Reference ranges for third-trimester maternal cardiovascular function parameters measured in normotensive pregnant women using a non-invasive cardiac output monitor: A study based on data from the prospective PEACH cohort study.

OBJECTIVE: We defined reference ranges for maternal cardiac output, systemic vascular resistance, and stroke volume measured in the third trimester of pregnancy using the Ultrasound Cardiac Output Monitor 1A. DESIGN: Based on data from the prospective PEACH (PreEclampsia, Angiogenesis, Cardiac dysfunction and Hypertension) cohort study. SETTING: Rigshospitalet and Hvidovre Hospital, Denmark. SAMPLE: Normotensive pregnant women aged 18-45 years with singleton pregnancies, enrolled in the PEACH study in 2016-2018. METHODS: We modelled cardiac output, systemic vascular resistance and stroke volume as a function of gestational age using multilevel linear models with fractional polynomials. MAIN OUTCOME MEASURES: Unconditional and conditional reference ranges for cardiovascular parameters measured in gestational weeks 28-40. RESULTS: Our study cohort included 405 healthy pregnant women who contributed 1210 cardiovascular function measurements for analysis. Maximum cardiac output and stroke volume values were measured in gestational weeks 30-32 and decreased over the third trimester, whereas systemic vascular resistance increased during the same period. We created reference ranges for eight combinations of maternal height, age and parity. We also created a simple calculator to allow for implementation of the reference ranges in clinical practice. CONCLUSIONS: Our reference ranges allow the use of a bedside ultrasound device to non-invasively assess cardiac function in pregnancy and identify women at risk of complications. The unconditional ranges allow clinicians to evaluate isolated measurements and identify women needing follow-up. The conditional ranges incorporate information from previous measurements and improve monitoring over time.

Time trends in preeclampsia and gestational diabetes in Denmark and Alberta, Canada, 2005-2018-A population-based cohort study.

INTRODUCTION: Preeclampsia and gestational diabetes mellitus share risk factors such as obesity and increased maternal age, which have become more prevalent in recent decades. We examined changes in the prevalence of preeclampsia and gestational diabetes between 2005 and 2018 in Denmark and Alberta, Canada, and investigated whether the observed trends can be explained by changes in maternal age, parity, multiple pregnancy, comorbidity, and body mass index (BMI) over time. MATERIAL AND METHODS: This study was a register-based cohort study conducted using data from the Danish National Health Registers and the provincial health registers of Alberta, Canada. We included in the study cohort all pregnancies in 2005-2018 resulting in live-born infants and used binomial regression to estimate mean annual increases in the prevalence of preeclampsia and gestational diabetes in the two populations across the study period, adjusted for maternal characteristics. RESULTS: The study cohorts included 846 127 (Denmark) and 706 728 (Alberta) pregnancies. The prevalence of preeclampsia increased over the study period in Denmark (2.5% to 2.9%) and Alberta (1.7% to 2.5%), with mean annual increases of 0.03 (95% confidence interval [CI] 0.02-0.04) and 0.06 (95% CI 0.05-0.07) percentage points, respectively. The prevalence of gestational diabetes also increased in Denmark (1.9% to 4.6%) and Alberta (3.9% to 9.2%), with average annual increases of 0.20 (95% CI 0.19-0.21) and 0.44 (95% CI 0.42-0.45) percentage points. Changes in the distributions of maternal age and BMI contributed to increases in the prevalence of both conditions but could not explain them entirely. CONCLUSIONS: The prevalence of both preeclampsia and gestational diabetes increased significantly from 2005 to 2018, which portends future increases in chronic disease rates among affected women. Increasing demand for long-term follow up and care will amplify the existing pressure on healthcare systems.

Cohort profile: The PreEclampsia, Angiogenesis, Cardiac dysfunction and Hypertension (PEACH) Study.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) remain a leading cause of maternal morbidity and mortality worldwide, with implications for maternal and neonatal well-being in the short term and for long-term maternal cardiovascular health. Although the mechanisms behind HDP remain incompletely understood, evidence suggests that preeclampsia in particular is a syndrome with more than one distinct subtype. OBJECTIVES: The PEACH (PreEclampsia, Angiogenesis, Cardiac dysfunction, Hypertension) Study was established to identify new HDP subtyping systems reflecting aetiology and prognosis and to find markers of later cardiovascular disease risk associated with preeclampsia. POPULATION: The PEACH Study recruited pregnant women referred to two Copenhagen-area hospitals with suspected preeclampsia (mean gestational age at enrolment: 36.7 weeks) and a group of frequency-matched pregnant women planning delivery at the same hospitals and healthy when enrolled mid-pregnancy. DESIGN: Prospective, longitudinal pregnancy cohort. METHODS: Participants underwent repeated third-trimester blood sample collection, longitudinal cardiac function assessments using the USCOM-1A during the third trimester and at 1 year postpartum and collection of placental samples immediately after delivery. Medical information was abstracted from medical records and hospital databases. PRELIMINARY RESULTS: During 2016-2018, we recruited 1149 pregnant women, of whom 1101 were followed to delivery. Among 691 women enrolled with suspected preeclampsia, 310 and 172 developed preeclampsia and gestational hypertension respectively. Among 410 women with healthy pregnancies when enrolled mid-pregnancy, 37 later developed hypertensive disorders of pregnancy. Of 1089 women still in the cohort 1 year postpartum, 578 (53.1%) participated in the follow-up assessment. CONCLUSIONS: The PEACH Study's rich data from women with and without HDP will enable us to identify new, clinically useful HDP subtypes to aid in decision-making regarding monitoring and treatment. Continued postpartum follow-up will help us develop algorithms to identify women at risk of persistent postpartum cardiac dysfunction and later cardiovascular disease after pregnancies complicated by HDP.

