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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. Linked article: This article is commented on by Pisake Lumbiganon et al., pp. 1062‐1063 in this issue. To view this mini commentary visit https://doi.org/10.1111/1471‐0528.17795. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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: PlGFPerkinElmer = 0.553 (95% confidence interval [CI] 0.518–0.588) * PlGFRoche –1.112 (95% CI −2.773 to 0.550); r = 0.966, mean difference −24.6 (95% CI −26.4 to −22.8). PlGFPerkinElmer = 0.673 (95% CI 0.618–0.729) * PlGFThermoFisher –0.199 (95% CI −2.292 to 1.894); r = 0.945, mean difference −13.8 (95% CI −15.1 to −12.6). PlGFRoche = 1.809 (95% CI 1.694–1.923) * PlGFPerkinElmer +2.010 (95% CI −0.877 to 4.897); r = 0.966, mean difference 24.6 (95% CI 22.8–26.4). PlGFRoche = 1.237 (95% CI 1.113–1.361) * PlGFThermoFisher +0.840 (95% CI −3.684 to 5.363); r = 0.937, mean difference 10.8 (95% CI 9.4–12.1). PlGFThermoFisher = 1.485 (95% CI 1.363–1.607) * PlGFPerkinElmer +0.296 (95% CI −2.784 to 3.375); r = 0.945, mean difference 13.8 (95% CI 12.6–15.1). PlGFThermoFisher = 0.808 (95% CI 0.726–0.891) * PlGFRoche –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. [ABSTRACT FROM AUTHOR]

Author(s): Ali S. Khashan, Marie Evans, Marius Kublickas, Fergus P. McCarthy, Louise C. Kenny, Peter Stenvinkel, Tony Fitzgerald, Karolina Kublickiene In the Funding section, the following information was inadvertently omitted: [...]

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., Author(s): Ali S. Khashan 1,2,*, Marie Evans 3, Marius Kublickas 4, Fergus P. McCarthy 2,5, Louise C. Kenny 6, Peter Stenvinkel 3, Tony Fitzgerald 1,7, Karolina Kublickiene 3,* Introduction The [...]

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. Objectif Mettre au point un indicateur pour les deces maternels evites de justesse en tant qu'indicateur indirect des deces maternels et etudier son association avec des facteurs maternels et des evenements perinatals. Methodes Dans le cadre d'une etude transversale multicentrique, nous avons recueilli des donnees maternelles et perinatales a partir des dossiers hospitaliers d'un echantillon de femmes, constitue des parturientes admises pour accoucher dans 120 hopitaux appartenant a huit villes d'Amerique latine sur une periode de deux a trois mois. Nous avons applique une methode de sondage aleatoire stratifie a plusieurs degres et par grappe. Nous avons evalue l'occurrence en milieu hospitalier de ia morbidite maternelie severe et les associations de cette derniere avec les caracteristiques maternelles et les evenements perinatals. Resultats Sur les 97 095 femmes etudiees, 2964 (34 pour 1000) presentaient un risque important de deces en association avec une ou plusieurs des conditions suivantes : avoir ete admise dans une unite de soins intensifs, avoir subi une hysterectomie, avoir recu une transfusion sanguine, avoir souffert d'une complication cardiaque ou renale ou encore d'une eclampsie. Par ailleurs, avoir pius de 35 ans, ne pas avoir de partenaire, etre primipare ou quadripare et plus et avoir subi une cesarienne lors de la precedente grossesse etaient des facteurs independamment associes a l'occurrence de la morbidite maternelle severe. Ces facteurs etaient aussi positivement associes a une frequence accrue des petits poids et des tres petits poids de naissance, de la mortinatalite, des deces neonatals precoces, des admissions en soins intensifs neonatals, des sejours hospitaliers prolonges des meres pendant le postpartum et des cesariennes. Conclusion Les femmes qui survivent aux situations graves precedemment decrites peuvent etre considerees pratiquement comme des cas de deces maternel evite de justesse. Les interventions pour reduire la mortalite maternelle et perinatale doivent viser les femmes appartenant a ces categories a haut risque. Objetivo Elaborar un indicador de los cuasieventos maternos como medicion indirecta de las defunciones maternas y estudiar su relacion con diversos factores maternos y con Ios resultados perinatales. Metodos Mediante un estudio transversal multicentrico, a lo largo de un periodo de dos a tres meses reunimos datos maternos y perinatales de los registros hospitalarios de una muestra de mujeres ingresadas para dar a luz en 120 hospitales de ocho paises de America Latina. Aplicando un diseno aleatorio, polietapico, estratificado y por conglomerados, evaluamos les casos intrahospitalarios de morbilidad materna grave y la relacion entre esta y las caracteristicas de la madre y los resultados perinatales. Resultados De las 97 095 mujeres estudiadas, 2964 (34 por 1000) presentaron un mayor riesgo de morir asociado a alguno de los siguientes factores: ingreso en la unidad de cuidados intensivos, histerectomia, transfusion de sangre, complicacion cardiaca o renal, y eclampsia. Tener mas de 35 anos, carecer de pareja, ser primipara o acumular un minimo de tres partos anteriores y haber sido sometida a cesarea en el embarazo precedente fueron factores asociados independientemente a morbilidad materna grave. Se observo que estaban relacionados tambien positivamente con lo siguiente: un peso bajo o muy bajo al nacer, mortinatalidad, mortalidad neonatal precoz, ingreso en la UCI neonatal, estancia prolongada de la madre en el hospital tras el parto, y cesarea. Conclusion Los casos de las mujeres que sobreviven a los graves problemas aqui descritos pueden conceptuarse en la practica como cuasieventos maternos. Las intervenciones encaminadas a reducir la mortalidad materna y perinatal deberian focalizarse en las mujeres de esas categorias de riesgo., Introduction Approximately 15 000 women die every year in Latin America and the Caribbean of causes related to pregnancy. The maternal mortality ratio (MMR) for the region, which is around [...]

