No further improvement in pregnancy-related outcomes in the offspring of mothers with pre-gestational diabetes in Bavaria, Germany, between 2001 and 2016.

AIMS: To investigate whether there has been further improvement in the risk of adverse outcomes in pregnancies in women with diabetes during 2008-2016 in Bavaria, Germany. METHODS: Using cross-sectional data on all 1716 170 deliveries in Bavarian hospitals between 2001 and 2016, we assessed the risks of stillbirth, early neonatal death, preterm delivery, large for gestational age, malformations, low Apgar score and low umbilical cord pH by maternal group with diabetes (gestational, pre-gestational, or none) separately for 2001-2007 and 2008-2016. We also investigated the associations of specific risk factors such as maternal smoking with respect to early mortality and malformations in each group with diabetes during 2008-2016. RESULTS: No further reduction in the risk for any adverse outcome in mothers with pre-gestational diabetes and their offspring during 2008-2016 was observed. Maternal smoking, multiple delivery and substandard antenatal care were the strongest additional predictors of both early perinatal mortality and malformations for mothers with pre-gestational diabetes. The respective risks were lower and also decreased over time for mothers with gestational diabetes. CONCLUSIONS: No significant improvement has been achieved in the management of pregnancies affected by pre-gestational diabetes during the last decade. The apparent risk reductions in women with gestational diabetes may partly be due to a change in diagnostic criteria over time. Women with pre-gestational diabetes who smoke, carry more than one child, or are not regularly seen during pregnancy, may need particular attention.

[Performance Indicators of Hospitals in One Region Between 2006/07 and 2013: a Trend Analysis]. / Trendanalyse der Qualitätsindikatoren der Krankenhäuser einer Region von 2006/07 bis 2013.

BACKGROUND: In spite of a nationwide implementation of performance indicators (PI) for monitoring inpatient medical care, a systematic evaluation of their development over time is still missing. METHODS: A trend analysis of annual rates of PI from 2006/07 to 2013 of Bavarian hospitals was conducted; 123 out of a total of 245 PI selected from 15 distinct clinical fields were available and comparable over the entire period and evaluated. Joinpoint regression was used to estimate annual percentage changes (APC) in regional averages. Individual hospital rates were inspected with box plots for selected indicators. RESULTS: 99 PI (80.5%) showed improvement over time, 67 (54.5% of all PI) were statistically significant. A change from positive to negative trend was found in 15 indicators (12.2%); the negative trend was significant only once. A continuous negative trend was observed in 9 cases (7.3%) (3 significant). Extreme values of hospital rates were present throughout the entire period of observation with results generally far below the national average. CONCLUSION: The majority of indicators improved continuously, which may be interpreted as indicating effectiveness of quality assurance programs, and could also give a strong impetus to further quality improvement measures.

Risk Stratification in Women with Gestational Diabetes According to and Beyond Current WHO Criteria.

The pregnancy outcomes in women with gestational diabetes mellitus (GDM) and 'overt diabetes in pregnancy' were compared and the need for further subclassification was investigated with respect to postpartum outcome risk. Data from 944 women who had been uniformly diagnosed as having GDM in Munich, Germany, between 1998 and 2010, were re-classified into GDM and 'overt diabetes in pregnancy'. Pregnancy related outcomes in the offspring were derived from Bavarian birth registry data. Classification and regression trees were used to identify further GDM sub-phenotypes. In total, 88 women (9.3%) were re-classified as having 'overt diabetes in pregnancy'. Compared to women with GDM, women with 'overt diabetes in pregnancy' used insulin more frequently, and were at increased risk for large for gestational age infants [odds ratio 2.50 (95% confidence interval 1.02, 6.13)], preterm delivery [odds ratio 3.28 (1.02, 10.50)], and low APGAR-score at 5 min [odds ratio 12.70 (1.58, 102.2)]. In the 856 women with GDM, classification and regression tree analyses provided further risk stratification in that a combination of fasting glucose>5.3 mmol/l and 1-h glucose>11.1 mmol/l at GDM diagnosis predicted insulin requirement [OR 5.57 (3.75, 8.27) compared to the rest], and maternal body mass index (BMI)≥35 kg/m(2) predicted large for gestational age status. The new differentiation between GDM and 'overt diabetes in pregnancy' is a first step towards refining classification relevant to fetal and maternal postpartum risk. A combination of glucose levels and maternal BMI at diagnosis of GDM may provide further improvement.

