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Introduction: There is important clinical information from placental weight and its ratio to the fetal weight. The aim with this study was to establish reference values for the placental weight and the placental:fetal weight ratio for gestational weeks 13-43 in a Swedish population., Materials and Methods: Cases were retrospectively collected from the database used at the Pathology Department at Karolinska University Hospital and information about the placental weight, fetal weight, and gestational age was retrieved. Conditions, which could affect the placental- or fetal weight were excluded. Thereafter percentile curves were calculated for the placental weight and the placental:fetal weight ratio for gestational weeks., Results: A total of 730 cases were included and percentile curves for the placental weight for gestational week 13-43 and placental:fetal weight ratio for gestational week 18-43 are presented., Conclusions: Reference values for post fixation placental weight and its ratio to fetal weight for a Swedish population are presented. The reference values are lower than the current reference values used in our institution, and this will be of importance when interpreting findings after placental examination., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To investigate the risk of stillbirth in relation to (1) a previous caesarean delivery (CD) compared with those following a vaginal birth (VB); and (2) vaginal birth after caesarean (VBAC) compared with a repeat CD., Design: Population-based cohort study., Setting: The Swedish Medical Birth registry., Population: Women with their first and second singletons between 1982 and 2012., Methods: Multivariable logistic regression models were performed to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) of the association between CD in the first pregnancy and stillbirth in the second pregnancy and the association between VBAC and stillbirth. Sub-group analyses were performed by types of CD and timing of stillbirth (antepartum and intrapartum)., Main Outcome Measures: Stillbirth (antepartum and intrapartum fetal death)., Results: Of the 1 771 700 singleton births from 885 850 women, 117 114 (13.2%) women had a CD in the first pregnancy, and 51 755 had VBAC in the second pregnancy. We found a 37% increased odds of stillbirth (aOR 1.37; 95% CI 1.23-1.52) in women with a previous CD compared with VB. The odds of intrapartum stillbirth were higher in the previous pre-labour CD group (aOR 2.72; 95% CI 1.51-4.91) and in the previous in-labour CD group (aOR 1.35; 95% CI 0.76-2.40), although not statistically significant in the latter case. No increased odds were found for intrapartum stillbirth in women who had VBAC (aOR 0.99; 95% CI 0.48-2.06) compared with women who had a repeat CD., Conclusions: This study confirms that a CD is associated with an increased risk of subsequent stillbirth, with a greater risk among pre-labour CD. This association is not solely mediated by increases in intrapartum asphyxia, uterine rupture or attempted VBAC. Further research is needed to understand this association, but these findings might help healthcare providers to reach optimal decisions regarding mode of birth, particularly when CD is unnecessary., (© 2024 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: Improved Pregnancy Outcomes via Early Detection (IMPROvED) is a multi-centre, European phase IIa clinical study. The primary aim of IMPROvED is to enable the assessment and refinement of innovative prototype preeclampsia risk assessment tests based on emerging biomarker technologies. Here we describe IMPROvED's profile and invite researchers to collaborate., Methods: A total of 4,038 low-risk nulliparous singleton pregnancies were recruited from maternity units in Ireland (N=1,501), United Kingdom (N=1,108), The Netherlands (N=810), and Sweden (N=619) between November 2013 to August 2017. Participants were interviewed by a research midwife at ~11 weeks (optional visit), ~15 weeks, ~20 weeks, ~34 weeks' gestation (optional visit), and postpartum (within 72-hours following delivery)., Findings to Date: Clinical data included information on maternal sociodemographic, medical history, and lifestyle factors collected at ~15 weeks' gestation, and maternal measurements, collected at each study visit. Biobank samples included blood, urine, and hair collected at each study visit throughout pregnancy in all units plus umbilical cord/blood samples collected at birth in Ireland and Sweden. A total of 74.0% (N=2,922) had an uncomplicated pregnancy, 3.1% (N=122) developed preeclampsia, 3.6% (N=143) had a spontaneous preterm birth, and 10.5% (N=416) had a small for gestational age baby. We evaluated a panel of metabolite biomarkers and a panel of protein biomarkers at 15 weeks and 20 weeks' gestation for preeclampsia risk assessment. Their translation into tests with clinical application, as conducted by commercial entities, was hampered by technical issues and changes in test requirements. Work on the panel of proteins was abandoned, while work on the use of metabolite biomarkers for preeclampsia risk assessment is ongoing., Future Plans: In accordance with the original goals of the IMPROvED study, the data and biobank are now available for international collaboration to conduct high quality research into the cause and prevention of adverse pregnancy outcomes., Competing Interests: Competing interests: RT is an employee of Metabolomic Diagnostics. RT is a named inventor on several patent applications regarding the use of biomarkers to predict preeclampsia risk; the associated rights are assigned to Metabolomic Diagnostics. PNB and LCK are minority shareholders in Metabolomic Diagnostics, which seeks to develop predictive tests for major pregnancy complications. All other authors have no conflicts of interest to disclose, including financial interest., (Copyright: © 2024 Maher GM et al.)

