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J. Perinat. Med. 39 (2011) 257265 Copyright by Walter de Gruyter Berlin New York. DOI 10.1515/JPM.2011.010

Risk groups and maternal-neonatal complications of preeclampsia Current results from the national German Perinatal Quality Registry

Sven Schneider1,2,a,*, Nele Freerksen3,a, Holger Maul4,a, Silke Roehrig2, Burkhard Fischer5 and Birgit Hoeft1,a
1

Mannheim Institute of Public Health, Social and Preventive Medicine (MIPH) Mannheim Medical Faculty, Heidelberg University, Ludolf-Krehl-Str. 7-11, D-68167 Mannheim, Germany 2 Competence Center for Social Medicine and Occupational Health Promotion, Heidelberg University, Ludolf-KrehlStr. 7-11, D-68167 Mannheim, Germany 3 University Womens Hospital of the RWTH Aachen, Aachen University, Pauwelsstr. 30, D-52074 Aachen, Germany 4 Womens Hospital, Katholisches Marienkrankenhaus, Alfredstr. 9, D-22087 Hamburg, Germany 5 German Federal Agency for Quality Assurance gGmbH, Du sseldorf, Kanzlerstr. 4, D-40472 Du sseldorf, Germany

Conclusions: Further studies and interventions regarding prenatal care should not focus only on how better diagnostic and treatment procedures can be implemented but also on how these diagnostic and treatment procedures can reach high-risk groups. Keywords: Abnormalities; gestational diabetes; gestosis; hypertension; preeclampsia; pregnancy complications; proteinuria; risk factors.

Introduction
Preeclampsia is a leading cause of serious complications during pregnancy. Prevalence rates of preeclampsia in developed countries range from 3% to 8% among all pregnancies w 2, 4, 13, 15, 24x with reoccurrence rates of 1318% w 9x . As preeclampsia accounts for about 42% of all maternal deaths w 5, 25x increasing research efforts to investigate this serious condition have been made within the last years. Preeclampsia is characterized by systemic endothelial dysfunction resulting in elevated blood pressure and proteinuria. Maternal complications include eclampsia (onset of seizures), renal failure, placental abruption, stroke, major complications like infections, and maternal mortality w 2, 4, 13, 15, 24x . Fetal problems include stillbirths, neonatal mortality, intrauterine growth restriction (IUGR) and complications due to preterm delivery caused by exacerbated preeclampsia w 14x . Despite intensive research, the causes of preeclampsia still remain uncertain. Recent studies have found that angiogenic factors, insulin-resistance and changes in the renin-angiotensin system might be partially responsible for the pathogenesis of the disease w 13x . Because the etiology is still unclear, it is not surprising that no effective screening methods for the prediction of preeclampsia have been developed. Although various clinical trials have evaluated different modes of therapy, currently no effective preventive or therapeutic measures have been found aside from immediate delivery of the fetus. The absence of successful therapeutic measures calls for further research. Sound knowledge of the relevant risk factors is necessary to develop effective screening methods. In this context, research has focused on various topics, such as the relationship between gestational diabetes, pre-existing obesity, increased maternal weight gain and preeclampsia in the last few years w 3, 4, 6, 11, 15, 16, 20, 21, 23, 24, 26x . The role of parity w 15, 26x and of multiple pregnancies w 4x has also been examined by various authors. So far, the findings of the influence of maternal age during pregnancy w 10, 21, 26x and tobacco consumption w 15, 21, 26x are contradictory. Additionally, there is a surprising lack of research on

Abstract
Aims: We investigated risk factors and neonatal outcomes of preeclampsia. Methods: We analyzed data of the German Perinatal Quality Registry 2006 that contains the complete national birth cohort of 668,085 newborn infants and 647,392 mothers from 917 German obstetric clinics. Results: The prevalence of preeclampsia in 2006 was at 2.31%. Higher maternal age, gestational diabetes, no previous as well as multiple births, pre-pregnancy obesity and above-average weight gain during pregnancy were significantly associated with preeclampsia. A positive relationship between social burden (e.g., low social status, psychosocial stress) and the risk of preeclampsia appeared. Smoking appeared to be negatively correlated. Neonatal complications associated with preeclampsia in the study were small babies, acute respiratory distress syndrome, postpartum neonatal hypoglycemia and low Apgar scores. We did not observe an increased rate of stillbirths with preeclampsia pregnancies.
Authors contributed to this paper equally. *Corresponding author: Sven Schneider, Prof., Dr., MA Mannheim Institute for Public Health Social and Preventive Medicine (MIPH) Medical Faculty Mannheim Heidelberg University Ludolf-Krehl-Str 7-11 D-68167 Mannheim Germany Tel.: q49-621-383-9917 Fax: q49-621-383-9920 E-mail: sven.schneider@medma.uni-heidelberg.de
a

2010/096

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258 Schneider et al., Risk groups and outcomes of preeclampsia

the influence of social risk factors (e.g., low socio-economic status, psychosocial stress and drug abuse). Our study aims to add further knowledge to current research. Specifically, we intend: 1. to investigate the importance of the above-mentioned risk factors (especially factors that have scarcely been investigated and those with contradictory results) and, 2. to study the impact of preeclampsia on the fetal, neonatal and maternal outcomes.

