Rolf Richter

Supplementation with 200 mg/Day Docosahexaenoic Acid from Mid-Pregnancy through Lactation Improves the Docosahexaenoic Acid Status of Mothers with a Habitually Low Fish Intake and of Their Infants

Background/Aims: The supply of docosahexaenoic acid (DHA, 22:6ω–3), important for fetal/infant neurodevelopment, depends on the maternal fatty acid (FA) status, which may be marginal in central Europe. Therefore, we investigated the effect of a daily vitamin/mineral supplement with and without 200 mg DHA from mid-pregnancy through lactation on the DHA concentrations in maternal and infant red blood cell phospholipids (RBC%), and in breast milk FA (%). Methods: At 21 weeks’ gestation, 144 women were enrolled into a randomised, double-blind clinical trial receiving daily: (1) a basic vitamin-mineral supplement (Vit/Min group), (2) Vit/Min plus 4.5 g fructo-oligosaccharide (FOS group), or (3) Vit/Min plus 4.5 g FOS plus 200 mg fish oil-derived DHA (DHA-FOS group). FAs were determined by capillary gas-liquid chromatography. Results: While maternal RBC-DHA% at enrolment was not different, at 37 weeks gestation, and 3 months after delivery RBC-DHA% were significantly higher in the DHA-FOS group. The breast milk DHA% was twice as high in the DHA-FOS group (0.50%) than in the two others (0.25 %) (p < 0.001), and the ratio ARA/DHA in the DHA-FOS group was 1.0 ± 0.43, in the others 2.1 ± 0.43 (p < 0.001). The RBC-DHA% of the infants in the DHA-FOS group was also significantly higher, and correlated significantly with maternal RBC-DHA% before and 3 months after delivery. Conclusions: In central Europe, a dose of 200 mg/day DHA from mid-pregnancy through lactation seems appropriate to improve the DHA status of mothers and infants.

Role of secondary cytoreductive surgery in ovarian cancer relapse: who will benefit? A systematic analysis of 240 consecutive patients.

In contrast to primary ovarian cancer, the value of surgery in relapsed‐OC (ROC) remains unclear. We evaluated surgical and clinical outcome of secondary cytoreduction in ROC.

Prevalence and risk factors for early postpartum anemia

OBJECTIVE To assess the prevalence and evaluate the most important risk factors for early postpartum anemia. STUDY DESIGN The perinatal process data of 43,807 women delivering between 1993 and 2008 (90.1% of all deliveries) in the largest university obstetric department in Germany were analyzed, and the associations of Hb<8 g/dl with maternal characteristics, pregnancy risks, delivery mode and estimated delivery blood loss were calculated. Multivariable logistic regression models were applied to compute odds ratios. Additionally, the impact of these risk factors for delivery blood loss was estimated with multivariable linear regression analysis. RESULTS Twenty-two percent of mothers had Hb<10 g/dl, and 3% had Hb<8 g/dl. The adjusted odds ratios (OR) for Hb<8 g/dl were 4.8 (p=0.001) for placenta previa, 2.9 (p<0.001) for mothers of African origin, 2.7 (p<0.001) for diagnosed anemia in pregnancy, 2.2 (p<0.001) for multiple pregnancy, and 2.1 (p=0.021) for bleeding in late pregnancy. However, the delivery blood loss was the most important risk factor for postpartum anemia. The adjusted OR for an estimated blood loss of 500-1000 ml was 15.3 (p<0.001), and for a loss of >1000 ml was 74.7 (p<0.001). CONCLUSION The estimated obstetric blood loss is the most important risk factor for severe postpartum anemia, and the volume of blood lost is especially high in cesarean deliveries, which should be considered when electing delivery procedures. Also, measures to boost iron stores in pregnancy should be established.

Does docosahexaenoic acid (DHA) status in pregnancy have any impact on postnatal growth? Six-year follow-up of a prospective randomized double-blind monocenter study on low-dose DHA supplements.