A global reference for caesarean section rates (C-Model): a multicountry cross-sectional study.

OBJECTIVE: To generate a global reference for caesarean section (CS) rates at health facilities. DESIGN: Cross-sectional study. SETTING: Health facilities from 43 countries. POPULATION/SAMPLE: Thirty eight thousand three hundred and twenty-four women giving birth from 22 countries for model building and 10,045,875 women giving birth from 43 countries for model testing. METHODS: We hypothesised that mathematical models could determine the relationship between clinical-obstetric characteristics and CS. These models generated probabilities of CS that could be compared with the observed CS rates. We devised a three-step approach to generate the global benchmark of CS rates at health facilities: creation of a multi-country reference population, building mathematical models, and testing these models. MAIN OUTCOME MEASURES: Area under the ROC curves, diagnostic odds ratio, expected CS rate, observed CS rate. RESULTS: According to the different versions of the model, areas under the ROC curves suggested a good discriminatory capacity of C-Model, with summary estimates ranging from 0.832 to 0.844. The C-Model was able to generate expected CS rates adjusted for the case-mix of the obstetric population. We have also prepared an e-calculator to facilitate use of C-Model (www.who.int/reproductivehealth/publications/maternal_perinatal_health/c-model/en/). CONCLUSIONS: This article describes the development of a global reference for CS rates. Based on maternal characteristics, this tool was able to generate an individualised expected CS rate for health facilities or groups of health facilities. With C-Model, obstetric teams, health system managers, health facilities, health insurance companies, and governments can produce a customised reference CS rate for assessing use (and overuse) of CS. TWEETABLE ABSTRACT: The C-Model provides a customized benchmark for caesarean section rates in health facilities and systems.

[Identification of city areas with an urgent need for early help in Munich: presentation of a new procedure on the basis of data on regional social structures and on the health risks of newborn babies]. / Ermittlung von Stadtgebieten mit hohem Bedarf an Frühen Hilfen in München: Vorstellung eines neuen Verfahrens auf Basis von Daten zur regionalen Sozialstruktur und zum gesundheitlichen Risiko von Neugeborenen.

BACKGROUND: In Germany, it is forbidden by law to physically punish children or to harm them mentally. Breaking these rules can result in severe health problems for the children. Home visiting programmes for families with young children are aimed at supporting young families who are facing large social problems, and at enhancing the chances of their children to grow up in a healthy way. Maps showing the regional distribution of the need for these home visiting programmes could be an important tool for local health policy planning. They could help to focus the resources on those families who are in greatest need. METHODS: The method proposed here for developing such a regional map is based on the following steps: (a) search for data that indicate the potential for child neglect, maltreatment or abuse, and that are available for each zip code in the city of Munich, Germany; (b) based on these data, calculation of a summary score that could indicate high need for these home visits; (c) grouping of the zip code areas according to this score; (d) presentation of the regional distribution in a map. RESULTS: After inspecting different data sources, we could identify 5 variables that could indicate the need for these home visits and that are available for each zip code: index of purchasing power, percentage of the population with low education, percentage of the population with migration background, percentage of single mothers, percentage of new-borns with low birth weight (<2 500 g). If 'high need' is defined as 'upper quintile of at least 3 among the 5 variables listed above, about 1 087 newborn babies would have to be visited per year (i. e., 10% of all newborn infants in Munich). CONCLUSION: These home visits should be as little stigmatising as possible, and especially those families should be reached that are in greatest need. If it is not possible to reach all families in the community, it can be recommended to focus on city districts with a high percentage of families in greatest need. As far as we know, this is the first scientifically based method for such a definition of city districts. The method proposed here could serve as starting point, and it would be important to develop it further. It is very flexible, though, and it can easily be transferred to other cities or districts.