Methods
Our study was the first to use data from the German Perinatal Quality Registry. This national registry contains complete birth cohort data and information that can be used for identifying high-risk groups and evaluating current screening options. It is a full inventory of all hospital births in Germany. The Registry is part of a standardized national medical and nursing quality assurance program for German hospitals. The program was set up in 2001 with the involvement of the governing bodies of the Statutory Health Insurance System, the Association of German Private Health Insurance companies, the German Hospital Association, the German Medical Board and Long-Term Nursing Care Insurance organizations w 8x . One of the core areas covered in this healthcare quality assurance system is obstetrics and gynecology. The German Federal Agency for Quality Assurance (Bundesgescha ftsstelle Qualita tssicherung gGmbH BQS) collects detailed data and quality indicators for all hospital deliveries in a given calendar year on behalf of the aforementioned organizations. These data are made available in the German Perinatal Quality Registry w 8; see also Attachment at the end of this articlex . This is possible, because in Germany, the prenatal care during pregnancy offered by health insurance organizations is nationally standardized. Over 95% of all pregnant women submit a maternity log (Mutterpass) prior to giving birth. The majority (98.3%) of all pregnant women attend at least five of the regular examinations at their obstetricians practices w 7x . These examinations are conducted using clear, nationally standardized guidelines, which also include guidelines for further courses of action should any symptoms of preeclampsia appear. For example, blood pressure should be measured and a test for proteinuria carried out during each of the regular examinations. In accordance with the quality guidelines, each case should be registered in the maternity log and recorded in the Perinatal Quality Survey. As reporting is mandatory for all deliveries, perinatal data are available for 99.3% of births in Germany w 8x . The current German Perinatal Quality Registry 2006 contains pre- and perinatal data on 668,085 newborn infants and 647,392 mothers from all 917 German obstetric clinics. Approval for the study was received from the University of Heidelberg Ethics Committee (protocol number AZ S165/2008). The database on obstetrics and gynecology includes information on maternal sociodemographic factors and anamnestic maternal data. To assess the influence of potential risk factors we adopted a research design similar to a recent publication w 26x and included all of their risk factors as well as additional variables of our interest (social status and stress indicators, alcohol and drug abuse, and multifetal pregnancies). The selection of potential risk factors has also been approved by the panel of experts of the German Federal Agency for Quality Assurance and the Federal Joint Committee. Social status was evaluated using employment status prior to pregnancy. Nom-

inal categories were used to label non-working women: housewives, trainees, and students. Ordinal categories were used to rank the employment status prior to pregnancy: unskilled worker, skilled worker, higher service/management. The social burden of pregnant women included self-reports of psychosocial stress from work or home. Drug abuse and average daily cigarette consumption was measured after pregnancy confirmation. Data regarding weight at first antenatal visit, weight gain during pregnancy, number of prior pregnancies (including stillbirths and terminations) and multiple births were also collected. The data was derived from maternity log books, which are given to all women in Germany as soon as the primary-care gynecologist confirms pregnancy. Information is regularly entered into the maternity log during subsequent prenatal examinations throughout pregnancy in a standardized fashion. Obstetric and neonatological outcomes are added to the log during the first few postpartum days and prior to discharge from the clinic. If the primary-care gynecologist or physician in the obstetric clinic diagnoses preeclampsia, this diagnosis is also registered in the maternity log. In addition, all pregnancies with a simultaneous diagnosis of hypertension (repeatedly )140/90) and proteinuria are routinely coded as cases of preeclampsia in the German Perinatal Quality Registry. According to standard coding procedures, all cases with a diagnosis of HELLP syndrome were coded as a variant of preeclampsia. Diagnoses of gestational diabetes were recorded as well (e.g., as a pregnancy risk or flagged as indicator for hospital admission). In accordance with standard procedures w 15x , pre-existing cases of diabetes mellitus were excluded. German law (PersStdGAV29) defines a stillbirth as a newborn with no signs of life (no heartbeat, no breathing movements, no umbilical pulsations) and a birth weight of at least 500 g. Sex stratified small-for-gestational age (SGA) was coded as birth weight under the 10th percentile for gestational age. Hypertension, proteinuria, fetal malformations, type of delivery, birth weight of the child, diagnoses of macrosomia, hypoglycaemia, acute respiratory distress syndrome (ARDS), neonatal convulsions, and other relevant neonatal outcomes were defined according to the International Statistical Classification of Diseases and Related Health Problems (ICD 10). In the first step, x2-testing was employed to determine the relationship between the categorical variables of interest by comparing observed frequencies in the normal population to frequencies in the preeclampsia categories. In the second step, logistic regression models were used to estimate the odds ratios (OR) and corresponding 95% confidence intervals (95% CI) for the purposes of identifying the separate contribution of several risk factors (preeclampsias1, no preeclampsias0). ORs were calculated for each potential determinant (unadjusted ORs; Model 1). All variables were then included in a single multivariate adjusted model (adjusted ORs; Model 2). All P-values reported are two-tailed with significance level of P-0.05. All statistical analyses were done using SPSS version 16.0. (SPSS Inc., Chicago, IL, USA).