Introduction: Our study evaluated how a history of stillbirth in either of the first two pregnancies affects the risk of having a stillbirth or other adverse pregnancy outcomes in the third subsequent pregnancy., Material and Methods: We used the Swedish Medical Birth Register to define a population-based cohort of women who had at least three singleton births from 1973 to 2012. The exposure of interest was a history of stillbirth in either of the first two pregnancies. The primary outcome was subsequent stillbirth in the third pregnancy. Secondary outcomes included: preterm birth, preeclampsia, placental abruption and small-for-gestational-age infant. Adjusted logistic regression was performed including maternal age, body mass index, smoking, diabetes and hypertension. A sensitivity analysis was performed excluding stillbirths associated with congenital anomalies, pregestational and gestational diabetes, hypertension and preterm stillbirths., Results: The study contained data on 1 316 175 births, including 8911 stillbirths. Compared with women who had two live births, the highest odds of stillbirth in the third pregnancy were observed in women who had two stillbirths (adjusted odds ratio [aOR] 11.40, 95% confidence interval [95% CI] 2.75-47.70), followed by those who had stillbirth in the second birth (live birth-stillbirth) (aOR 3.59, 95% CI 2.58-4.98), but the odds were still elevated in those whose first birth ended in stillbirth (stillbirth-live birth) (aOR 2.35, 1.68, 3.28). Preterm birth, pre-eclampsia and placental abruption followed a similar pattern. The odds of having a small-for-gestational-age infant were highest in women whose first birth ended in stillbirth (aOR 1.93, 95% CI 1.66-2.24). The increased odds of having a stillbirth in a third pregnancy when either of the earlier births ended in stillbirth remained when stillbirths associated with congenital anomalies, pregestational and gestational diabetes, hypertension or preterm stillbirths were excluded. However, when preterm stillbirths were excluded, the strength of the association was reduced., Conclusions: Even when they have had a live-born infant, women with a history of stillbirth have an increased risk of adverse pregnancy outcomes; this cannot be solely accounted for by the recurrence of congenital anomalies or maternal medical disorders. This suggests that women with a history of stillbirth should be offered additional surveillance for subsequent pregnancies., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Introduction: Previous evidence examining the association between socioeconomic status and pregnancy complications are conflicted and often limited to using area-based measures of socioeconomic status. In this study, we aimed to examine the association between individual-level socioeconomic factors and a wide range of adverse pregnancy and neonatal outcomes using data from the IMPROvED birth cohort conducted in Sweden, the Netherlands and Republic of Ireland., Material and Methods: The study cohort consisted of women who participated in the IMPROvED birth cohort between 2013 and 2017. Data on socioeconomic factors were self-reported and obtained at 15 weeks' gestation, and included level of education, employment status, relationship status, and income. Data on pregnancy and neonatal outcomes included gestational hypertension, pre-eclampsia, gestational diabetes mellitus, emergency cesarean section, preterm birth, post term delivery, small for gestational age and Apgar score at 1 min. These data were obtained within 72 h following delivery and confirmed using medical records. Multivariable logistic regression examined the association between each socioeconomic variable and each outcome separately adjusting for maternal age, maternal body mass index, maternal smoking, maternal alcohol consumption and cohort center. We also examined the effect of exposure to any ≥2 risk factors compared to none., Results: A total of 2879 participants were included. Adjusted results suggested that those with less than third level of education had an increased odds of gestational hypertension (OR: 1.74, 95% CI: 1.23-2.46), while those on a middle level of income had a reduced odds of emergency cesarean section (OR: 0.59, 95% CI: 0.42-0.84). No significant associations were observed between socioeconomic variables and neonatal outcomes. Exposure to any ≥2 socioeconomic risk factors was associated with an increased risk of preterm birth (OR: 1.75, 95% CI: 1.06-2.89)., Conclusions: We did not find strong evidence of associations between individual-level socioeconomic factors and pregnancy and neonatal outcomes in high-income settings overall, with only few significant associations observed among pregnancy outcomes., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Introduction: Risk evaluation for preeclampsia in early pregnancy allows identification of women at high risk. Prediction models for preeclampsia often include circulating concentrations of placental growth factor (PlGF); however, the models are usually limited to a specific PlGF method of analysis. The aim of this study was to compare three different PlGF methods of analysis in a Swedish cohort to assess their convergent validity and appropriateness for use in preeclampsia risk prediction models in the first trimester of pregnancy., Material and Methods: First-trimester blood samples were collected in gestational week 11 +0 to 13 +6 from 150 pregnant women at Uppsala University Hospital during November 2018 until November 2020. These samples were analyzed using the different PlGF methods from Perkin Elmer, Roche Diagnostics, and Thermo Fisher Scientific., Results: There were strong correlations between the PlGF results obtained with the three methods, but the slopes of the correlations clearly differed from 1.0: PlGF PerkinElmer  = 0.553 (95% confidence interval [CI] 0.518-0.588) * PlGF Roche -1.112 (95% CI -2.773 to 0.550); r = 0.966, mean difference -24.6 (95% CI -26.4 to -22.8). PlGF PerkinElmer  = 0.673 (95% CI 0.618-0.729) * PlGF ThermoFisher -0.199 (95% CI -2.292 to 1.894); r = 0.945, mean difference -13.8 (95% CI -15.1 to -12.6). PlGF Roche  = 1.809 (95% CI 1.694-1.923) * PlGF PerkinElmer +2.010 (95% CI -0.877 to 4.897); r = 0.966, mean difference 24.6 (95% CI 22.8-26.4). PlGF Roche  = 1.237 (95% CI 1.113-1.361) * PlGF ThermoFisher +0.840 (95% CI -3.684 to 5.363); r = 0.937, mean difference 10.8 (95% CI 9.4-12.1). PlGF ThermoFisher  = 1.485 (95% CI 1.363-1.607) * PlGF PerkinElmer +0.296 (95% CI -2.784 to 3.375); r = 0.945, mean difference 13.8 (95% CI 12.6-15.1). PlGF ThermoFisher  = 0.808 (95% CI 0.726-0.891) * PlGF Roche -0.679 (95% CI -4.456 to 3.099); r = 0.937, mean difference -10.8 (95% CI -12.1 to -9.4)., Conclusion: The three PlGF methods have different calibrations. This is most likely due to the lack of an internationally accepted reference material for PlGF. Despite different calibrations, the Deming regression analysis indicated good agreement between the three methods, which suggests that results from one method may be converted to the others and hence used in first-trimester prediction models for preeclampsia., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Gestational diabetes (GDM) is associated with increased risk of type 2 diabetes (T2DM) and cardiovascular disease. It is uncertain whether GDM is independently associated with the risk of chronic kidney disease. The aim was to examine the association between GDM and maternal CKD and end-stage kidney disease (ESKD) and to determine whether this depends on progression to overt T2DM., Methods: A population-based cohort study was designed using Swedish national registry data. Previous GDM diagnosis was the main exposure, and this was stratified according to whether women developed T2DM after pregnancy. Using Cox regression models, we estimated the risk of CKD (stages 3-5), ESKD and different CKD subtypes (tubulointerstitial, glomerular, hypertensive, diabetic, other)., Findings: There were 1,121,633 women included, of whom 15,595 (1·4%) were diagnosed with GDM. Overall, GDM-diagnosed women were at increased risk of CKD (aHR 1·81, 95% CI 1·54-2·14) and ESKD (aHR 4·52, 95% CI 2·75-7·44). Associations were strongest for diabetic CKD (aHR 8·81, 95% CI 6·36-12·19) and hypertensive CKD (aHR 2·46, 95% CI 1·06-5·69). These associations were largely explained by post-pregnancy T2DM. Among women who had GDM + subsequent T2DM, strong associations were observed (CKD, aHR 21·70, 95% CI 17·17-27·42; ESKD, aHR 112·37, 95% CI 61·22-206·38). But among those with GDM only, associations were non-significant (CKD, aHR 1·11, 95% CI 0·89-1·38; ESKD, aHR 1·58, 95% CI 0·70-3·60 respectively)., Conclusion: Women who experience GDM and subsequent T2DM are at increased risk of developing CKD and ESKD. However, GDM-diagnosed women who never develop overt T2DM have similar risk of future CKD/ESKD to those with uncomplicated pregnancies., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: ME has participated in advisory board meetings (Astellas, Astra Zeneca, Vifor Pharma) and has received payment for lectures (Astellas, Vifor Pharma). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Maternal chronic kidney disease and chronic hypertension have been linked with adverse pregnancy outcomes. We aimed to examine the association between these conditions and adverse pregnancy outcomes over the last 3 decades., Objective: We conducted this national cohort study to assess the association between maternal chronic disease (CH, CKD or both conditions) and adverse pregnancy outcomes with an emphasis on the effect of parity, maternal age, and BMI on these associations over the last three decades. We further investigated whether different subtypes of CKD had differing effects., Study Design: We used data from the Swedish Medical Birth Register, including 2,788,490 singleton births between 1982 and 2012. Women with chronic kidney disease and chronic hypertension were identified from the Medical Birth Register and National Patient Register. Logistic regression models were performed to assess the associations between maternal chronic disease (chronic hypertension, chronic kidney disease, or both conditions) and pregnancy outcomes, including preeclampsia, in-labor and prelabor cesarean delivery, preterm birth, small for gestational age, and stillbirth., Results: During the 30-year study period, 22,397 babies (0.8%) were born to women with chronic kidney disease, 13,279 (0.48%) to women with chronic hypertension and 1079 (0.04%) to women with both conditions. Associations with chronic hypertension were strongest for preeclampsia (adjusted odds ratio, 4.57; 95% confidence interval, 4.33-4.84) and stillbirth (adjusted odds ratio, 1.65; 95% confidence interval, 1.35-2.03) and weakest for spontaneous preterm birth (adjusted odds ratio, 1.07; 95% confidence interval, 0.96-1.20). The effect of chronic kidney disease varied from (adjusted odds ratio, 2.05; 95% confidence interval, 1.92-2.19) for indicated preterm birth to no effect for stillbirth (adjusted odds ratio, 1.16; 95% confidence interval, 0.95-1.43). Women with both conditions had the strongest associations for in-labor cesarean delivery (adjusted odds ratio, 1.86; 95% confidence interval, 1.49-2.32), prelabor cesarean delivery (adjusted odds ratio, 2.68; 95% confidence interval, 2.18-3.28), indicated preterm birth (adjusted odds ratio, 9.09; 95% confidence interval, 7.61-10.7), and small for gestational age (adjusted odds ratio, 4.52; 95% confidence interval, 3.68-5.57). The results remained constant over the last 3 decades. Stratified analyses of the associations by parity, maternal age, and body mass index showed that adverse outcomes remained independently higher in women with these conditions, with worse outcomes in multiparous women. All chronic kidney disease subtypes were associated with higher odds of preeclampsia, in-labor cesarean delivery, and medically indicated preterm birth. Different subtypes of chronic kidney disease had differing risks; strongest associations of preeclampsia (adjusted odds ratio, 3.98; 95% confidence interval, 2.98-5.31) and stillbirth (adjusted odds ratio, 2.73; 95% confidence interval, 1.13-6.59) were observed in women with congenital kidney disease, whereas women with diabetic nephropathy had the most pronounced increase odds of in-labor cesarean delivery (adjusted odds ratio, 3.54; 95% confidence interval, 2.06-6.09), prelabor cesarean delivery (adjusted odds ratio, 7.50; 95% confidence interval, 4.74-11.9), and small for gestational age (adjusted odds ratio, 4.50; 95% confidence interval, 2.92-6.94). In addition, women with renovascular disease had the highest increased risk of preterm birth in both spontaneous preterm birth (adjusted odds ratio, 3.01; 95% confidence interval, 1.57-5.76) and indicated preterm birth (adjusted odds ratio, 8.09; 95% confidence interval, 5.73-11.4)., Conclusion: Women with chronic hypertension, chronic kidney disease, or both conditions are at an increased risk of adverse pregnancy outcomes which were independent of maternal age, body mass index, and parity. Multidisciplinary management should be provided with intensive clinical follow-up to support these women during pregnancy, particularly multiparous women. Further research is needed to evaluate the effect of disease severity on adverse pregnancy outcomes., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: First-trimester pregnancy risk evaluation facilitates individualised antenatal care, as well as application of preventive strategies for pre-eclampsia or birth of a small for gestational age infant. A range of early intervention strategies in pregnancies identified as high risk at the end of the first trimester has been shown to decrease the risk of preterm pre-eclampsia (<37 gestational weeks). The aim of this project is to create the Improving Maternal Pregnancy And Child ouTcomes (IMPACT) database; a nationwide database with individual patient data, including predictors recorded at the end of the first trimester and later pregnancy outcomes, to identify women at high risk of pre-eclampsia. A second aim is to link the IMPACT database to a biobank with first-trimester blood samples., Methods and Analysis: This is a Swedish prospective multicentre cohort study. Women are included between the 11th and 14th weeks of pregnancy. At inclusion, pre-identified predictors are retrieved by interviews and medical examinations. Blood samples are collected and stored in a biobank. Additional predictors and pregnancy outcomes are retrieved from the Swedish Pregnancy Register. Inclusion in the study began in November 2018 with a targeted sample size of 45 000 pregnancies by end of 2021. Creation of a new risk prediction model will then be developed, validated and implemented. The database and biobank will enable future research on prediction of various pregnancy-related complications., Ethics and Dissemination: Confidentiality aspects such as data encryption and storage comply with the General Data Protection Regulation and with ethical committee requirements. This study has been granted national ethical approval by the Swedish Ethical Review Authority (Uppsala 2018-231) and national biobank approval at Uppsala Biobank (18237 2 2018 231). Results from the current as well as future studies using information from the IMPACT database will be published in peer-reviewed journals., Trial Registration Number: NCT03831490., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Stillbirth is a devastating adverse pregnancy outcome that may occur without any obvious reason or may occur in the context of fetal growth restriction, preeclampsia, or other obstetric complications. There is increasing evidence that women who experience stillbirths are at greater risk of long-term cardiovascular disease, but little is known about their risk of chronic kidney disease and end-stage renal disease. We conducted the largest study to date to investigate the subsequent risk of maternal chronic kidney disease and end-stage renal disease following stillbirth., Objective: To identify whether pregnancy complicated by stillbirth is associated with subsequent risk of maternal chronic kidney disease and end-stage renal disease, independent of underlying medical or obstetric comorbidities., Study Design/methods: We conducted a population-based cohort study using nationwide data from the Swedish Medical Birth Register, National Patient Register, and Swedish Renal Register. We included all women who had live births and stillbirths from 1973 to 2012, with follow-up to 2013. Women with preexisting renal disease were excluded. Cox proportional hazard regression models were used to estimate adjusted hazard ratios and 95% confidence intervals for associations between stillbirth and maternal chronic kidney disease and end-stage renal disease respectively. We controlled for maternal age, year of delivery, country of origin, parity, body mass index, smoking, gestational diabetes, preeclampsia, and small for gestational age deliveries. Women who had a history of medical comorbidities, which may predispose to renal disease (prepregnancy cardiovascular disease, hypertension, diabetes, lupus, systemic sclerosis, hemoglobinopathy, or coagulopathy), were excluded from the main analysis and examined separately., Results: There were 1,941,057 unique women who had 3,755,444 singleton pregnancies, followed up over 42,313,758 person-years. The median follow-up time was 20.7 years (interquartile range, 9.9-30.0 years). 13,032 women (0.7%) had at least 1 stillbirth. Women who had experienced at least 1 stillbirth had a greater risk of developing chronic kidney disease (adjusted hazard ratio, 1.26; 95% confidence interval, 1.09-1.45) and end-stage renal disease (adjusted hazard ratio, 2.25; 95% confidence interval, 1.55-3.25) compared with women who only had live births. These associations persisted after removing all stillbirths that occurred in the context of preeclampsia, and small for gestational age or congenital malformations (for chronic kidney disease, adjusted hazard ratio, 1.33; 95% confidence interval, 1.13-1.57; for end-stage renal disease, adjusted hazard ratio, 2.95; 95% confidence interval, CI 1.86-4.68). There was no significant association observed between stillbirth and either chronic kidney disease or end-stage renal disease in women who had preexisting medical comorbidities (chronic kidney disease, adjusted hazard ratio, 1.13; 95% confidence interval, 0.73-1.75 or end-stage renal disease, adjusted hazard ratio, 1.49; 95% confidence interval, 0.78-2.85)., Conclusion: Women who have a history of stillbirth may be at increased risk of chronic kidney disease and end-stage renal disease compared with women who have only had live births. This association persists independently of preeclampsia, and small for gestational age, maternal smoking, obesity, and medical comorbidities. Further research is required to determine whether affected women would benefit from closer surveillance and follow-up for future renal disease., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Hypertensive disorders of pregnancy (HDP) (preeclampsia, gestational hypertension) are associated with an increased risk of end-stage kidney disease (ESKD). Evidence for associations between HDP and chronic kidney disease (CKD) is more limited and inconsistent. The underlying causes of CKD are wide-ranging, and HDP may have differential associations with various aetiologies of CKD. We aimed to measure associations between HDP and maternal CKD in women who have had at least one live birth and to identify whether the risk differs by CKD aetiology., Methods and Findings: Using data from the Swedish Medical Birth Register (MBR), singleton live births from 1973 to 2012 were identified and linked to data from the Swedish Renal Register (SRR) and National Patient Register (NPR; up to 2013). Preeclampsia was the main exposure of interest and was treated as a time-dependent variable. Gestational hypertension was also investigated as a secondary exposure. The primary outcome was maternal CKD, and this was classified into 5 subtypes: hypertensive, diabetic, glomerular/proteinuric, tubulointerstitial, and other/nonspecific CKD. Cox proportional hazard regression models were used, adjusting for maternal age, country of origin, education level, antenatal BMI, smoking during pregnancy, gestational diabetes, and parity. Women with pre-pregnancy comorbidities were excluded. The final sample consisted of 1,924,409 women who had 3,726,554 singleton live births. The mean (±SD) age of women at first delivery was 27.0 (±5.1) years. Median follow-up was 20.7 (interquartile range [IQR] 9.9-30.0) years. A total of 90,917 women (4.7%) were diagnosed with preeclampsia, 43,964 (2.3%) had gestational hypertension, and 18,477 (0.9%) developed CKD. Preeclampsia was associated with a higher risk of developing CKD during follow-up (adjusted hazard ratio [aHR] 1.92, 95% CI 1.83-2.03, p < 0.001). This risk differed by CKD subtype and was higher for hypertensive CKD (aHR 3.72, 95% CI 3.05-4.53, p < 0.001), diabetic CKD (aHR 3.94, 95% CI 3.38-4.60, p < 0.001), and glomerular/proteinuric CKD (aHR 2.06, 95% CI 1.88-2.26, p < 0.001). More modest associations were observed between preeclampsia and tubulointerstitial CKD (aHR 1.44, 95% CI 1.24-1.68, p < 0.001) or other/nonspecific CKD (aHR 1.51, 95% CI 1.38-1.65, p < 0.001). The risk of CKD was increased after preterm preeclampsia, recurrent preeclampsia, or preeclampsia complicated by pre-pregnancy obesity. Women who had gestational hypertension also had increased risk of developing CKD (aHR 1.49, 95% CI 1.38-1.61, p < 0.001). This association was strongest for hypertensive CKD (aHR 3.13, 95% CI 2.47-3.97, p < 0.001). Limitations of the study are the possibility that cases of CKD were underdiagnosed in the national registers, and some women may have been too young to have developed symptomatic CKD despite the long follow-up time. Underreporting of postpartum hypertension is also possible., Conclusions: In this study, we found that HDP are associated with increased risk of maternal CKD, particularly hypertensive or diabetic forms of CKD. The risk is higher after preterm preeclampsia, recurrent preeclampsia, or preeclampsia complicated by pre-pregnancy obesity. Women who experience HDP may benefit from future systematic renal monitoring., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: ME has participated in advisory board meetings (Astellas, Astra Zeneca, Vifor Pharma) and has received payment for lectures (Astellas, Vifor Pharma).