Associations of gestational weight loss with birth-related outcome: a retrospective cohort study.

OBJECTIVE: Although the prevention of gestational weight loss (GWL) has become a priority for clinicians in the past few decades, recent work has suggested that GWL may be beneficial for obese mothers. We aimed to identify the potential beneficial or adverse associations of GWL with pregnancy outcome stratified by maternal body mass index (BMI) category. DESIGN: Retrospective cohort study. SETTING AND POPULATION: Data on 709 575 singleton deliveries in Bavarian obstetric units from 2000-2007 were extracted from a standard dataset for which data are regularly collected for the national benchmarking of obstetric units. METHODS: We calculated the odds ratios (ORs) for adverse pregnancy outcome by GWL (explanatory variable) compared with nonexcessive weight gain with adjustment for confounders and stratification by BMI category (underweight, BMI < 18.5 kg/m²; normal weight, BMI = 18.5-24.9 kg/m²; overweight, BMI = 25-29.9 kg/m²; obese class I, BMI = 30-34.9 kg/m²; obese class II, BMI = 35-39.9 kg/m²; obese class III, BMI ≥ 40 kg/m²). MAIN OUTCOME MEASURES: Pre-eclampsia, nonelective caesarean section, preterm delivery, small or large for gestational age (SGA/LGA) birth and perinatal mortality. RESULTS: GWL was associated with a decreased risk of pregnancy complications, such as pre-eclampsia and nonelective caesarean section, in overweight and obese women [e.g. OR = 0.65 (95% confidence interval: 0.51, 0.83) for nonelective caesarean section in obese class I women]. The risks of preterm delivery and SGA births, by contrast, were significantly higher in overweight and obese class I/II mothers [e.g. OR = 1.68 (95% confidence interval: 1.37, 2.06) for SGA in obese class I women]. In obese class III women, no significantly increased risks of poor outcomes for infants were observed. CONCLUSIONS: The association of GWL with a decreased risk of pregnancy complications appears to be outweighed by increased risks of prematurity and SGA in all but obese class III mothers.

Improvement in pregnancy-related outcomes in the offspring of diabetic mothers in Bavaria, Germany, during 1987-2007.

AIMS: Reducing the risk of adverse outcomes in diabetic pregnancies to the level of risk in non-diabetic pregnancies is a major goal in diabetes care. So far there have not been any data to show whether progress is being made towards this goal. METHODS: We used population-based data on 2,292,053 deliveries between 1987 and 2007 in Bavaria, Germany, to assess temporal trends for stillbirths, early neonatal mortality, preterm delivery, macrosomia and malformations in consecutive 7 year intervals. We estimated prevalences and prevalence odds ratios for these outcomes. For stillbirth, as the most severe adverse outcome, we assessed the contributions of several predictors using multiple regression models. RESULTS: With the exception of early neonatal deaths, the risks for all outcomes were significantly increased in the offspring of mothers with pregestational diabetes in all three time periods (e.g. odds ratio for stillbirths in diabetic compared with non-diabetic mothers in 2001-2007, 1.89; 95% confidence interval 1.24, 2.87). However, the prevalence of stillbirths, premature delivery and macrosomia decreased over time in diabetic mothers (e.g. 1.71% for stillbirths in 1987-1993 and 0.66% in 2001-2007), as did the respective odds ratios. Maternal smoking, hypertension and substandard utilization of antenatal care were significantly associated with stillbirths in diabetic women. CONCLUSIONS: Although the risk of adverse pregnancy outcomes is still increased in diabetic mothers, considerable improvement has been achieved. We hypothesize that this improvement is possibly due to improved diabetes care.

