend it.

Prevalence of iron deficiency in pregnant women: A prospective cross-sectional Austrian study.

The aim of the study was to determine, for the first time, in a prospective cross-sectional multicenter study, the prevalence of iron deficiency (ID) in an Austrian pregnant population. A cohort of 425 pregnant women was classified into four groups of different weeks of gestation. Group 1 was monitored longitudinally, while groups 2-4, iron status, were sampled only once. Evaluation of the prevalence of ID was performed by comparing the diagnostic criteria of the WHO to the cutoff proposed by Achebe MM and Gafter-Gvili A (Achebe) and the Austrian Nutrition Report (ANR). In comparison with the ANR, the prevalence of ID was lower in group 1 and higher in groups 2-4 (17.2% vs. 12.17%, 25.84%, 35.29%, and 41.76%, respectively) (p-values < .01 except group 1). According to WHO, the prevalence in group 1 was 12.17% at inclusion, 2 months later 31.7%, and further 2 months later 65.71%, respectively. According to Achebe, the number of cases doubled; for group 1, the number of cases rose from 13 to 42 (115 patients total); for groups 2-4, we observed an increase from 112 to 230 (340 patients total). This study reported a prevalence of around 12% at the beginning of pregnancy, which increased during pregnancy up to 65%. ID can have a massive impact on quality of life, justifying screening, as iron deficiency would be easy to diagnose and treat.

Congenital fibrosarcoma as cause for fetal anemia: prenatal diagnosis and in utero treatment.

OBJECTIVES: To discuss diagnosis and management of a case of a rare fetal tumor complicated by fetal anemia due to intratumoral hemorrhage. CASE REPORT: We report on a 29-week-old fetus with a tumor in the posterior left shoulder region. The morphologic aspect of the tumor, lack of fetal movements and an increased middle cerebral artery (MCA) peak systolic velocity (PSV) were indicative of fetal anemia caused by intratumoral bleeding. Following intravascular blood transfusion the pregnancy was safely prolonged for 15 days, during which lung maturity was induced. After delivery the neonate underwent surgical excision. Histological examination revealed an infantile congenital fibrosarcoma. CONCLUSION: Anemia must be ruled out in cases with fetal tumors. MCA PSV is useful in diagnosis and surveillance in these fetuses.

Influence of the sFlt-1/PlGF Ratio on Clinical Decision-Making in Women with Suspected Preeclampsia.

OBJECTIVE: To evaluate the influence of the soluble fms-like tyrosine kinase 1/placental growth factor ratio in physicians' decision making in pregnant women with signs and symptoms of preeclampsia in routine clinical practice. METHODS: A multicenter, prospective, open, non-interventional study enrolled pregnant women presenting with preeclampsia signs and symptoms in several European perinatal care centers. Before the soluble fms-like tyrosine kinase 1/placental growth factor ratio result was known, physicians documented intended clinical procedures using an iPad® application (data locked/time stamped). After the result was available, clinical decisions were confirmed or revised and documented. An independent adjudication committee evaluated the appropriateness of decisions based on maternal/fetal outcomes. Clinician decision making with regard to hospitalization was the primary outcome. RESULTS: In 16.9% of mothers (20/118) the hospitalization decision was changed after knowledge of the ratio. In 13 women (11.0%), the initial decision to hospitalize was changed to no hospitalization. In seven women (5.9%) the revised decision was hospitalization. All revised decisions were considered appropriate by the panel of adjudicators (McNemar test; p < 0.0001). CONCLUSIONS: The use of the soluble fms-like tyrosine kinase 1/placental growth factor test influenced clinical decision making towards appropriate hospitalization in a considerable proportion of women with suspected preeclampsia. This is the first study to demonstrate the impact of angiogenic biomarkers on decision making in a routine clinical practice.

Analysis of aberrant DNA methylation and human papillomavirus DNA in cervicovaginal specimens to detect invasive cervical cancer and its precursors.

PURPOSE: Cancer of the uterine cervix is an important cause of death in women worldwide. Pap smears as a tool for screening decreased the incidence and mortality of cervical cancer dramatically. This proof of principle study aimed to develop a potential tool for cervical screening using a test that can be applied by patients without visiting a physician and to increase the coverage rate, especially of the high-risk population with low socioeconomic status. EXPERIMENTAL DESIGN: Human papillomavirus (HPV) DNA testing and methylation analysis of DNA obtained from cervicovaginal specimens of 13, 31, and 11 patients with no dysplasia/low-grade squamous intraepithelial lesion (SIL), high-grade SIL, and invasive cervical cancer, respectively, collected on a tampon, was performed using PCR-based methods to detect invasive cervical cancer and study whether these changes are already present in the precursor lesions. RESULTS: High-risk HPV DNA was present in 68 and 82% of patients with high-grade SIL and invasive cervical cancer. DNA methylation of the 11 genes tested increased with severity of the cervical lesion. Unsupervised hierarchical cluster analysis using solely information on DNA methylation of the 11 genes was able to predict the presence of invasive cervical cancers: one of the two clusters formed contained 9 of 11 invasive cervical cancers, as well as two high-grade SILs. CONCLUSIONS: HPV DNA and DNA methylation analyzed in cervicovaginal specimens are able to predict invasive cervical cancers. To detect all high-grade SILs when applying this test, genes that become methylated earlier throughout cervical carcinogenesis have to be defined.