Background: Preterm delivery is an independent risk factor for maternal cardiovascular disease. Little is known about the association between preterm delivery and maternal renal function. This study aimed to examine whether women who experience preterm delivery are at increased risk of subsequent chronic kidney disease (CKD) and end-stage kidney disease (ESKD)., Methods: Using data from the Swedish Medical Birth Register, singleton live births from 1973 to 2012 were identified and linked to data from the Swedish Renal Register and National Patient Register (up to 2013). Gestational age at delivery was the main exposure and treated as a time-dependent variable. Primary outcomes were maternal CKD or ESKD. Cox proportional hazard regression models were used for analysis., Results: The dataset included 1,943,716 women who had 3,760,429 singleton live births. The median follow-up was 20.6 (interquartile range 9.9-30.0) years. Overall, 162,918 women (8.4%) delivered at least 1 preterm infant (< 37 weeks). Women who had any preterm delivery (< 37 weeks) were at increased risk of CKD (adjusted hazard ratio (aHR) 1.39, 95% CI 1.32-1.45) and ESKD (aHR 2.22, 95% CI 1.90-2.58) compared with women who only delivered at term (≥ 37 weeks). Women who delivered an extremely preterm infant (< 28 weeks) were at increased risk of CKD (aHR 1.84, 95% CI 1.52-2.22) and ESKD (aHR 3.61, 95% CI 2.03-6.39). The highest risk of CKD and ESKD was in women who experienced preterm delivery + preeclampsia (vs. non-preeclamptic term deliveries, for CKD, aHR 2.81, 95% CI 2.46-3.20; for ESKD, aHR 6.70, 95% CI 4.70-9.56). However, spontaneous preterm delivery was also associated with increased risk of CKD (aHR 1.32, 95% CI 1.25-1.39) and ESKD (aHR 1.99, 95% CI 1.67-2.38) independent of preeclampsia or small for gestational age (SGA)., Conclusions: Women with history of preterm delivery are at increased risk of CKD and ESKD. The risk is higher among women who had very preterm or extremely preterm deliveries, or whose preterm delivery was medically indicated. Women who experience spontaneous preterm delivery are at increased risk of long-term renal disease independent of preeclampsia or SGA. Preterm delivery may act as a risk marker for adverse maternal renal outcomes.