[Social differences in the utilisation of prenatal screening, smoking during pregnancy and birth weight--empirical analysis of data from the Perinatal Study in Bavaria (Germany)]. / Soziale Unterschiede bei der Inanspruchnahme der Schwangerschafts-Vorsorgeuntersuchungen, beim Rauchen der Mutter während der Schwangerschaft und beim Geburtsgewicht des Neugeborenen. Empirische Analyse auf Basis der Bayerischen Perinatal-Studie.

INTRODUCTION: Perinatal studies provide an excellent database for public health research, to date this potential has rarely been used, however. Taking the example of the Perinatal Study in Bavaria, the objective is to demonstrate the pros and cons of this database. As it includes only very few variables on socio-economic status, an additional variable is calculated assessing the socio-economic status of the community where the mother lives. This is rarely done in Germany, and as far as we know the procedure proposed here has not been applied before. METHODS: The analyses are based on the data from 2004. They focus on three dependent variables: number of prenatal screenings, maternal smoking during pregnancy, birth weight of the baby. The following independent variables are included as well: age of the mother, nationality of the mother (e.g., German, Mediterranean countries), single mother (yes/no), occupational status of the mother, community where the mother lives (4- or 5-digit postal code). The socio-economic status of the community is assessed by the poverty rate, linking two other datasets, one for transferring the postal codes to community names, the other providing information per community. The multivariate analyses are conducted by logistic regressions. RESULTS: Information was available from about 76 000 births. Concerning the variable 'few prenatal screenings', the analyses show an increased risk for mothers from Eastern Europe and from the Mediterranean countries, for single mothers and for mothers with low occupational status. The risk factor 'maternal smoking during pregnancy' is increased for mothers from the Mediterranean countries and for single mothers. It is especially high, however, for low status blue collar workers: compared with white collar workers their smoking prevalence is 4.67-times (large cities) or even 6.14-times (smaller communities) higher. The risk factor 'low birth weight of the baby' is again increased for single mothers and for mothers with low occupational status. An association with the poverty rate is mainly seen for the variable 'maternal smoking during pregnancy', with higher smoking prevalences in the poor communities. DISCUSSION: The results demonstrate that the data from the perinatal studies are important for public health research. Concerning the risk factors analysed here, large social differences can be observed. In order to show time trends, it would be important to repeat these analyses on a routine basis. From a methodological point of view, it can be stressed that regional differences in health and health care have rarely been looked at in Germany, and that the procedure proposed here provides a new starting point for closing this research gap.

A pharmacokinetic-pharmacodynamic model for the mobilization of CD34+ hematopoietic progenitor cells by AMD3100.

BACKGROUND: AMD3100 is a small-molecule CXCR4 antagonist that has been shown to induce the mobilization of CD34 + hematopoietic progenitor cells from bone marrow to peripheral blood. AMD3100 has also been shown to augment the mobilization of CD34 + cells in cancer patients when administered in combination with granulocyte colony-stimulating factor (G-CSF) (filgrastim). The purpose of this study was to characterize the exposure-response relationship of AMD3100 in mobilizing CD34 + cells when administered as a single agent in healthy volunteers. METHODS: AMD3100 concentrations and CD34 + cell counts obtained from 29 healthy subjects in a single-dose, intensively sampled pharmacokinetic/pharmacodynamic (PK-PD) study were analyzed by use of nonlinear mixed effects regression with the software NONMEM. FOCE (first order conditional estimation) with interaction was the estimation method, and simultaneous PK-PD fitting was adopted. RESULTS: The pharmacokinetics of AMD3100 was described by a 2-compartment model with first-order absorption. The population estimates (+/-SE) for clearance and central volume of distribution were 5.17 +/- 0.49 L/h and 16.9 +/- 3.79 L, respectively. CD34 + cell mobilization was best described by an indirect effect model that stimulates the entry process of CD34 + from bone marrow to peripheral blood in the form of a sigmoid maximum effect model. The population estimates (+/-SE) of maximum effect, concentration causing 50% of maximum response, and equilibration time were 12.6 +/- 4.89, 53.6 +/- 11.9 mug/L, and 5.37 +/- 1.31 hours, respectively. CONCLUSIONS: This study characterizes the exposure-response relationship of AMD3100 in mobilizing CD34 + cells after subcutaneous administration. This PK-PD model will be useful in assessing relevant covariates and for optimizing the use of AMD3100 in various patient populations.