Results
In Germany, the prevalence of preeclampsia was 2.31% (14,934/647,385) among all pregnant women in 2006. Highrisk groups for the development of preeclampsia were older, nulliparous, non-smoking women as well as women with low socioeconomic status, psychosocial stress, a history of drug abuse and multiple gestations. Preeclampsia was also associated with gestational diabetes, pre-pregnancy obesity and an above-average weight gain during pregnancy (Table 1).

Table 1 Bivariate analyses and multiple logistic regression analyses for correlates of preeclampsia during pregnancy in Germany. n (Preeclampsia) -0.001 336 2193 4260 4269 3876 1.361x 1.386x 1.340x 1.569x Reference 0.846 w 0.778, 0.920x 0.711 w 0.635, 0.795x 0.720 w 0.674, 0.770x 1.355x 1.218x 1.070x 1.120x Reference 1.227 w 1.125, 1.337x 0.677 w 0.630, Reference 1.828 w 1.750, 3.190 w 3.031, 5.768 w 5.470, -0.001 9770 2259 855 424 10,855 441 373 308 14,490 444 2.3 2.1 1.5 1.6 -0.001 2.3 1.6 Reference 0.688 w 0.626, 0.757x Reference 0.929 w 0.782, 1.048x 0.231 1.9 3.6 5.6 8.6 -0.001 Reference 1.025 w 0.934, 1.124x 0.985 w 0.904, 1.073x 0.869 w 0.787, 0.960x Reference 0.866 w 0.785, 0.957x 0.632 w 0.566, 0.706x 0.724 w 0.633, 0.828x 0.005 -0.001 -0.001 Reference 1.907 w 1.820, 1.998x 3.013 w 2.805, 3.238x 4.731 w 4.274, 5.237x Reference 1.926 w 1.836, 2.021x 2.848 w 2.645, 3.066x 4.082 w 3.675, 4.534x -0.001 -0.001 -0.001 0.728x 1.909x 3.357x 6.083x 0.704 w 0.655, Reference 1.943 w 1.859, 3.675 w 3.489, 7.079 w 6.699, 0.756x 2.030x 3.871x 7.480x 1.350x 1.450x 1.584x 2.065x -0.001 12,968 607 325 1034 -0.001 612 5297 1731 401 4139 0.960x 0.880x 0.003 14,358 576 -0.001 1947 4779 3632 2257 2094 1.1 1.7 2.8 4.8 8.4 -0.001 -0.001 -0.001 -0.001 2.3 2.6 Reference 1.138 w 1.046, 1.238x -0.001 2.9 2.8 2.2 1.9 1.9 1.301 w 1.185, 1.232 w 1.166, Reference 0.861 w 0.771, 0.832 w 0.786, 1.428x 1.301x 1.230 w 1.117, 1.152 w 1.089, Reference 0.953 w 0.849, 1.053 w 0.991, -0.001 -0.001 0.415 0.098 1.6 1.5 0.623 w 0.557, 0.696x 0.608 w 0.571, 0.649x 2.5 1.8 Reference 0.713 w 0.657, 0.775x -0.001 -0.001 -0.001 1.8 2.2 2.3 2.2 2.6 Reference 1.212 w 1.079, 1.239 w 1.108, 1.198 w 1.071, 1.402 w 1.253, Reference 1.198 w 1.063, 1.289 w 1.145, 1.406 w 1.248, 1.831 w 1.623, 0.003 -0.001 -0.001 -0.001 % (Preeclampsia) P-valuea Model 1 ORb w 95% CIx Model 2 OR adjustedc w 95% CIx Significance for Model 2

Variable

n (total)