Rebozo and External Cephalic Version in breech presentation (RECEIVE): A randomised controlled study.

OBJECTIVE: To investigate if a hospital-initiated home-based rebozo intervention performed by the pregnant woman and her partner before external cephalic version (ECV) would increase the rate of cephalic presentations at birth. DESIGN: A multicentre randomised controlled trial. SETTING: Three university hospitals in Copenhagen, Denmark. POPULATION: Pregnant women with a breech or transverse presentation at 35 weeks or more of gestation eligible for ECV. METHODS: We compared rebozo before ECV with ECV alone. The randomisation was computer-generated in blocks and stratified by parity. The woman and her partner were instructed in the technique by a project midwife and performed the technique at home three times daily for 3-5 days before the scheduled ECV. Analyses were by intention-to-treat. MAIN OUTCOME MEASURE: The number of cephalic presentations at the time of birth. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: A total of 372 women were randomly assigned (1:1) to either rebozo intervention (n = 187) or control (n = 185). At birth, 95 (51%) in the intervention group versus 112 (62%) in the control group had a fetus in cephalic presentation (OR 0.61; 95% CI 0.40-0.95). No adverse events were observed in relation to the intervention. CONCLUSIONS: In breech or transverse presentation, home-based rebozo exercise before ECV lowered the overall rate of cephalic presentation at birth. TWEETABLE ABSTRACT: Home-based rebozo for breech presentation before external version reduces the rate of cephalic presentation at birth.

Differentiated timing of induction for women with intrahepatic cholestasis of pregnancy-A historical cohort study.

INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease characterized by pruritus and abnormal liver function tests and it has been associated with intrauterine fetal distress and stillbirth. We compared two guidelines of the management of ICP: one mandating induction at 38 weeks of gestation (Rigshospitalet and Hvidovre Hospital before 2012) and another separating ICP into mild and severe forms, and only women with severe ICP were recommended for induction at 38 weeks (Hvidovre Hospital after 2012). MATERIAL AND METHODS: We performed a historical cohort study at two Copenhagen Hospitals from 2004 to 2015. We included 62 937 women with singleton deliveries at Rigshospitalet and 71 015 at Hvidovre Hospital, of whom 971 women (1.5%) and 998 women (1.4%) were diagnosed with ICP at Rigshospitalet and Hvidovre Hospital, respectively. Data were retrieved from a local medical database. For the analysis of induction and comparison of obstetrical outcomes we only included pregnancies with an ICP diagnosis and excluded women with other medical conditions that could mandate induction. Main outcome measures were induction and cesarean section rates, asphyxia and stillbirth. RESULTS: We found no changes in the rate of spontaneous labor, cesarean section and induction over the years at Rigshospitalet (P = .17) and Hvidovre Hospital (P = .38). For women with intended vaginal delivery we found no change in the final mode of delivery over the years at Rigshospitalet (P = .28) and Hvidovre Hospital (P = .57). CONCLUSIONS: The two approaches to the management of mild ICP regarding the timing of induction are comparable. Women with mild ICP and their clinicians should be encouraged to engage in shared decision-making when discussing timing of induction.

Hypertensive disorders of pregnancy and subsequent risk of solid cancer--A nationwide cohort study.

Women with hypertensive disorders of pregnancy (HDP) have higher levels of antiangiogenic growth factors during pregnancy than women with normotensive pregnancies. Since angiogenesis is necessary for solid cancer growth and spread, we hypothesized that women with a history of HDP might have a reduced risk of solid cancers (cancers other than lymphomas, hematologic cancers and nonmelanoma skin cancers) later in life. In a register-based cohort study of 1.08 million women giving birth at least once between 1978 and 2011, we used Cox regression to estimate hazard ratios (HRs) comparing solid cancer rates for women with and without a history of HDP. In this cohort, 68,236 women (6.3%) had ≥1 pregnancy complicated by HDP and 42,236 women (3.9%) developed solid tumors during follow-up. A history of HDP was not associated with a clinically meaningful reduction in the overall rate of solid cancer (HR 0.96, 95% confidence interval 0.92-1.00), regardless of HDP severity or time since HDP, nor was there a general tendency toward reduced solid cancer rates across organ sites. A history of HDP was only significantly associated with decreased rates of breast and lung cancers and with increased rates of endometrial and urinary tract cancers. Overall, our results do not support the hypothesis that women with a history of HDP have a reduced overall risk of solid cancer due to a persistent post-HDP antiangiogenic state or an innate tendency toward antiangiogenesis. Observed associations with specific cancers may instead be due to other pregnancy-related mechanisms or to residual/unmeasured confounding.