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 equal to] 200 [micro] m) 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 H202 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.sub.2][O.sub.2] or cytochrome P-450 epoxygenase metabolites of AA. gap junctions; small arteries; pregnancy

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. Objectif Mettre en place dans 54 pays repartis dans l&apos;ensemble du monde un systeme mondial de surveillance de la sante maternelle et perinatale. Methodes L&apos;Enquete mondiale sur la surveillance de la sante maternelle et perinatale de I&apos;OMS s&apos;est operee par le biais d&apos;un reseau d&apos;etablissements de soins, selectionnes par echantillonnage en grappe stratifie a plusieurs niveaux. Une information ciblee sur la sante maternelle et perinatale a ete extraite des registres hospitaliers et entree dans un systeme de gestion des donnees en ligne, specialement developpe. Les donnees ont ete recueillies sur une periode de deux a trois mois dans chaque etablissement. Le projet a ete coordonne par I&apos;OMS et appuye par les bureaux regionaux de I&apos;OMS et par ses coordinateurs nationaux en Afrique et dans les Ameriques. Resultats L&apos;enquete initiale a ete realisee entre septembre 2004 et mars 2005 en Afrique et dans les Ameriques. Ont participe au total a l&apos;enquete 125 etablissements de sept pays africains et 119 etablissements de huit pays d&apos;Amerique latine. Conclusion Ce projet a cree un systeme technologiquement simple et scientifiquement rigoureux pour la gestion grande echelle des donnees, pouvant faciliter la surveillance programmatique dans les pays. Objetivo Establecer un sistema mundial de vigilancia de la salud materna y perinatal en 54 paises de todo el mundo. Metodos La Encuesta mundial OMS de vigilancia de la salud materna y perinatal se llevo a cabo a traves de una red de instituciones sanitarias seleccionadas mediante muestreo polietapico estratificado por conglomerados. La informacion focalizada y resumida sobre la salud materna y perinatal extraida a partir de las historias clinicas se introdujo en un sistema de gestion de datos en linea especialmente desarrollado. A lo largo de un periodo de dos a tres meses se reunieron datos en cada institucion. El proyecto fue coordinado por la OMS y respaldado por las oficinas regionales de la OMS y los coordinadores en los paises en Africa y las Americas. Resultados La encuesta inicial se llevo a cabo entre septiembre de 2004 y marzo de 2005 en las regiones de Africa y de las Americas. Participaron en total 125 instituciones de siete paises africanos y 119 instituciones de ocho paises latinoamericanos. Conclusion Este proyecto ha generado un sistema tecnologicamente sencillo y cientificamente solido para gestionar datos a gran escala, lo cual puede facilitar la vigilancia de los programas en los paises. [TEXT NOT REPRODUCIBLE IN ASCII], Introduction The WHO Global Survey on Maternal and Perinatal Health aims to develop a network of health institutions worldwide that collects up-to-date information on services provided and on how evidence-based [...]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To compare ultrasound (US) and fetal autopsy findings in 2nd 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]