18,175 98,264 186,818 193,453 150,676

524,289 34,154

20,906 68,036

21,079 192,366 77,036 20,671 220,653

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625,266 22,119

84,400 305,438 128,644 46,776 24,933

501,673 61,904 15,140 4936

Aged -20 years 2025 years 2530 years 3035 years )35 years Nationality German Eastern Europe (former Eastern bloc) Mediterranean neighbour Other nationalities Job status Unskilled workere Skilled worker, middle servicee Higher service/managemente Trainee, studentf Houswifef Social or psychological impactsg No Yes BMIg -20 2025 2530 3035 )35 Weight gain during pregnancy -20 kg 2025 kg 2530 kg )30 kg Smoking Non-smoker 15 cigarettes/day 610 cigarettes/day )11 cigarettes/day Alcohol and/or drug abuse No Yes

462,196 20,480 24,808 18,857

Schneider et al., Risk groups and outcomes of preeclampsia 259

619,991 27,394

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260 Schneider et al., Risk groups and outcomes of preeclampsia

Significance for Model 2

(Table 1 continued)

Number of pregnancies First pregnancy Further pregnancy Multifoetal pregnancies No Yes Gestational diabetes mellitus No Yes Number of pregnant women (n)

Dependent variable: Preeclampsias1, ORsodds ratio, 95% CIs95% confidence interval. a 2 x -test; bUnadjusted ORs; cAdjusted for all variables; dAge at delivery; eOrdinal categorization; fNominal categorization; gkg/m2.

The risk of developing preeclampsia increased with age. Compared to a prevalence of 1.8% among women -20 years of age, the prevalence was 2.6% for women )35 years. After adjusting for confounders, ORs increase almost linearly up to 1.831 for the oldest pregnant women. Immigrants showed a significantly decreased risk of preeclampsia compared to German women (Table 1). An association was also found with socioeconomic status: women with low-income jobs were diagnosed with preeclampsia more frequently than pregnant women with high-income jobs (i.e., executive positions or positions requiring a university degree). Pregnant women reporting particularly high social stress also showed a higher risk of preeclampsia. Whereas alcohol or drug abuse did not alter the risk of preeclampsia, minor and major tobacco consumption were associated with a lower risk. Compared to singleton gestations, multiple gestations were related to an increased risk of developing preeclampsia. The data set also permitted investigations into the relationship between weight, weight gain, gestational diabetes and preeclampsia. The relationship between preeclampsia and pre-pregnancy body weight as well as weight gain seems to be linear. In bivariate comparisons, women with an initial body mass index (BMI) )35 and women with a weight gain of more than 30 kg showed significantly higher rates of preeclampsica (8.4% and 8.6%, respectively). Gestational diabetes was also associated with a higher preeclampsia risk. If these three factors are taken into account within an adjusted model, it becomes clear that 1) the ORs remain significant when all other factors remain constant, and 2) BMI plays a key role in the etiology of the disease (Table 1, Model 2). Preeclampsia increases the risk of several complications. The risk of SGA was 15.1 in preeclampsia cases compared to 4.1 in non-cases, per thousand deliveries (P-0.001). Analyzed in more detail, preeclampsia led more often to low birth weights and less often to above-average birth weights in both male and female neonates (P-0.001; Table 2). Low Apgar scores were further important complications during pregnancy and delivery. These complications also occured significantly more often among preeclampsia pregnancies (P-0.001; Table 2). For preeclampsia pregnancies the rate of fetal malformation did not differ significantly. Furthermore, preeclampsia was associated with a lower rate of stillbirths (P-0.001; Table 2). Additional analyses showed that the rates of ARDS (0.37% vs. 0.11%) and the risk of postpartum neonatal hypoglycaemia (0.66% vs. 0.26%) were also significantly higher among the preeclampsia cases (P-0.001). The rate of primary cesarean sections was three times as high and the rate of secondary section twice as high compared to those without preeclampsia (P-0.001).

-0.001

-0.001

Model 2 OR adjustedc w 95% CIx

Reference 0.434 w 0.417, 0.451x

Reference 2.284 w 2.098, 2.486x

Reference 0.481 w 0.464, 0.498x

Reference 2.755 w 2.537, 2.991x

P-valuea

Model 1 ORb w 95% CIx

-0.001

-0.001

% (Preeclampsia)

2.2 6.0

-0.001 14,306 628 636,837 10,548 632,395 14,990 647,385 14,322 612 14,934 2.3 4.1 2.3

n (Preeclampsia)

n (total)