Methylated DNA collected by tampons--a new tool to detect endometrial cancer.

This proof of principle study aimed to define a new and simple strategy for detection of endometrial cancer using epigenetic markers. We investigated DNA isolated from vaginal secretion collected from tampon for aberrant methylation of five genes (CDH13, HSPA2, MLH1, RASSF1A, and SOCS2) using MethyLight in 15 patients with endometrial cancer and 109 patients without endometrial cancer. All endometrial cancer patients revealed three or more methylated genes, whereas 91% (99 of 109) of the patients without endometrial cancer had no or fewer than three genes methylated in their vaginal secretion. The methods developed in this study provide the basis for a prospective clinical trial to screen asymptomatic women who are at high risk for endometrial cancer.

Migrants and obstetrics in Austria--applying a new questionnaire shows differences in obstetric care and outcome.

BACKGROUND: Immigration plays a major role in obstetrics in Austria, and about 18 % of the Austrian population are immigrants. Therefore, we aimed to (1) test the feasibility of a proposed questionnaire for assessment of migrant status in epidemiological research and (2) assess some important associations between procedures and outcomes in obstetrics and migration in selected departments in Austria. METHODS: We adapted a standardized questionnaire to the main immigration groups in Austria. Information on country of origin, length of residence in Austria and German-language ability was collected from eight selected obstetrics departments. Of the 1,971 questionnaires, 1,873 questionnaires of singleton births were selected and included in the analysis. RESULTS: We analyzed a total of 1,873 parturients with singleton births, of which 35 % had migrant status, 12 % were from ex-Yugoslavia, 12 % were from Turkey, and 12 % were from other countries. The proportion of parturients having their first care visit after the 12th week of pregnancy was higher in migrant groups (19 %). Smoking was highest in the migrants from ex-Yugoslavia (21 %). Vaginal delivery was more frequent in migrants from ex-Yugoslavia (78 %) and Turkey (83 %) than in nonmigrants (71 %) and episiotomy was more frequently performed in migrants from other countries. All differences are statistically significant. CONCLUSIONS: Administration of a standardized questionnaire for assessment of migrant status in obstetric departments in Austria was shown to be feasible. We assessed differences in obstetric care and outcome and consequently recommend that action should be initiated in Austria toward harmonizing obstetric procedures among the migrant and the nonmigrant groups and toward minimizing risk factors.

Malignant mixed mesodermal tumor after tamoxifen therapy for breast cancer.

BACKGROUND: The risk of tamoxifen related endometrial neoplasm has been confirmed by multiple studies. Especially rare endometrial tumors seem to develop more frequently under tamoxifen therapy. A recent analysis showed a substantially higher risk for malignant mixed mesodermal tumor (MMMT; designated in the WHO classification of female genital tract neoplasms as carcinosarcoma) in association with tamoxifen intake. CASE: We are reporting a case of a 40-year-old multiparous premenopausal woman who received tamoxifen 20 mg daily for 2 years after the surgical treatment of breast cancer and subsequent adjuvant chemotherapy. Two years after initiation of tamoxifen treatment, the patient developed an MMMT of the uterus. More than 64 months after radical hysterectomy, salpingo-oophorectomy, and pelvic lymphadenectomy, she remains recurrence-free for MMMT. Unfortunately, she developed a local recurrence of her breast cancer in 2003. After surgical treatment, she is currently being treated with anastrozole. CONCLUSION: We are reporting a rare case of a premenopausal patient who developed a MMMT within short time of tamoxifen exposure for stage I breast cancer.

Prognostic significance of Ep-CAM AND Her-2/neu overexpression in invasive breast cancer.

To assess the frequency and prognostic impact of Ep-CAM and Her-2/neu overexpression in patients with breast cancer and to determine its relationship with other prognostic markers, 205 breast cancer patients with a median follow-up of 10.8 years were enrolled in this retrospective study. Overexpression of Ep-CAM and Her-2/neu in tumor tissue samples was assessed by immunohistochemistry. Tumors presenting a Her-2/neu 2+ staining were additionally analyzed by FISH to exclude false positive results. Ep-CAM and Her-2/neu overexpression was found in 35.6% and 19.5% of the tumor samples, respectively. Both Ep-CAM and Her-2/neu overexpression were predictive for poor disease-free (DFS) and disease-related overall survival (DROS). Concurrent Ep-CAM and Her-2/neu overexpression was present in 13.2% of tumor specimens and had an additive negative impact on DFS and DROS. This minority of patients had a median time to relapse of only 34 months, whereas the median time to relapse was not reached in the patient population without Her-2/neu and Ep-CAM overexpression. By multivariate analysis Ep-CAM overexpression proved to be an indicator of poor prognosis, independent of tumor size, histologic grade, hormone receptor expression and Her-2/neu overexpression. In conclusion, overexpression of Ep-CAM and Her-2/neu complement each other as predictors for poor prognosis in patients with invasive breast cancer. Determination of these tumor markers should help in assigning breast cancer patients to 1 of 3 distinct risk categories.