Importance: Adverse pregnancy outcomes, such as hypertensive disorders of pregnancy, gestational diabetes, and preterm delivery, are associated with increased risk of maternal cardiovascular disease. Little is known about whether adverse pregnancy outcomes are associated with increased risk of maternal chronic kidney disease (CKD) and end-stage kidney disease (ESKD)., Objective: To review and synthesize the published literature on adverse pregnancy outcomes (hypertensive disorders of pregnancy, gestational diabetes, and preterm delivery) and subsequent maternal CKD and ESKD., Data Sources: PubMed, Embase, and Web of Science were searched from inception to July 31, 2019, for cohort and case-control studies of adverse pregnancy outcomes and maternal CKD and ESKD., Study Selection: Selected studies included the following: a population of pregnant women, exposure to an adverse pregnancy outcome of interest, and at least 1 primary outcome (CKD or ESKD) or secondary outcome (hospitalization or death due to kidney disease). Adverse pregnancy outcomes included exposure to hypertensive disorders of pregnancy (preeclampsia, gestational hypertension, or chronic hypertension), preterm delivery (<37 weeks), and gestational diabetes. Three reviewers were involved in study selection. Of 5656 studies retrieved, 23 were eligible for inclusion., Data Extraction and Synthesis: The Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines were followed throughout. Three reviewers extracted data and appraised study quality. Random-effects meta-analyses were used to calculate overall pooled estimates using the generic inverse variance method., Main Outcomes and Measures: Primary outcomes included CKD and ESKD diagnosis, defined using established clinical criteria (estimated glomerular filtration rate or albuminuria values) or hospital records. The protocol for this systematic review was registered on PROSPERO (CRD42018110891)., Results: Of 23 studies included (5 769 891 participants), 5 studies reported effect estimates for more than 1 adverse pregnancy outcome. Preeclampsia was associated with significantly increased risk of CKD (pooled adjusted risk ratio [aRR], 2.11; 95% CI, 1.72-2.59), ESKD (aRR, 4.90; 95% CI, 3.56-6.74), and kidney-related hospitalization (aRR, 2.65; 95% CI, 1.03-6.77). Gestational hypertension was associated with increased risk of CKD (aRR, 1.49; 95% CI, 1.11-2.01) and ESKD (aRR, 3.64; 95% CI, 2.34-5.66). Preterm preeclampsia was associated with increased risk of ESKD (aRR, 5.66; 95% CI, 3.06-10.48); this association with ESKD persisted for women who had preterm deliveries without preeclampsia (aRR, 2.09; 95% CI, 1.64-2.66). Gestational diabetes was associated with increased risk of CKD among black women (aRR, 1.78; 95% CI, 1.18-2.70), but not white women (aRR, 0.81; 95% CI, 0.58-1.13)., Conclusions and Relevance: In this meta-analysis, exposure to adverse pregnancy outcomes, including hypertensive disorders of pregnancy, gestational diabetes, and preterm delivery, was associated with higher risk of long-term kidney disease. The risk of ESKD was highest among women who experienced preeclampsia. A systematic approach may be warranted to identify women at increased risk of kidney disease, particularly after hypertensive disorders of pregnancy, and to optimize their long-term follow-up.

Background: Preeclampsia has been suggested to increase the risk of end-stage kidney disease (ESKD); however, most studies were unable to adjust for potential confounders including pre-existing comorbidities such as renal disease and cardiovascular disease (CVD). We aimed to examine the association between preeclampsia and the risk of ESKD in healthy women, while taking into account pre-existing comorbidity and potential confounders., Methods and Findings: Using data from the Swedish Medical Birth Register (MBR), women who had singleton live births in Sweden between 1982 and 2012, including those who had preeclampsia, were identified. Women with a diagnosis of chronic kidney disease (CKD), CVD, hypertension, or diabetes prior to the first pregnancy were excluded. The outcome was a diagnosis of ESKD, identified from the Swedish Renal Registry (SRR) from January 1, 1991, onwards along with the specified cause of renal disease. We conducted Cox proportional hazards regression analysis to examine the association between preeclampsia and ESKD adjusting for several potential confounders: maternal age, body mass index (BMI), education, native country, and smoking. This analysis accounts for differential follow-up among women because women had different lengths of follow-up time. We performed subgroup analyses according to preterm preeclampsia, small for gestational age (SGA), and women who had 2 pregnancies with preeclampsia in both. The cohort consisted of 1,366,441 healthy women who had 2,665,320 singleton live births in Sweden between 1982 and 2012. At the first pregnancy, women's mean (SD) age and BMI were 27.8 (5.13) and 23.4 (4.03), respectively, 15.2% were smokers, and 80.7% were native Swedish. The overall median (interquartile range [IQR]) follow-up was 7.4 years (3.2-17.4) and 16.4 years (10.3-22.0) among women with ESKD diagnosis. During the study period, 67,273 (4.9%) women having 74,648 (2.8% of all pregnancies) singleton live births had preeclampsia, and 410 women developed ESKD with an incidence rate of 1.85 per 100,000 person-years. There was an association between preeclampsia and ESKD in the unadjusted analysis (hazard ratio [HR] = 4.99, 95% confidence interval [CI] 3.93-6.33; p < 0.001), which remained in the extensively adjusted (HR = 4.96, 95% CI 3.89-6.32, p < 0.001) models. Women who had preterm preeclampsia (adjusted HR = 9.19; 95% CI 5.16-15.61, p < 0.001) and women who had preeclampsia in 2 pregnancies (adjusted HR = 7.13, 95% CI 3.12-16.31, p < 0.001) had the highest risk of ESKD compared with women with no preeclampsia. Considering this was an observational cohort study, and although we accounted for several potential confounders, residual confounding cannot be ruled out., Conclusions: The present findings suggest that women with preeclampsia and no major comorbidities before their first pregnancy are at a 5-fold increased risk of ESKD compared with parous women with no preeclampsia; however, the absolute risk of ESKD among women with preeclampsia remains small. Preeclampsia should be considered as an important risk factor for subsequent ESKD. Whether screening and/or preventive strategies will reduce the risk of ESKD in women with adverse pregnancy outcomes is worthy of further investigation., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: ME has participated in an advisory board meeting (Astellas) and has received payment for lectures by Astellas in the field of renal anemia. LCK is a minority shareholder in Metabolomic Diagnostics, a company which has licenced IP pertaining to the early pregnancy prediction of biomarkers to predict pre-eclampsia. LCK has also given talks about pre-eclampsia at symposia sponsored by Roche and Alere.

Introduction: Adverse pregnancy outcomes, such as hypertensive disorders of pregnancy (HDP), gestational diabetes (GDM) and preterm birth have been linked to maternal cardiovascular disease in later life. Pre-eclampsia (PE) is associated with an increased risk of postpartum microalbuminuria, but there is no clear consensus on whether HDP increases the risk of maternal chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Similarly, it is uncertain whether GDM, preterm birth and delivery of low birth-weight infants independently predict the risk of maternal renal disease in later life. The aims of this proposed systematic review and meta-analysis are to summarise the available evidence examining the association between adverse outcomes of pregnancy (HDP, GDM, preterm birth, delivery of low birth-weight infant) and later maternal renal disease and to synthesise the results of relevant studies., Methods and Analysis: A systematic search of PubMed, EMBASE and Web of Science will be undertaken using a detailed prespecified search strategy. Two authors will independently review the titles and abstracts of all studies, perform data extraction and appraise the quality of included studies using a bias classification tool. Original case-control and cohort studies published in English will be considered for inclusion. Primary outcomes of interest will be CKD and ESKD; secondary outcomes will be hospitalisation for renal disease and deaths from renal disease. Meta-analyses will be performed to calculate the overall pooled estimates using the generic inverse variance method. The systematic review will follow the Meta-analyses Of Observational Studies in Epidemiology guidelines., Ethics and Dissemination: This systematic review and meta-analysis will be based on published data, and thus there is no requirement for ethics approval. The results will be shared through publication in a peer reviewed journal and through presentations at academic conferences., Prospero Registration Number: CRD42018110891., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Invasive fetal therapy  Invasive fetal therapy in Sweden consists of fetoscopic interventions to treat twin-to-twin transfusion syndrome (TTS) or twin anemia polycytemia sequence (TAPS) in monochorionic twin or triplet pregnancies and for selective reduction in monochorionic twins complicated by discordant anomalies or severe growth retardation in one fetus. Alternative methods, such as intrafetal laser ablation and radio frequency ablation, are also used for selective reduction and rarely to treat fetal tumors. Ultrasound guided intrauterine blood transfusions to treat fetal anemia have been performed for a long time with excellent results. Placement of thoraco-amniotic shunts and vesico-amniotic shunts is indicated in a few cases per year in Sweden. Since these rare interventions were centralized to one national center in 2013, the outcome of the fetal interventions has improved consistently.