Abstract Fetuses and breastfed children depend on the maternal docosahexaenoic acid (DHA) supply, which might have long-lasting consequences. We studied the growth of 6-year-old children whose mothers received supplemental DHA from midpregnancy to 3 months after delivery. One hundred and forty-four pregnant women had been randomized to receive one of three vitamin-mineral supplements, one supplying an additional 200 mg/day DHA. Of the original sample, 120 children were measured at age 6 years with standardized methods. As one objective of the follow-up was to investigate the DHA influence on normal growth, the DHA group was compared with the pooled controls after exclusion of five premature infants. The weight, length, body mass index (BMI), head circumference, and skin-fold thickness at 6 years were similar in the 41 children of the DHA group and the 74 controls. Longitudinally, the BMI z-scores of the DHA group increased up at a later age than that of the controls. We found a highly significant negative correlation between height at 6 years and the increase in red blood cell DHA concentration of mothers from 22 to 37 weeks of pregnancy. We conclude that DHA supplements during midpregnancy corrected a low maternal DHA status (which correlated with children’s height) and was favorable in regard to the BMI development up to 6 years.

Preoperative HE4 and ROMA values do not improve the CA125 diagnostic value for borderline tumors of the ovary (BOT) - a study of the TOC Consortium

BackgroundBorderline tumors of the ovary (BOT) are a distinct entity of ovarian tumors, characterized by lack of stromal invasion. Recent studies postulated that the presence of invasive implants, incomplete staging, fertility sparing surgery and residual tumor after surgery are major prognostic factors for BOT. There are no biomarkers that can predict BOT or the presence of invasive implants.ObjectiveThe aim of our study was to assess the value of CA125 and HE4 alone, or within ROMA score for detecting BOT, and for predicting the presence of invasive implants.MethodsRetrospective, monocentric study on 167 women diagnosed with BOT or benign ovarian masses. Serum HE4, CA125 levels and ROMA were assessed preoperatively. Due to low number of BOT with invasive implants, we performed an unmatched analysis (consecutive patients) and a matched analysis (according to age and histology) to compare BOT with invasive implants, BOT without invasive implants and benign disease.ResultsThere were no significant differences in the HE4 and CA125 expressions in the three groups of patients (p = 0.984 and p = 0.141, respectively). The ROC analysis showed that CA125 alone is superior to ROMA and HE4 in discriminating patients with BOT with invasive implants from patients with benign diseases and BOT without invasive implants. A newly established score, ROMABOT, did not perform better than ROMA. The analysis of the matched groups revealed similar results as the analysis of all samples.ConclusionsBoth HE4 and CA125 are not reliable biomarkers for the diagnosis of BOT or for predicting the presence of invasive implants.

Role of serum concentration of VEGFR1 and TIMP2 on clinical outcome in primary cervical cancer: Results of a companion protocol of the randomized, NOGGO–AGO phase III adjuvant trial of simultaneous cisplatin-based radiochemotherapy vs. carboplatin and paclitaxel containing sequential radiotherapy

OBJECTIVE Aim of the present study was to analyze the expression-profile of IGF1, IGFBP3, sICAM1, sVCAM1, MMP2, MMP9, TIMP2, VEGFA, VEGFD, VEGFC and VEGFR1 in patients with high-risk FIGO-stage Ib-IIb cervical cancer. METHODS Serum from 68 cervical cancer patients treated within a phase-III-trial with either simultaneous cisplatin radiochemotherapy or sequential systemic carboplatin and paclitaxel followed by percutaneous irradiation was analyzed by ELISA. Both target expression and correlation with important clinicopathological factors were analyzed following standard statistic procedures. RESULTS All 68 patients underwent a primary radical hysterectomy with pelvic and/or paraaortic lymphadenectomy. 85.3% of the extirpated tumors had clear surgical margins (R0). Increased levels of VEGFR1, TIMP2 and MMP2 were significantly associated with positive surgical margins (p=0.004, p=0.018 and p=0.004, respectively). High concentration of MMP2 and TIMP2 correlated additionally with an advanced age at time of diagnosis (p=0.001 and p=0.007, respectively). For the cut-off value of 100 pg/ml, an increased VEGFR1 was significantly associated with poor overall (OS) and progression-free (PFS) survival (p=0.017 and p=0.015, respectively). A TIMP2 concentration of lower than 90 ng/ml was significantly associated with poorer OS and PFS (p=0.009 and p=0.043, respectively). In the multivariate analysis, TIMP2 expression in serum was the only independent prognostic factor for OS (p=0.032, HR=6.51, 95% CI=1.17-36.01). CONCLUSIONS Expression-profile of specific biomarkers associated with tumor invasion, cell migration and angiogenesis seems to be of prognostic value for both OS and PFS in patients undergoing surgery due to primary cervical cancer. Further analyses are warranted to allow an implementation of such markers into clinical practice.