321,563 325,822

9989 4945

3.1 1.5

Reference 1.837 w 1.691, 1.995x

Reference 1.294 w 1.188, 1.409x

-0.001

Discussion
The results demonstrate that the overall prevalence of preeclampsia in Germany is low (2.31%) but that certain groups are at higher risk. Risk factors for preeclampsia are higher maternal age, lower social status, psychosocial stress, no pri-

Variable

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Table 2 Outcome in children in regard to the independent variable preeclampsia. Outcome variable (dependent variable) Birth weight -10% percentile: Preeclampsia No preeclampsia Birth weight )90% percentile: Preeclampsia No preeclampsia 5-min Apgar score -7: Preeclampsia No preeclampsia Fetal malformation: Preeclampsia No preeclampsia Stillbirth: Preeclampsia No preeclampsia n n Model 1 Crude odds ratio for preeclampsia w 95% CIx 1.902 w 1.820, 1.989x Reference 0.925 w 0.877, 0.976x Reference 2.271 w 2.039, 2.529x Reference 0.921 w 0.777, 1.093x Reference 0.645 w 0.449, 0.925x Reference Model 2 Adjusted odds ratio for preeclampsia w 95% CIx 2.077 w 1.984, 2.174x Reference 0.789 w 0.747, 0.834x Reference 2.083 w 1.876, 2.325x Reference 0.908 w 0.764, 1.078x Reference 0.598 w 0.416, 0.860x Reference

Yes 2407 58,022 Yes 1531 69,465 Yes 356 6746 Yes 136 6246 Yes 30 6246

No 12,527 574,429 No 13,403 562,986 No 14,487 623,353 No 14,798 626,205 No 14,904 626,205

or as well as multiple births, pre-pregnancy obesity, aboveaverage weight gain during pregnancy and gestational diabetes. Smoking appears to be negatively correlated with preeclampsia. Neonatal complications are SGA, ARDS, postpartum neonatal hypoglycemia as well as low Apgar scores. In contrast to other countries, our results for Germany did not show an increased rate of stillbirths from preeclampsia pregnancies. The four most important limitations of this nationwide, register-based study are undetected cases, missing data and values, validity of self reports, and lack of causality. It is expected that a certain number of preeclampsia cases go unreported every year. With regard to the interpretation of the results, it is important to consider that pregnant women with preeclampsia receive treatment once they are diagnosed. Any assumptions regarding the negative effects of preeclampsia that are based on the reported effect size are therefore possibly underestimating the true effects. Due to limited data access, not all possible maternal and fetal outcomes could be included. Therefore, no analyses were conducted, among others, on the influence of the date of diagnosis or the number of prenatal consultations, or concerning major complications like renal failure, placental abruption or maternal or neonatal mortality. As data on all pregnancies is collected systematically in the national registry, little relevant information was missing for the included variables. While the so-called mandatory fields were almost complete (-1% missing values), data from the optional information sections were more frequently missing. The rates of missing data were 5.5% for BMI, 16.2% for occupation and 19.6% for tobacco consumption. In order to deal with this missing information, we included the category missing data in our regression model. This helped to avoid a reduction in the total number of cases and to maintain the representativeness of the remaining associations. A desire to give socially approved responses can result in under-reporting of smoking prevalence and drug abuse during pregnancy. This potential social desirability

bias was discussed recently w 17, 18x . Current literature puts the extent of under-reported smoking among pregnant women at 35% points. Due to the observational design of our study, we cannot conclude that preeclampsia is causally related to the risk factors and adverse outcomes. However, the discussed relationships are plausible. The Bradford-Hill Criterion of dose-response relationships (i.e., age, BMI and smoking) is also met. The Perinatal Quality Survey provides well-characterized and (nearly) complete cohort information. Preeclampsia cases are diagnosed within a standardized health care and quality controlled system where more than 98% of women access prenatal care, ensuring the consistency and validity of the diagnostic outcome information w 7x . The broad coverage of the registry and the large number of pregnancies included, are important strengths of our study. Information is lacking only for out-of hospital births (births in midwives clinics or home births), which amount to approximately 10,000/year (i.e., -1.5%; w 12x ). The German preeclampsia prevalence rate of 2.3% is lower than the rates from other countries (38%) w 2, 4, 13, 15, 24x . As described in detail above, Germany is a country where more than 98% of all pregnant women receive highly standardized prenatal care. This may explain why the rates of preeclampsia (and the rate of consecutive stillbirths) in Germany are much lower compared with other countries. The Mutterpass (maternity log) that is distributed to all pregnant women thus could serve as a model for other national prevention programmes. In Germany, prevalence rates for preeclampsia are low, yet the risk is not distributed equally over all social classes. The risk is higher among certain groups. With regard to some of the risk factors examined in this study, the results of our statistical analyses confirm the findings of other authors w 3, 4, 6, 11, 15, 16, 1921, 23, 24, 26x . For example, we also found that primiparity as well as multiple births, pre-pregnancy obesity, above-average weight gain during pregnancy