Amniotic fluid (AF) surrounds the growing fetus, and cells derived from AF are commonly used for diagnosis of genetic diseases. Intra-amniotic infections are strongly linked to preterm birth, which is the leading cause of perinatal mortality worldwide. Surprisingly little is known, however, about mature hematopoietic cells in AF, which could potentially be involved in immune responses during pregnancy. In this study, we show that the dominating population of viable CD45 + cells in AF is represented by a subset of fetal CD103 + group 3 innate lymphoid cells (ILCs) producing high levels of IL-17 and TNF. Fetal CD103 + ILC3s could also be detected at high frequency in second-trimester mucosal tissues (e.g., the intestine and lung). Taken together, our data indicate that CD103 + ILC3s accumulate with gestation in the fetal intestine and subsequently egress to the AF. The dominance of ILC3s producing IL-17 and TNF in AF suggests that they could be involved in controlling intra-amniotic infections and inflammation and as such could be important players in regulating subsequent premature birth., (Copyright © 2016 by The American Association of Immunologists, Inc.)

Objective: To investigate pregnancy outcome for fetuses with nuchal translucency (NT) ≥3.5 mm but normal karyotype in the Stockholm (Sweden) area., Methods: A retrospective population-based cohort study. From 2006 to 2012, fetal NT was measured in 55123 singleton pregnancies. There were 341 pregnancies with NT thickness ≥3.5 mm; 139 had a normal karyotype, 164 had an abnormal karyotype and 38 were removed from the study. Pregnancy outcome was defined as adverse (termination of pregnancy [TOP], miscarriage [MC], intrauterine fetal death [IUFD], or delivery of a child with structural defects or genetic disorders), or favourable (delivery of a child without any structural defects or genetic disorders diagnosed before discharge)., Results: Of the 139 high NT pregnancies with normal karyotype, 110 (79.2%) resulted in live births, one (0.7%) IUFD, 23 (16.5%) TOP and five (3.6%) MC. The risk of an adverse pregnancy outcome increased with increasing NT. Structural fetal defects were found in 28 (19.5%) of pregnancies undergoing second trimester ultrasound screening, of which seven resulted in live births and 21 were terminated. The most common structural defect was cardiac defects., Conclusions: Adverse pregnancy outcome increased with increasing NT, even with normal karyotype, however, the prognosis is good if the second trimester ultrasound screening is normal., (© The Author(s) 2015.)

Objective: To evaluate the performance and cost efficacy of different first-trimester contingent screening strategies based on an initial analysis of biochemical markers., Design: Retrospective study., Setting: Swedish National Quality Register for prenatal diagnosis., Population: 35,780 women with singleton pregnancies., Methods: Serum values from first trimester biochemistry were re-analyzed in a contingent approach. For risks between 1:40 and 1:1000, risk estimates from nuchal translucency measurements were added and outcomes were compared using either a final cut-off risk of 1:200 to proceed with invasive testing or offering non-invasive prenatal testing. In a subgroup of 12,836 women with regular menstrual cycles the same analyses were performed using data on the last menstrual period for determining gestational age. The costs of detecting one case of aneuploidy were compared., Main Outcome Measures: Comparison of screening strategies., Results: The detection rate was the same (87%) in the contingent group as in complete combined screening, with only 41% requiring a nuchal translucency scan. As an alternative, offering non-invasive prenatal testing to the intermediate risk group would result in a detection rate of 98%, but the cost to detect one case of trisomy 21 would be 83% higher than the cost associated with traditional combined screening., Conclusions: First trimester examination using a contingent approach will achieve similar results compared with full combined screening. Non-invasive prenatal testing will not be cost-effective when a high proportion of pregnancies need further testing., (© 2015 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To compare causes of stillbirth in preterm and term pregnancies., Design: Cohort study., Setting: All delivery wards in Stockholm, 1998-2009., Population: Stillbirths from singleton pregnancies of gestational age ≥22(+0) (n = 1089) extracted from a web-based database including all stillbirths in the major Stockholm area since 1998., Methods: The parents of the stillborns were all offered an extensive standardized investigation. The causes of death were assigned in a perinatal audit using the Stockholm classification of stillbirth. Singleton stillbirths were divided into preterm (gestational week 22(+0) -36(+6) ) and term/post-term (gestational week ≥37(+0) ). The term/post-term group was subdivided into term (gestational week 37(+0) -40(+6) ) and post-term stillbirths (gestational week ≥41(+0) )., Main Outcome Measure: Causes of stillbirth at different gestational ages., Results: A higher proportion of placental abruption and preeclampsia/hypertension was seen in preterm stillbirths compared with term/post-term stillbirths, which instead had a higher proportion of umbilical cord complications and infection. Infection was more common in post-term than term stillbirths (46.5 vs. 19.8%, p < 0.001)., Conclusion: Increased knowledge of causes of stillbirth in different gestational ages may be valuable in developing strategies for prevention of fetal death. The high proportion of infection in post-term stillbirths could be clinically important and warrants further studies., (© 2013 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: The aim of this study was to compare placental findings from early preterm stillbirths with gestational week-matched liveborn infants. The main focus was to investigate the differences in the presence and distribution of inflammatory signs in the placentas of these two groups, especially referring to histological acute chorioamnionitis (CAM)., Methods: A case-control study of preterm stillbirths, between 22 and 32 weeks gestation, here referred to as early preterm, (cases, n = 112) and gestational week-matched liveborn infants (references, n = 166) in Stockholm. Relevant clinical data were collected from a web-based database (for cases) and delivery records (for references). Macroscopic and histological examinations of placentas were performed according to a structured protocol (placental weight relative to gestational age, accelerated villous maturation, infarction, intervillous thrombosis, foetal thrombosis, chronic villitis and CAM (polymorphonuclear leucocytes in the chorion/amnion), with and without foetal inflammatory responses (FIRs) (vasculitis in placental and/or cord vessels and funisitis). Statistical analyses were performed using a multivariable logistic regression., Results: Small for gestational age (AOR: 2.13, CI: 1.26-3.62) and CAM without a FIR (AOR: 2.44, CI: 1.10-5.41) were associated with an elevated risk of preterm stillbirth., Conclusions: Histological acute CAM without a FIR is associated with a higher risk for stillbirth in early preterm pregnancies.

Objective: To describe the establishment of the fetoscopic guided laser occlusion (FLOC) technique for treatment of twin-to-twin transfusion syndrome (TTTS) and the initial results in a Swedish national center., Design: Retrospective, descriptive study., Setting: Tertiary level university hospital., Population: All referred and treated cases suffering significant TTTS., Methods: The present study includes all cases of FLOC for TTTS at the Center of Fetal Medicine at Karolinska University Hospital, Stockholm, Sweden from October 2001 until December 2009. Patients were referred from all over Sweden and a few from other Nordic countries. The patients were evaluated with ultrasound examination between gestational ages of 18 and 26 weeks. Data from patients were extracted from our electronic medical record system and, in addition, families were contacted and medical records requested from referring hospitals., Main Outcome Measures: Pregnancies with one or more surviving infants after FLOC treatment categorized according to stage of TTTS., Results: In 75% of pregnancies, one or more infant was born alive. At stage I, both infants survived in one pregnancy and one survived in the second. There was no significant difference between cases at stage II or III, i.e. 73 vs. 78% of pregnancies resulted in one or more surviving infant. At stage IV, 66% of pregnancies ended with one or more surviving infant., Conclusions: Treatment of TTTS is feasible in a rather small country like Sweden, with comparable results to other centers. There are strong arguments for centralization and further improvement of this kind of highly specialized treatment., (© 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.)