The influence of polypharmacy on grade III/IV toxicity, prior discontinuation of chemotherapy and overall survival in ovarian cancer.

BACKGROUND Ovarian cancer is mostly diagnosed in the elderly woman who is likely to have comorbid disease and to take several comedications on a regular basis. Aim of this study was to evaluate the influence of polypharmacy on grade III/IV toxicity, prior discontinuation of chemotherapy and survival. PATIENTS AND METHODS In this individual participant data meta-analysis the original data of three phase II/III studies of the North-Eastern German Society of Gynecological Oncology (NOGGO) were analyzed using multivariate logistic and Cox regression. RESULTS Overall, 1213 patients with recurrent ovarian cancer were included in these analyses. An increasing amount of medication was associated with overall grade III/IV toxicity (p<0.001; OR 1.120), and hematological (p<0.001; OR 1.056) and non-hematological (p<0.001; OR 1.134) toxicities. Prior discontinuation of chemotherapy was not influenced by an increasing amount of medication (p=0.196). There was no association of polypharmacy with overall survival (p=0.068). CONCLUSION As polypharmacy does not influence survival ovarian cancer patients taking several comedications may be included in clinical trials and should not be deprived of adequate cancer treatment. However, a thorough monitoring is mandatory due to the increased risk of toxicities.

The influence of comorbidity and comedication on grade III/IV toxicity and prior discontinuation of chemotherapy in recurrent ovarian cancer patients: An individual participant data meta-analysis of the North-Eastern German Society of Gynecological Oncology (NOGGO)

BACKGROUND Ovarian cancer is usually a cancer of the older age group. Comorbidities and comedications increase with rising age. Aim of this study was to evaluate association of comorbidity and comedication with grade III/IV toxicities and prior cessation of chemotherapy in ovarian cancer patients. PATIENTS AND METHODS As an individual participant data meta-analysis this study analyzes the original data of three phase II/III chemotherapy studies of the North-Eastern German Society of Gynecological Oncology (NOGGO). Risk scores for certain combinations of risk factors were calculated based on stepwise regression analyses. RESULTS Altogether, 1213 patients were included in the study. Cardiovascular disease was the most frequent comorbidity (47.5%). In multivariate analyses it was associated with hematological, non-hematological, pulmonary and renal grade III/IV toxicities (p=0.002; p<0.001; p=0.005; p<0.001). Renal toxicity was more frequent when using diuretics and ACE-inhibitors (p<0.001; p=0.002). Prior cessation of therapy was e.g. associated with use of diuretics, insulin and digitalis (p=0.001; p=0.04; p=0.03). The risk for renal grade III/IV toxicities was more than 16 times higher when using both a diuretic and an ACE-inhibitor. CONCLUSIONS Regimens of ovarian cancer treatment should not be restricted to direct cancer therapy but rather include additional individualized treatment of comorbidities. Comedications such as diuretics increase grade III/IV toxicities and patients at risk should be closely monitored.

The prevalence of preterm deliveries in Berlin has not changed over 7 years: the impact of multiple births.

Abstract The problem of preterm deliveries has worsened in developed countries over the past decade. To evaluate whether multiple deliveries had an impact on this development, we analyzed the data of the Berlin Perinatal Survey from 1993–1999 for 206,308 deliveries. The prevalence of preterm deliveries was fairly constant during this period, and the proportion of preterm deliveries in the case of multiples remained constant. But the prevalence of preterm neonates increased significantly in Berlin due to an increased prevalence of multiple births. There was a significant increase of mothers aged over 30, of German nationality, and with preceding infertility treatment, while the prevalence rates of nearly all other risk factors for prematurity decreased over time. The risk of infertility treatments resulting in multiple deliveries increased in these years. On average, infertility treatment led to an about 10 times higher risk of producing multiples than singletons OR (95% Cl) of 9.6 (8.6–10.6).

Growth attainment in German children born preterm, and cardiovascular risk factors in adolescence. Analysis of the population representative KiGGS data

Abstract 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.