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262 Schneider et al., Risk groups and outcomes of preeclampsia

and gestational diabetes resulted in a higher risk of preeclampsia. We were also able to replicate the findings showing that GDM and obesity were important independent risk factors for preeclampsia. The ORs we found equal those of other authors w 6, 15x . Whereas fetal macrosomia itself, when defined as a birth weight over the 90th percentile, is negatively correlated with preeclampsia in our study, babies of mothers with gestational diabetes are obviously too large relative to the placental potential (Table 1). One may also hypothesize that gestational diabetics exhibit a vascular profile that may enhance the development of preeclampsia as a vascular reactivity disorder, as postulated by many authors. Another important finding for future preventive measures is the relationship between social burden (e.g., low social status, psychosocial stress, and drug abuse) and the risk of preeclampsia, an aspect that has rarely been investigated. These factors are associated with an unhealthy lifestyle, metabolic syndrome and fewer prenatal care visits w 1, 17, 18, 22x . This aspect of health inequality will not be ameliorated in the future if socially disadvantaged women are not reached effectively. Our data support the need for developing such strategies in order to reduce the rates of preeclampsia. At the same time that Sibai et al. w 21x did not find a significant effect with age, Krapp w 10x reported a higher risk for younger pregnant women. Conversely, Wendland et al. w 26x showed an increased risk with age. Our data support the same linear relationship. Smoking as a risk factor for preeclampsia has been studied with mixed findings. Apart from our analysis, Wendland et al. w 26x and Sibai et al. w 21x found no effect. In contrast, smoking as a negatively correlated factor has also been found stlund et al. w 15x . Smoking may both alter in the study of O vascular reactivity during gestation and hinder growth thereby reducing the fetal need for oxygen and nutrients and decreasing the risk of preeclampsia. It is important to point out that smoking is not a strategy for prevention due to the many other effects it has on maternal and neonatal health as well as its association with other adverse maternal and fetal morbidity w 18x . It is important to note the complex relationship between sociostructural and behavior-related variables in this context (such as age, social status, nationality and smoking). German nationality has so far been associated with a higher social status and higher age at delivery. Besides, smoking during pregnancy is less common among non-German, higher educated as well as older women w 17, 18x . These confounding phenomena are addressed and partially controlled for in the multiple logistic regression analysis (Table 1). Further analyses of complex interaction effects were beyond the scope of the study and data availability. Future studies should therefore account for such interaction effects and include additional variables, such as the date of diagnosis and prenatal health care use. Although our findings seem to be partially contradictory in the first place (smoking, stillbirths) they fit together very well supporting the theory that preeclampsia may be the result of an impaired relationship between offer and demand. Preeclampsia therefore is associated with low birth weight

babies. Their strategy to survive seems to be the signal to the mother to increase blood pressure at the point when placental function is no longer sufficiently promoting fetal growth. Increase in blood pressure enhance placental perfusion and improve the supply of nutrients and oxygen to the fetus in the short-term; however, this pathway is detrimental in the long run. When this path does not work sufficiently, stillbirths may occur. Therefore, stillbirths are generally related to the development of preeclampsia. However, we found lower stillbirth rates with preeclampsia pregnancies. This association may be due to the fact that women with preeclampsia may be exposed to improved or optimised prenatal care and may be monitored better during pregnancy after diagnosis. We believe that this observation proves that preeclampsia screening is beneficial. The reported OR should therefore be interpreted carefully. We conclude that higher maternal age, several social risks, obesity and gestational diabetes are strongly related to preeclampsia. Further studies and interventions regarding prenatal care should therefore not only focus on how better diagnostic and treatment procedures can be implemented but also on how these diagnostic and treatment procedures reach obese and/or older women of low socio-economic status. Perinatal and maternal morbidity may not decrease any further if we are not able to clearly target these high-risk groups of women. Otherwise, prenatal care will only become more expensive and thus even more ineffective. Increasing maternal age as well as increasing rates of maternal obesity justifies this change of focus. We are the first scientific research team that was granted access to this sensitive data. To our knowledge, our study of these specific topics is the most comprehensive to date.

Acknowledgements
This publication was based on a research visit of the first (Sv.S.) and last (B.H.) authors to the Bundesgescha ftsstelle Qualita tssicherung gGmbH (BQS, Du sseldorf, Germany). We would like to thank Mrs. Sandu, BQS staff scientist, for assessing and preparing the data, for valuable technical and method information and for discussing and interpreting the results. Finally, we wish to thank Dr. Shelby Yamamoto, PhD, Tatiana Yarmoliuk, M.A. and Christina Huy, Dipl.-Inform. Med. (all MIPH) for their assistance in preparing this manuscript.