Aim: To determine infant survival and neonatal outcome after fetoscopic laser treatment of twin-to-twin transfusion syndrome (TTTS)., Results: In 53/71(75%) laser-treated TTTS cases, at least one twin was liveborn and in 42/71(59%) cases at least one twin survived infancy. Fetal survival did not differ between donors [41/71(58%)] and recipients [46/71(65%), P=0.36]. Among liveborns, infant survival was 29/41(71%) in donors and 36/46(78%) in recipients (P=0.12). Infant survival did not correlate to maternal characteristics (age, BMI, smoking or parity), gestational age at treatment or severity of TTTS (Quintero stage). No TTTS infant born before 25 weeks of gestation survived the first week. Among the 87 infant survivors, 26 (30%) had an Apgar score <7 at 5 min, 47 (54%) developed respiratory distress syndrome, 10 (11%) showed signs of severe brain damage, nine (10%) renal failure, eight (9%) bronchopulmonary dysplasia, and five (6%) infants developed retinopathy of prematurity ≥stage 3. There was no significant difference in neonatal morbidity between recipients and donors., Conclusions: Fetal survival after laser treatment was comparable to that reported by other international centers. There was no significant difference in survival or neonatal morbidity between donors and recipients. Major neonatal morbidity was common, and combined with extremely preterm delivery the prognosis of TTTS is poor.

Objective: To evaluate the performance of a new first trimester web-based software for the detection of chromosomal anomalies using a combination of ultrasound and biochemistry., Design: Registry-based cohort study., Setting: Ultrasound units in the Stockholm region., Population: 20 710 women with singleton pregnancies were examined at 11(+0) to 13(+6) weeks' gestational age during a three-year period 2006-2009., Methods: The risks for trisomy 21, 13 and 18 were calculated using a combination of maternal age, serum markers and nuchal translucency. Individual risk estimates were calculated and then reported to a web-based system using a new algorithm based on likelihood ratios of each marker derived from Gaussian distributions in normal and affected pregnancies., Main Outcome Measures: The impact on rates of invasive testing and the incidence of children born with Down's syndrome after implementing the method., Results: Approximately a third of all pregnant women in the region were examined with the combined test. The detection and test positive rates for Down's syndrome was 90 and 6.8%, respectively. Invasive testing among pregnant women decreased from 15 to 8% after introducing the method but the incidence of children born with Down's syndrome did not decrease during the study period., Conclusion: The new web-based software is an effective method for the detection of trisomy 21 with similar performance compared to other programs. However, it needs to be offered to all pregnant women to have an impact on the incidence of Down's syndrome., (© 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2011 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To elucidate differences in the frequency and severity of acute chorioamnionitis (CAM) and chronic villitis in placentas from stillborns compared with liveborns at term and to evaluate other risk factors and placental findings., Design: Case-control study., Setting: All delivery wards in major Stockholm area. Population or Sample. Placentas from stillborn/case (n = 126) and liveborn/control (n = 273) neonates were prospectively collected between 2002 and 2005., Methods: CAM was assessed on a three-grade scale based on the presence and distribution of polymorphonuclear leucocytes in the chorion/amnion. The presence of vasculitis and funisitis was recorded separately. Chronic villitis was diagnosed by the presence of mononuclear cells in the villous stroma. Relevant clinical data were collected from a specially constructed, web-based database. The statistic analyses were performed using multivariable logistic regression., Results: CAM (especially severe, AOR: 7.39 CI: 3.05-17.95), villous immaturity (AOR: 7.17 CI: 2.66-19.33), villitis (<1 % AOR: 4.31 CI: 1.16-15.98; ≥ 1 %, AOR: 3.87 CI: 1.38-10.83), SGA (AOR: 7.52 CI: 3.06-18.48), and BMI >24.9 (AOR: 2.06 CI: 1.21-3.51) were all connected to an elevated risk of term stillbirth., Conclusions: We found that CAM, chronic villitis, villous immaturity, SGA, and maternal overweight, but not vasculitis or funisitis are independently associated with risk for stillbirth at term.

Objective: To generate a regression equation for the nuchal translucency (NT) median for the Swedish population and compare this with other median values., Setting: Eight Swedish hospitals., Sample: The data set included 20 887 unaffected fetuses., Methods: Calculation and generation of an NT centile chart for the Swedish population., Results: The NT centiles for crown-rump length (CRL) from 45 to 84 mm were calculated and compared with the medians from Glasgow, from the Fetal Medicine Foundation (FMF, London, UK; FMF-original) and those published recently (FMF-new). The NT medians cease to increase at CRLs between 70 and 75 mm. The Swedish, FMF-new and Glasgow medians followed the same pattern, but the Glasgow NT median curve was systematically lower by around 20%. Swedish, FMF-new and Glasgow medians differed in shape from the FMF-original medians, which continuously increase throughout the whole range of CRLs., Conclusions: Our results demonstrate that there are substantial differences in the NT medians and centiles between countries., (© 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.)

Introduction: We present a review of all cases of intravascular transfusions in red cell alloimmunization over a time span of 20 years in Stockholm. The aim of the study is to compare our results with published results from larger centers and to identify areas that can be further improved., Material and Methods: A retrospective cohort study was conducted of all women treated with intrauterine transfusions due to erythrocyte immunization in our hospital between June 1990 and June 2010. Primary outcome variables were fetal and neonatal survival, procedure-related complications and gestational age at delivery., Results: A total of 284 intrauterine transfusions were performed in 84 pregnancies, with an overall survival rate of 91.8%. Procedure-related and fatal complications occurred in the present study in 4.9 and 1.4% of fetuses or neonates, respectively. Procedure-related complications were significantly more common in free-loop transfusions than in transfusions in the intrahepatic part of the umbilical vein (OR: 5.4, p = 0.025). There was no significant difference between the intrahepatic and the placental cord insertion route (p = 0.83). Gestational age at first transfusion was significantly associated with an increased risk of a procedure-related complication (OR: 0.8, p = 0.019). Of the live-born infants, 24% of the neonates were born before gestational week 34., Discussion: Our study confirms previous studies demonstrating favorable results with intravascular transfusions., (Copyright © 2011 S. Karger AG, Basel.)

This ex vivo study focuses on the mechanisms of endothelium-dependent dilatation in the uterine circulation of normal pregnancy (n = 12) and in women with preeclampsia (n = 12). Arteries (internal diameter, ∼250 μm) isolated by myometrial biopsy from women undergoing planned cesarean delivery or delivery as a result of the deterioration of preeclampsia were studied using a wire myograph. Bradykinin-induced dilatation was assessed in the presence and/or absence of pharmacological inhibitors to determine the contribution of nitric oxide and endothelium-derived hyperpolarizing factor (EDHF), as well as that of EDHF-mediated pathways such as myoendothelial gap junctions (MEGJs) and products of arachidonic acid, H(2)O(2) and cytochrome P450 2C9 (CYP2C9). Transmission electron microscopy was used to visualize morphological prerequisites for MEGJs. In normal pregnancy, EDHF through MEGJs appeared to be a predominant mediator conferring endothelium-dependent relaxation in small myometrial arteries. In preeclampsia, bradykinin-induced relaxation was reduced via compromised EDHF-type responses, in which the contribution of MEGJs became negligible. The attenuated role of MEGJs to endothelium-dependent relaxation was partly compensated through the contribution of H(2)O(2) or other endothelium-derived relaxing factors. CYP2C9 products of arachidonic acid had no effect on EDHF-type relaxation in arteries of women with normal pregnancy or with preeclampsia. We suggest that EDHF-type responses via MEGJs are primarily targeted in small myometrial arteries in women with preeclampsia. This could significantly contribute to the impaired uteroplacental blood flow in this disorder.

Objective: To develop an indicator of maternal near miss as a proxy for maternal death and to study its association with maternal factors and perinatal outcomes., Methods: In a multicenter cross-sectional study, we collected maternal and perinatal data from the hospital records of a sample of women admitted for delivery over a period of two to three months in 120 hospitals located in eight Latin American countries. We followed a stratified multistage cluster random design. We assessed the intra-hospital occurrence of severe maternal morbidity and the latter's association with maternal characteristics and perinatal outcomes., Findings: Of the 97,095 women studied, 2964 (34 per 1000) were at higher risk of dying in association with one or more of the following: being admitted to the intensive care unit (ICU), undergoing a hysterectomy, receiving a blood transfusion, suffering a cardiac or renal complication, or having eclampsia. Being older than 35 years, not having a partner, being a primipara or para > 3, and having had a Caesarean section in the previous pregnancy were factors independently associated with the occurrence of severe maternal morbidity. They were also positively associated with an increased occurrence of low and very low birth weight, stillbirth, early neonatal death, admission to the neonatal ICU, a prolonged maternal postpartum hospital stay and Caesarean section., Conclusion: Women who survive the serious conditions described could be pragmatically considered cases of maternal near miss. Interventions to reduce maternal and perinatal mortality should target women in these high-risk categories.