GerOSS (German Obstetric Surveillance System). A Project to Improve the Treatment of Obstetric Rare Diseases and Complications Using a Web Based Documentation and Information Platform.

BACKGROUND: Severe and very rare obstetric complications (e.g. eclampsia, postpartum haemorrhage or uterine rupture), typically culminate in a chaotic, uncontrollable sequence of events. Outcome for mother and child depends on whether doctors and midwives are able to quickly take correct decisions and initiate optimal treatment. OBJECTIVES: GerOSS (German Obstetric Surveillance System) aims at generating deeper insight into relevant risk factors to improve diagnosis and treatment of severe complications during pregnancy and delivery. As such it is primarily conceived as a system for quality improvement and less as a register. Another focus is the provision of an information and communication platform for dissemination of these insights. Finally, incidences of selected rare obstetric events may be derived. METHODS: These rare events are monitored for two to five years in Lower Saxony, Bavaria and Berlin. Quantitative analyses of aggregate data are complemented with in depth case based anonymised evaluations by experts. The temporal sequence of measures taken as well as the management of care is inspected. Participants receive a feedback of comments on the synopsis of individual cases. Aggregate data results are published and made available through the GerOSS platform. A scientific advisory committee ensures the link with the professional scientific bodies. A comparison within INOSS (International Network of Obstetric Survey Systems) allows additional insights into the treatment of obstetric rare diseases and complications. More reliable estimates of the incidence of such events can be computed and compared within a larger database. RESULTS: Following the implementation in three federal states in Germany in 2010, participation in GerOSS-Project has increased to 100% of all hospitals with a delivery unit in Lower Saxony, 30% in Bavaria and 80% in Berlin. Feasibility of the project is shown by successful implementation of GerOSS. Quantitative analyses enable construction of risk profiles (e.g. for the prevalence of hysterectomies and uterine ruptures) such that tailored treatment algorithms may be derived. Age, body mass index and previous caesarean section are common risk factors when complications occur. Respective recommendations have not always been adhered to in the diagnosis and therapy of such cases. The presentation of initial GerOSS results has paved the path for first changes in obstetric care. CONCLUSIONS: The envisaged expansion of GerOSS to an interactive platform will allow dissemination of insights such that optimal obstetric care and transferal among all involved medical facilities may see future enhancements via the internet or even through smartphone applications.

[Federal admission criteria for levels of perinatal care: definition, interpretation and first conclusions]. / Aufnahmekriterien nach dem G-BA-Beschluss: definition, interpretation und erste schlussfolgerungen.

BACKGROUND: The outcome of high risk pregnancies is better in tertiary hospitals. The German government introduced levels of perinatal care only in 2006. The aim of this study was to investigate how many children are to be expected for each level, taking the possible width of interpretation of the admission criteria into account. MATERIALS AND METHODS: Perinatal quality assurance data from four German states (2005) were available. Based on the admission criteria used for level definitions, children were categorised into four different levels of care. To illustrate the possible width of interpretation of these admission criteria three analytical strategies were used. In addition, the distribution of children on different types of hospitals prior to the introduction of levels of care was analysed. RESULTS: Most deliveries (86-93 %) correspond to the lowest level, and only 1-5 % to the highest. Up to 15 % of children who should have been cared for in the highest level were born in hospitals with less than 500 annual deliveries. Among the neonates with risk profiles corresponding to the admission criteria for the two highest levels, up to 30 % were born in delivery units without NICUs. The majority (83 %) of attached NICUs had low caseloads (< 50 neonates < 1500 g / year). CONCLUSION: Most children fulfil the admission criteria for the lowest level of care whereas the need for specialised centres is rather low. Optimising the place of birth appropriately remains a challenge. Definition of levels of care based on admission criteria are difficult to implement due to a broad variety of interpretations.

