Association between socioeconomic status with pregnancy and neonatal outcomes:An international multicenter cohort

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.</p

Adverse pregnancy outcomes and long-term risk of maternal renal disease: a systematic review and meta-analysis protocol

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 CRD4201811089

Preeclampsia and risk of end stage kidney disease: A Swedish nationwide cohort study.

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

Cohort profile: Improved Pregnancy Outcomes via Early Detection (IMPROvED), an International Multicentre Prospective Cohort.

BackgroundImproved 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.MethodsA 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 dateClinical 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 plansIn 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

Cohort profile: Improved Pregnancy Outcomes via Early Detection (IMPROvED), an International Multicentre Prospective Cohort [version 3; peer review: 2 approved]

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

Maternal renaly artery doppler velocimetry in normal and hypertensive pregnancies

Maternal Renal Artery Doppler Velocimetry in Normal and Hypertensive Pregnancies by Marius KublickasBackground. The measurement of effective renalplasma flow (ERPF) by calculation of p-aminohippurate (PAH) clearance is an invasive,time-consuming procedure. In nonpregnant hu-mans, the clearance of isotopes can be used tomeasure renal plasma flow, but the use of theseradioactive substances during pregnancy is unsuit-able. A non-invasive method for repetitive assess-ment of renal hemodynamics is needed for use ininvestigations of the kidney in pregnancy. TheDoppler ultrasound technique is entirely non-invasive, simple and quick to carry out and pro-vides instant results. The development of duplexDoppler sonography has allowed non-invasivestudies of blood flow patterns in deep abdominaland pelvic vessels. The acquisition of the Dopplerinformation combined with color flow mappingensures accurate localization of the blood vesseland reliable biood flow velocity measurements. Renal artery blood flow velocity waveformshave been studied in normal and hypertensivepregnancies, but the results to date have been con-tradictory. During normal pregnancy the glomeru-lar filtration rate and renal blood flow increase by50% and 60-80%, respectively. There are oftenappreciable changes in kidney function inpreeclampsia, reflected in the decrement of renalblood flow and glomerular filtration rate. The his-tological abnormalities in the kidney in womenwith preeclampsia and eclampsia are quite welldefined and termed 'glomerular capillary endothe-liosis.' Thus, renal artery Doppler indices in normalpregnancy and in preeclampsia might be affectedconcomitantly with the known renal hemodynamicand morphological changes, and might be of use inrenal function examinations on a routine basis dur-ing pregnancy.Materials and Methods. Nonpregnant women andwomen with normal and hypertensive pregnancieswere studied by color Doppler ultrasonography,renal blood flow velocities being examined at thelevel of segmental arteries.Results and Conclusions. Color flow mappingcombined with the pulsed Doppler technique is areliable means of assessing renal blood flow veloc-ity as expressed in dimensionless indices. The mostsuitable vessels for examination were found to bethose in the middle portion of the kidney. The re-sults suggest that of all indices studied the pulsatil-ity index (Pl) might be more accurate for theevaluation of renal blood flow velocity. This studyclearly showed that repeated measurements shouldbe performed at least at the same level of the arte-rial branching in the kidney. Obtaining reliable Doppler indices required fiveor six cardiac cycles in nonpregnant women butonly three cardiac cycles in pregnant women. The findings demonstrated maternal heart rateto have no influence on renal artery Doppler indi-ces. There were no differences in Doppler indicesbetween the right and left kidney. Renal Doppler indices are significantly higherin pregnant than in nonpregnant women, and thereis no significant change in these indices throughoutnormal pregnancy. Renal artery Doppler indices are lower inwomen with preeclampsia, PIH and chronic hyper-tension than in normal pregnant women. The find-ings suggest that the mechanism of renal autoregu-lation might be altered in preeclampsia, leaving theglomeruli unprotected from increased blood pres-sure. These indices do not distinguish preeclampsiafrom other hypertensive disorders in pregnancy.Thus, renal artery Doppler velocimetry is of limitedvalue for the evaluation of pregnancies complicatedby hypertension. Despite similar central hemodynamic changesand plasma atrial natriuretic peptide (ANP) in-creases during volume expansion, renal vascularresistance, as estimated by renal artery Pl increasedonly in healthy pregnant women and not in patientswith PIH/preeclampsia. It seems that ANP is partlyresponsible for the renal hemodynamic changescaused by volume load, and that this response isaltered in preeclampsia. Renal artery PI was significantly increased inpreeclamptic women afler 60 minutes infusion ofANP at low doses. Whether such variables as bloodpressure and plasma volume status are determinantsof hemodynamic response to ANP remains to beelucidated. Gosling's model seems to be useful for the in-terpretation of PI in low resistance vascular beds,and might provide new information of kidneypathophysiology. Our results emphasize that renal Doppler indi-ces should be interpreted with caution when assess-ing renal blood flow in pregnant women, as otherhemodynamic factors might influence the results.Blood pressure should always be taken into ac-count.Key words: Atrial natriuretic factor; Cyclicguanosine monophosphate; Doppler ultrasound;Kidney; Modeling; Preeclampsia; Pregnancy; Preg-nancy induced hypertension; Pulsatility index; Re-nal artery; Renal blood flow; Repeatability.Stockholm 1966 ISBN 91-628-1931-

Both Acute and Chronic Placental Inflammation Are Overrepresented in Term Stillbirths: A Case-Control Study

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