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ducted in developed countries between 1997 and 2006. Eur J Contracept Reprod Health Care. 2008;13:13847. Schneider S, Huy C, Schutz J, Diehl K. Smoking cessation during pregnancy: a systematic literature review. Drug Alcohol Rev. 2010;29:8190. Sebire NJ, Jolly M, Harris J, Regan L, Robinson S. Is maternal underweight really a risk factor for adverse pregnancy outcome? A population-based study in London. Br J Obstet Gynaecol. 2001;108:616. Sebire NJ, Jolly M, Harris JP, Wadsworth J, Joffe M, Beard RW, et al. Maternal obesity and pregnancy outcome: a study of 287,213 pregnancies in London. Int J Obes Relat Metab Disord 2001;25:117582. Sibai BM, Ewell M, Levine RJ, Klebanoff MA, Esterlitz J, Catalano PM, et al. Risk factors associated with preeclampsia in healthy nulliparous women. The Calcium for Preeclampsia Prevention (CPEP) Study Group. Am J Obstet Gynecol. 1997; 177:100310. Simoes E, Kunz S, Bosing-Schwenkglenks M, Schwoerer P, Schmahl FW. Inanspruchnahme der Schwangerenvorsorge-ein Spiegel gesellschaftlicher Entwicklungen und Aspekte der Effizienz. Untersuchung auf Basis der Perinatalerhebung Baden-Wu rttemberg 1998-2001 w Utilization and Effectiveness of Prenatal Care-A Mirror of Social Development. Study Based on Perinatal Survey Data in Baden-Wu rttembergx (in German). Geburtsh Frauenheilk. 2003;63:53845. Sun Y, Yang H, Sun WJ. Risk factors for pre-eclampsia in pregnant Chinese women with abnormal glucose metabolism. Int J Gynaecol Obstet. 2008;101:746. Vatten LJ, Skjaerven R. Is pre-eclampsia more than one disease? Br J Obstet Gynaecol. 2004;111:298302. Verlohren S, Galindo A, Schlembach D, Zeisler H, Herraiz I, Moertl MG, et al. An automated method for the determination of the sFlt-1/PIGF ratio in the assessment of preeclampsia. Am J Obstet Gynecol. 2009. Wendland EM, Duncan BB, Belizan JM, Vigo A, Schmidt MI. Gestational diabetes and pre-eclampsia: common antecedents? Arq Bras Endocrinol Metab. 2008;52:97584.

The authors stated that there are no conflicts of interest regarding the publication of this article. Received May 7, 2010. Revised October 7, 2004. Accepted October 21, 2010. Previously published online March 10, 2011.

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264 Schneider et al., Risk groups and outcomes of preeclampsia

Attachment: Risk groups and neonatal outcomes of preeclampsia Current result from the national German Perinatal Quality Registry w 8x
German Federal Agency for Quality Assurance. Qualita tsreport 2006 w Quality Report 2006x (in German). Du sseldorf: Bundesgescha ftsstelle Qualita tssicherung; 2007. Variables in data set Obstetrics 1. Data set Mother Basic Documentation Mother 1. ID number of mother 2. Date of birth of pregnant women 3. Date of admittance 4.1 Admittance diagnosis 5.1 Number of days of treatment before admission in hospital 5.2 Number of days of treatment after discharge from hospital 6. Postcode of city of residence 7.1 Nationality: Germany (yes/no) 7.2 Nationality: Other country 1. Central and Northern Europe, North America 2. Mediterranean countries 3. Eastern Europe 4. Asia 5. Other countries 8. Single mother (yes/no) 9.1 Occupation before/during current pregnancy 9.2 Kind of occupation 1. Housewife 2. Student/Trainee 3. Unskilled worker 4. Skilled worker, middle service 5. Higher service, higher executive, self-employed, freelancer 6. Other 10.1 Amount of preceded pregnancies Current pregnancy 11. Number of cigarettes (per day) after confirming pregnancy 12. Appointment at doctors/maternity clinic during the pregnancy (yes/no) 13. Pregnancy registered as a high-risk pregnancy in the maternity log 14.1 Pregnancy risks (yes/no) 14.2 Pregnancy risk 1. Psycho-social stress 2. Familiar stress 3. Diabetes mellitus 4. Obesity 5. Long-term medication 6. Substance abuse 7. Placenta praevia 8. Placental insufficiency 9. Anemia 10. Hypertension (blood pressure 140/90) 11. Proteinuria 12. Edema 13. Gestational diabetes 14. HELLP syndrome 15. Eclampsia 16. Others 15. Total number of inpatient stays in clinic during pregnancy (in days) 16.1 Week of pregnancy when the first stay in clinic registered 17.1 Week of pregnancy when the first examination conducted 17.2 Total number of prenatal care/prenatal examinations 18.1 Week of pregnancy when the first ultrasound examination was conducted 18.2 Total number of ultrasound examinations 19. Body weight at the first examination 20. Last body weight before delivery 21. Body height 22. Chorionic villus biopsy (yes/no) 23. Aminocentesis (until 22 weeks) 24. Contraction stress test 25. Doppler ultrasonography (yes/no) 26. Pessary placed (yes/no) 27. Tocolysis 28. Expected adjusted date of delivery 29. Antenatal diagnosed/suspected malformations Information about delivery 30. Kind of admittance 31. Uterine orifice 32. Lung maturity treatment 33. Last lung maturity treatment on: (date) 34. Admittance CTG 35.1 Doppler ultrasonography conducted in obstetric unit 36.1 Delivery risks (yes/no) 36.2 Delivery risk: 1. Premature rupture of membranes 2. Exceeding of delivery date 3. Malformation 4. Placental insufficiency 5. Eclampsia 6. Diabetes mellitus 7. Uterine bleedings