Objective: To assess the association between cesarean delivery rates and pregnancy outcomes in African health facilities., Methods: Data were obtained from all births over 2-3 months in 131 facilities. Outcomes included maternal deaths, severe maternal morbidity, fresh stillbirths, and neonatal deaths and morbidity., Results: Median cesarean delivery rate was 8.8% among 83439 births. Cesarean deliveries were performed in only 95 (73%) facilities. Facility-specific cesarean delivery rates were influenced by previous cesarean, pre-eclampsia, induced labor, referral status, and higher health facility classification scores. Pre-eclampsia increased the risks of maternal death, fresh stillbirths, and severe neonatal morbidity. Adjusted emergency cesarean delivery rate was associated with more fresh stillbirths, neonatal deaths, and severe neonatal morbidity--probably related to prolonged labor, asphyxia, and sepsis. Adjusted elective cesarean delivery rate was associated with fewer perinatal deaths., Conclusion: Use of cesarean delivery is limited in the African health facilities surveyed. Emergency cesareans, when performed, are often too late to reduce perinatal deaths.

Objective: To provide the necessary mathematical formulae to construct a risk calculation package for Down's syndrome using maternal serum free beta human chorionic gonadotrophin, pregnancy associated plasma protein A, and ultrasound nuchal translucency(NT) measurements in the first trimester for use in a web-based system., Setting: Swedish antenatal screening program., Population: Swedish women choosing to have first trimester screening for Down's syndrome., Methods: A standard Gaussian approach to calculation of likelihood ratios for each marker value was used following conversion of analyte concentrations and NT measurements to multiples of the normal gestational median (MoM). Validation of the algorithm was carried out on a study group of 3,900 pregnancies (including 29 cases of Down's syndrome). Predicted detection and screen positive rates were compared with an alternative calculation package., Main Outcome Measures: Sensitivity and specificity of screening delivered by risk calculation package., Results: A cut-off risk of 1 in 200 produced a detection rate of 90% at a 4.7% false-positive rate. In addition, use of the calculation package in a web-based system proved efficient in routine practice, providing rapid access by individual centers to results and easy central monitoring and auditing of the program., Conclusions: The system described here fulfills the requirement for an appropriately validated risk calculation package, is fully user configurable with easy access through a web-based system allowing extension of the screening program to multiple centers.

Cluster-based studies involving aggregate units such as hospitals or medical practices are increasingly being used in healthcare evaluation. An important characteristic of such studies is the presence of intracluster correlation, typically quantified by the intracluster correlation coefficient (ICC). Sample size calculations for cluster-based studies need to account for the ICC, or risk underestimating the sample size required to yield the desired levels of power and significance. In this article, we present values for ICCs that were obtained from data on 97,095 pregnancies and 98,072 births taking place in a representative sample of 120 hospitals in eight Latin American countries. We present ICCs for 86 variables measured on mothers and newborns from pregnancy to the time of hospital discharge, including 'process variables' representing actual medical care received for each mother and newborn. Process variables are of primary interest in the field of implementation research. We found that overall, ICCs ranged from a minimum of 0.0003 to a maximum of 0.563 (median 0.067). For maternal and newborn outcome variables, the median ICCs were 0.011 (interquartile range 0.007-0.037) and 0.054 (interquartile range 0.013-0.075) respectively; however, for process variables, the median was 0.161 (interquartile range 0.072-0.328). Thus, we confirm previous findings that process variables tend to have higher ICCs than outcome variables. We demonstrate that ICCs generally tend to increase with higher prevalences (close to 0.5). These results can help researchers calculate the required sample size for future research studies in maternal and perinatal health.

We hypothesized that in preeclampsia (PE), contribution of endothelium-derived hyperpolarizing factor (EDHF) and the mechanism/s of its action differ from that in normal pregnancy (NP). We aimed to assess endothelial function and morphology in arteries from NP and PE with particular focus on EDHF. Arteries ( approximately 200 mum) were dissected from subcutaneous fat biopsies obtained from women undergoing cesarean section. With the use of wire myography, responses to the endothelium-dependent agonist bradykinin (BK) were determined before and after inhibition of pathways relevant to EDHF activity. The overall responses to BK in arteries from PE (n = 13) and NP (n = 17) were similar. However, in PE, EDHF-mediated relaxation was reduced (P < 0.05). All women within the PE group were divided into two subgroups: with more (group 1) or less (group 2) than 50% reduction of EDHF-typed responses after 18-alpha-glycyrrhetinic acid (an inhibitor of myoendothelial gap junctions, MEGJs). The division showed that 1) MEGJs are principally involved when the EDHF contribution is reduced; and 2) when the EDHF contribution is similar to that in NP, the H(2)O(2) and/or cytochrome P-450 epoxygenase products of arachidonic acid (AA), along with MEGJs, confer EDHF-mediated relaxation. In contrast, MEGJs were the main pathway for EDHF in NP. The abundant presence of MEGJs in arteries from NP but deficiency of them in PE was observed using transmission electron microscopy. We conclude that PE is associated with heterogeneous contribution of EDHF, and the mechanism behind EDHF-typed responses is mediated either by MEGJs alone or in combination with H(2)O(2) or cytochrome P-450 epoxygenase metabolites of AA.

Objective: To set up a global system for monitoring maternal and perinatal health in 54 countries worldwide., Methods: The WHO Global Survey for Monitoring Maternal and Perinatal Health was implemented through a network of health institutions, selected using a stratified multistage cluster sampling design. Focused information on maternal and perinatal health was abstracted from hospital records and entered in a specially developed online data management system. Data were collected over a two- to three-month period in each institution. The project was coordinated by WHO and supported by WHO regional offices and country coordinators in Africa and the Americas., Findings: The initial survey was implemented between September 2004 and March 2005 in the African and American regions. A total of 125 institutions in seven African countries and 119 institutions in eight Latin American countries participated., Conclusion: This project has created a technologically simple and scientifically sound system for large-scale data management, which can facilitate programme monitoring in countries.

Objective: To design and validate a classification system for audit groups working with stillbirth. The classification includes well-defined primary and associated conditions related to fetal death., Design: Descriptive., Setting: All delivery wards in Stockholm., Population: Stillbirths from 22 completed weeks in Stockholm, Sweden., Methods: Parallel to audit work, the Stockholm stillbirth group has developed a classification of conditions related to stillbirth. The classification has been validated., Main Outcome Measure: The classification and the results of the validation are presented., Result: The classification with 17 groups identifying underlying conditions related to stillbirth (primary diagnoses) and associated factors which may have contributed to the death (associated diagnoses) is described. The conditions are subdivided into definite, probable and possible relation to the death. An evaluation of 382 cases of stillbirth during 2002-2005 resulted in 382 primary diagnoses and 132 associated diagnoses. The most common conditions identified were intrauterine growth restriction/placental insufficiency (23%), infection (19%), malformations/chromosomal abnormalities (12%). The 'unexplained' group together with the 'unknown' group comprised 18%. Validation was done by reclassification of 95 cases from 2005 by six investigators. The overall agreement regarding primary diagnosis was substantial (kappa=0.70)., Conclusions: The Stockholm classification of stillbirth consists of 17 diagnostic groups allowing one primary diagnosis and if needed, associated diagnoses. Diagnoses are subdivided according to definite, probable and possible relation to stillbirth. Validation showed high degree of agreement regarding primary diagnosis. The classification can provide a useful tool for clinicians and audit groups when discussing cause and underlying conditions of fetal death.

Objective: To compare ultrasound (US) and fetal autopsy findings in 2(nd) trimester termination of pregnancy because of structural fetal anomalies., Methods: A total of 112 terminations of pregnancy (TOP) between 1999-2003 were reviewed retrospectively. The cases originated from a secondary and a tertiary Fetal Medicine unit in the south Stockholm area, using a common specialized perinatal pathology service. Karyotype was not known at the time of US examination. The findings were compared and classified into four groups according to the degree of agreement between US and autopsy., Results: In 45% of cases there was total agreement between US and autopsy. In 40%, autopsy confirmed all US findings but provided additional information of clinical importance. Partial or total lack of agreement was noted in 11% and 4% of the cases, respectively. Areas of discrepancy involved mainly CNS- and cardiovascular abnormalities and, to a lesser extent, renal anomalies, abdominal wall defects and hydrops/hygroma. Regarding CNS abnormalities the overall rate of agreement was 62%; it was highest in acrania/anencephaly (92%) and lowest in hydrocephaly (39%)., Conclusion: We find an overall high degree of agreement between US and autopsy findings. Autopsy often provided additional information of clinical value and it should always follow US examination and TOP. Fixation of CNS is crucial for optimal results. Specific limitations of autopsy, i.e., detection of CNS abnormalities, may be reduced by complementary imaging techniques, such as MRI. The ability of US to detect cardiac anomalies is enhanced with the close contact to specialized fetal cardiology.