[Quality measurement between illusion and reality--is the quality of medical care measurable?]. / Qualitätsmessung zwischen Illusion und Realität -- Ist Qualität in der Medizin messbar?

The current implementation of external quality assurance focuses on identical, albeit simple univariate procedures. This approach proves to be inefficient, exhibiting low specificity. Definitions of performance indicators were classified by the local steering committee and applied to Bavarian obstetric data augmented with multivariate and confidence interval analyses as well as statistical simulations. A highly selected group of units with multivariate extreme values was audited. Blind application of federal regimes without further in-depth analysis of concomitant data is inefficient and may lead to wrong conclusions. Exclusive univariate analyses of performance indicators are not enough. Multivariate analyses have a higher specificity. Classification reveals an imbalance in the indicator set with respect to varying degrees of coverage as well as a bias towards outcome. Deficiencies in the organisational processes crucial for quality of care are often only revealed by dedicated cause and effect analyses within the hospital, thus constituting an essential prerequisite for desired changes in health care policies. It is unlikely that mere publication of performance indicators in the impending quality report will generate lucidity in spite of abundant structure. The installation of standardised programmes with identical computation rules may appear convincing as long as no doubt is cast upon the efficacy of the performance indicators in respect to their intended usage as well as upon the expected feedback effects. The experience so far however teaches us that these elements may be essential yet although not sufficient.

Comparison of non-invasive sampling methods for detection of HPV in rural African women.

BACKGROUND: The prevalence of cervical cancer is extremely high in low income countries, primarily because of a lack of cytological screening. The link between human papillomavirus (HPV) and cervical cancer has long been recognised, and it has been suggested that isolated HPV testing in women who do not participate in existing screening programmes may be used to identify women at higher risk of developing cervical cancer. This community based study compares two self administered techniques for detecting HPV (tampons and self administered swabs) with a clinician directed technique, the cervical cytobrush. METHODS: 377 rural women were interviewed and of these 210 women had full gynaecological examination, and accepted all three sampling methods for HPV. HPV typing of DNA extracts was performed using polymerase chain reaction and enzyme linked immunosorbent assay techniques. RESULTS: Using the cervical cytobrush as the gold standard, self administered swabs (SAS) showed a sensitivity of 63.9%, and tampons showed a sensitivity of 72.4%. The acceptability of these two tests was 97.1% and 84.6% respectively. When combining acceptability with sensitivity, the SAS detected 61.9% and the tampons detected 60.9% of the true positives. CONCLUSION: In a setting where women are at a considerable risk of developing cervical cancer, with no access to a formal screening programme, self directed HPV testing could be a useful screening tool in identifying those women at increased risk who may require further investigation.

[Current developments in the German Perinatal Survey. Modular analysis tools operating on a database platform]. / Aktuelle Entwicklungen bei der Perinatalerhebung - Modulares Datenbank-gestütztes Auswertungsmodul -

The introduction of the modified data set for quality assurance in obstetrics (formerly perinatal survey) in Lower Saxony and Bavaria as early as 1999 saw the urgent requirement for a corresponding new statistical analysis of the revised data. The general outline of a new data reporting concept was originally presented by the Bavarian Commission for Perinatology and Neonatology at the Munich Perinatal Conference in November 1997. These ideas are germinal to content and layout of the new quality report for obstetrics currently in its nationwide harmonisation phase coordinated by the federal office for quality assurance in hospital care. A flexible and modular database oriented analysis tool developed in Bavaria is now in its second year of successful operation. The functionalities of this system are described in detail.