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Schneider et al., Risk groups and outcomes of preeclampsia 265

8. Diseases of mother 9. Complications of umbilical cord 10. Abnormal position of fetus 11. HELLP syndrome 12. Intrauterine death of fetus 13. Shoulder dystocia 14. Others 37.-41. See below 42. Medicamentous cervix maturation (yes/no) 43. Induced delivery (yes/no) 43.1 Indication for 43 44. Oxytocics 45. Tocolysis 46. Analgetics 47. Acupuncture Complications Mother 48.-73. See below 74. Perineal laceration 75. Other lacerations 76. Bleeding )1000 mL 77. Wound healing/need of treatment 78. Hysterectomy/Laparotomy 79. Eclampsia 80. Sepsis 81. Fever during puerperal )388C )2 days 82. Anemia Hb -10 g/dL (- 6.2 mmol/L) 83.1 General complications in need of treatment 1. Pneumonia 2. Cardiovascular disease 3. Deep vein thrombosis 4. Lung embolism 5. Infection of the urinary tract 6. Others 84.-90. See below 91.1 Discharge diagnosis 92. Discharge reason mother 93. Discharge date mother 94. Death of mother (yes/no) 2. Data Set Newborn 1. ID number of newborn 33.1 Rupture of membranes before onset of labor 37.1 CTG-Control 38.1 Blood gas analysis fetal blood 39. Position 40. Delivery position at the time of birth 41.1 Duration of labor 45.1 Anesthesia 51.1 Indication for operative delivery 1. Premature rupture of membranes 2. Exceeding of delivery date 3. Malformation 4. Placental insufficiency 5. Eclampsia 6. Diabetes mellitus

7. Pathologic CTG 8. Protracted delivery or delivery stagnation 9. Absolute or relative disproportion of fetal head and mothers pelvis 10. Complications of umbilical cord 11. Abnormal position of fetus 12. HELLP syndrome 13. Intrauterine death of fetus 14. Shoulder dystocia 15. Others 51.2 Duration of intervention during caesarean section 53.1 Emergency caesarean section 53.2 Indication for 53.1: 1. Premature rupture of membranes 2. Exceeding of delivery date 3. Malformation 4. Placental insufficiency 5. Eclampsia 6. Diabetes mellitus 7. Pathologic CTG or bad fetal heart tones 8. Protracted delivery or delivery stagnation 9. Absolute or relative disproportion of fetal head and mothers pelvis 10. Complications of umbilical cord 11. Abnormal position of fetus 12. HELLP syndrome 13. Intrauterine death of fetus 14. Shoulder dystocia 15. Others Basic documentation Newborn 60.1 Date of birth 60.2 Time of birth 61.1 Birth diagnosis 62. Sex of the child 63. Apgar score (1 min., 5 min., 10 min. after birth) 64. Weight 65.1 Length 65.2 Head circumference 66.1 Blood gas analysis 67. Pulse oximetry 68. Intubation 70. Malformation 71. Prenatally diagnosed malformation 72. Diagnosed morbidity of the newborn 73. Stillbirth 74.-83. See above 84.1 Newborn moved into childrens hospital 85.1 Discharge date from the maternity clinic 86. Final discharge from/death in (maternity/childrens hospital) 87. Discharge diagnosis 88. Discharge reason 89. Death of the born-alive infant within first 7 days 90.1 Cause of death born-alive infant 90.2 Date of death born-alive infant 90.3 Time of death born-alive infant

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