Objective: To assess the risks and benefits associated with caesarean delivery compared with vaginal delivery., Design: Prospective cohort study within the 2005 WHO global survey on maternal and perinatal health., Setting: 410 health facilities in 24 areas in eight randomly selected Latin American countries; 123 were randomly selected and 120 participated and provided data, Participants: 106,546 deliveries reported during the three month study period, with data available for 97,095 (91% coverage)., Main Outcome Measures: Maternal, fetal, and neonatal morbidity and mortality associated with intrapartum or elective caesarean delivery, adjusted for clinical, demographic, pregnancy, and institutional characteristics., Results: Women undergoing caesarean delivery had an increased risk of severe maternal morbidity compared with women undergoing vaginal delivery (odds ratio 2.0 (95% confidence interval 1.6 to 2.5) for intrapartum caesarean and 2.3 (1.7 to 3.1) for elective caesarean). The risk of antibiotic treatment after delivery for women having either type of caesarean was five times that of women having vaginal deliveries. With cephalic presentation, there was a trend towards a reduced odds ratio for fetal death with elective caesarean, after adjustment for possible confounding variables and gestational age (0.7, 0.4 to 1.0). With breech presentation, caesarean delivery had a large protective effect for fetal death. With cephalic presentation, however, independent of possible confounding variables and gestational age, intrapartum and elective caesarean increased the risk for a stay of seven or more days in neonatal intensive care (2.1 (1.8 to 2.6) and 1.9 (1.6 to 2.3), respectively) and the risk of neonatal mortality up to hospital discharge (1.7 (1.3 to 2.2) and 1.9 (1.5 to 2.6), respectively), which remained higher even after exclusion of all caesarean deliveries for fetal distress. Such increased risk was not seen for breech presentation. Lack of labour was a risk factor for a stay of seven or more days in neonatal intensive care and neonatal mortality up to hospital discharge for babies delivered by elective caesarean delivery, but rupturing of membranes may be protective., Conclusions: Caesarean delivery independently reduces overall risk in breech presentations and risk of intrapartum fetal death in cephalic presentations but increases the risk of severe maternal and neonatal morbidity and mortality in cephalic presentations.

Background: Caesarean delivery rates continue to increase worldwide. Our aim was to assess the association between caesarean delivery and pregnancy outcome at the institutional level, adjusting for the pregnant population and institutional characteristics., Methods: For the 2005 WHO global survey on maternal and perinatal health, we assessed a multistage stratified sample, comprising 24 geographic regions in eight countries in Latin America. We obtained individual data for all women admitted for delivery over 3 months to 120 institutions randomly selected from of 410 identified institutions. We also obtained institutional-level data., Findings: We obtained data for 97,095 of 106,546 deliveries (91% coverage). The median rate of caesarean delivery was 33% (quartile range 24-43), with the highest rates of caesarean delivery noted in private hospitals (51%, 43-57). Institution-specific rates of caesarean delivery were affected by primiparity, previous caesarean delivery, and institutional complexity. Rate of caesarean delivery was positively associated with postpartum antibiotic treatment and severe maternal morbidity and mortality, even after adjustment for risk factors. Increase in the rate of caesarean delivery was associated with an increase in fetal mortality rates and higher numbers of babies admitted to intensive care for 7 days or longer even after adjustment for preterm delivery. Rates of preterm delivery and neonatal mortality both rose at rates of caesarean delivery of between 10% and 20%., Interpretation: High rates of caesarean delivery do not necessarily indicate better perinatal care and can be associated with harm.

Background: The objective was to study fetal growth parameters in in vitro fertilization (IVF) pregnancies and to investigate the relationship between fetal growth and maternal blood pressure., Methods: We examined 64 women, pregnant after in vitro fertilization, with repeated ultrasound examinations measuring biparietal diameter, femur length, abdominal diameter and fetal weight at 24, 30, and 36 weeks of gestation. We calculated deviations in percent from expected values in regards to biparietal diameter, femur length, abdominal diameter, and fetal weight. Blood pressure was measured every second week., Results: Biparietal diameter in the study group was significantly smaller at 24 (-3.3%, 95%CI -4.4 to -2.2) and 30 (-1.4%; 95%CI -2.5% to -0.3) weeks. Femur length differed significantly on all three occasions, at 24 (-6.3%; 95%CI -7.7 to -5.1), 30 (-6.6%; 95%CI -8.0 to -5.3), and 36 (-3.9%; 95%CI; -5.0 to -2.8) weeks. Abdominal diameter demonstrated a significant deviation at 24 weeks (-1.6%; 95%CI -2.8 to -0.4). Fetal weight did not reach significant deviations at any gestational age. There was no correlation between deviation of the individual growth parameters or estimated fetal weight and elevated blood pressure., Conclusion: The growth pattern of in vitro fertilization pregnancies does not seem to differ from spontaneously conceived pregnancies to any appreciable extent. In the present material, no relationship between fetal growth and maternal blood pressure could be observed. We could not show that an impaired fetal growth predates the development of hypertension.

Aims: To describe and evaluate the use of an Internet-based study protocol in a multicentre study of genetic risk factors in anticoagulant treatment., Methods: A web-based study protocol, similar to existing anticoagulation medical record systems, was developed for entry of clinical data. It was also supplied with a separate interface for study monitoring. Measures were taken to assure the confidentiality of transferred data. In addition, software modifications were made to enable automated transfer of clinical data from an existing medical record system to the study database., Results: The system has been in use since March 2002, and at present 39 centres have included 909 patients with a dropout rate of 2.8%. The need for education of participating clinicians has been satisfactorily provided for by means of written instructions and telephone support., Conclusions: Our study demonstrates the usability of Internet-based data acquisition techniques in a full-scale multicentre clinical trial. The main advantages of such a protocol are automated data validation and standardization, fast data transfer independent of geographical distance, user feedback, synchronization of protocol updates and automatic data formatting facilitating statistical analyses. Safety and accessibility are possibly cumbersome areas and should be addressed duly.

Objective: To evaluate the use of an Internet-based information system on infectious disorders (INFPREG) in antenatal care in Sweden., Methods: A postal questionnaire was sent to all antenatal clinics in Sweden in 2000 (n = 515) and 2002 (n = 503). The questionnaire consisted of sections covering use of computers, availability of Internet connections and the use of INFPREG in patient care., Results: We received 404 completed questionnaires in 2000 and 501 in 2002. In 2000, 81% of the midwives had access to computers at their antenatal clinics, and this number had increased to 93% in 2002. Sixty-eight percent and 88% in 2000 and 2002, respectively, had computers with an Internet connection. Of the responding midwives, 74% in 2000 and 84% in 2002 had received information concerning INFPREG. In 2000, 29% of the midwives had visited INFPREG and this figure had increased to 58% in 2002. Of the midwives that had used INFPREG, 67% in 2000 and 81% in 2002 reported that the information obtained from the site was implemented in the patient care. Of the responders, 45% in 2000 and 43% in 2002 claimed that they needed more information on how to use INFPREG., Conclusions: A majority of midwives at antenatal clinics in Sweden have access to the Internet and are confident in using an Internet-based knowledge center on infectious disorders in pregnancy. The present study indicates a rapid acceptance among health care providers in antenatal care in Sweden of this new method for dissemination of information and guidelines. However, many midwives still want more information and knowledge on how to use an Internet-based information system.

With the development of the Internet technology, clinicians have got a valuable tool for solving some of the logistic problems affecting multicenter studies and registers. Web based solutions enhance efficiency and quality of multicenter studies. Data can be entered continuously without any time and geographical limitations. On-line connection to a central database improves involvement of participants, and information and alterations can easily be disseminated. The central database enables optimal randomization and stratification. Furthermore, web based IT solutions for studies and registers enable the patients to report their data directly into the database. Until now web based IT solutions have been rather expensive but may gradually come down in price.

Background: To evaluate the diagnostic methods and to elucidate the etiology of intrauterine fetal death., Material and Methods: A prospective study was conducted on all intrauterine fetal deaths occurring in Stockholm County in 1998-99. During a 24-month period, 188 cases of intrauterine fetal death with gestational ages of > or = 22 weeks were investigated in accordance with structured test protocol. All information from antenatal and delivery records as well as all test results were entered in to an Internet-based database for continuous evaluation., Results: A presumptive explanation to the stillbirth was established in 91% of the cases. The most common factors associated with intrauterine fetal death could be identified as infections (24%), placental insufficiency/intrauterine growth restriction (22%), placental abruption (19%), intercurrent maternal conditions (12%), congenital malformations (10%), and umbilical cord complications (9%)., Conclusions: A relevant test protocol in cases of intrauterine fetal death reduces the number of unexplained cases to a minimum. An Internet-based register on test results of fetal deaths may enable a continuous evaluation of the diagnostic tools and etiologic factors in an ever-changing panorama. The results from the present study can serve as a base for a case-control study in Sweden.