Association Between Hypertensive Disorders of Pregnancy and Later Risk of Cardiomyopathy.

IMPORTANCE: Women with hypertensive disorders of pregnancy, preeclampsia in particular, have an increased risk of cardiomyopathy during the peripartum period. Whether hypertensive disorders of pregnancy are also associated with cardiomyopathy later in life is unknown. OBJECTIVE: To determine whether hypertensive disorders of pregnancy are associated with cardiomyopathy beyond the peripartum period. DESIGN, SETTING, AND PARTICIPANTS: Nationwide register-based cohort study using Cox regression to compare rates of cardiomyopathy in women with and without a history of hypertensive disorders of pregnancy in a cohort of 1,075,763 women with at least 1 pregnancy ending in live birth or stillbirth in Denmark, 1978-2012, with follow-up through December 31, 2012. EXPOSURES: A hypertensive disorder of pregnancy (severe or moderate preeclampsia or gestational hypertension) registered in the National Patient Register. MAIN OUTCOMES AND MEASURES: Cardiomyopathy more than 5 months after delivery (outside the peripartum period) up to 34 years 7 months. RESULT: The women in the primary cohort had 2,067,633 eligible pregnancies during the study period, 76,108 of which were complicated by a hypertensive disorder of pregnancy. During follow-up, 1577 women (mean age, 48.5 years at cardiomyopathy diagnosis; 2.6% with multiple pregnancies) developed cardiomyopathy. Compared with women with normotensive pregnancies (18,211,603 person-years of follow-up; n = 1408 cardiomyopathy events, 7.7/100,000 person-years [95% CI, 7.3-8.2]), women with a history of hypertensive disorders of pregnancy had significantly increased rates of cardiomyopathy (in 173,062 person-years of follow-up among women with severe preeclampsia, n = 27 cardiomyopathy events; 15.6/100,000 person-years [95% CI, 10.7-22.7]; adjusted hazard ratio [HR], 2.20 [95% CI, 1.50-3.23]; in 697,447 person-years of follow-up among women with moderate preeclampsia, n = 102 cardiomyopathy events; 14.6/100,000 person-years [95% CI, 12.0-17.8]; adjusted HR, 1.89 [95% CI, 1.55-2.23]; in 213,197 person-years of follow-up among women with gestational hypertension, n = 40 cardiomyopathy events; 17.3/100,000 person-years [95% CI, 12.7-23.6]; adjusted HR, 2.06 [95% CI, 1.50-2.82]). These increases persisted more than 5 years after the latest pregnancy. Mediation analyses suggested that only about 50% of the association was an indirect association through postpregnancy chronic hypertension. In this cohort, 11% of all cardiomyopathy events occurred in women with a history of hypertensive disorders of pregnancy. CONCLUSIONS AND RELEVANCE: Women with a history of hypertensive disorders of pregnancy, compared with women without such a history, had a small but statistically significant increased risk of cardiomyopathy more than 5 months after delivery. Further research is necessary to understand whether there is a causal mechanism behind this association.

Recurrence of hypertensive disorders of pregnancy: an individual patient data metaanalysis.

OBJECTIVE: We performed an individual participant data (IPD) metaanalysis to calculate the recurrence risk of hypertensive disorders of pregnancy (HDP) and recurrence of individual hypertensive syndromes. STUDY DESIGN: We performed an electronic literature search for cohort studies that reported on women experiencing HDP and who had a subsequent pregnancy. The principal investigators were contacted and informed of our study; we requested their original study data. The data were merged to form one combined database. The results will be presented as percentages with 95% confidence interval (CI) and odds ratios with 95% CI. RESULTS: Of 94 eligible cohort studies, we obtained IPD of 22 studies, including a total of 99,415 women. Pooled data of 64 studies that used published data (IPD where available) showed a recurrence rate of 18.1% (n=152,213; 95% CI, 17.9-18.3%). In the 22 studies that are included in our IPD, the recurrence rate of a HDP was 20.7% (95% CI, 20.4-20.9%). Recurrence manifested as preeclampsia in 13.8% of the studies (95% CI,13.6-14.1%), gestational hypertension in 8.6% of the studies (95% CI, 8.4-8.8%) and hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome in 0.2% of the studies (95% CI, 0.16-0.25%). The delivery of a small-for-gestational-age child accompanied the recurrent HDP in 3.4% of the studies (95% CI, 3.2-3.6%). Concomitant HELLP syndrome or delivery of a small-for-gestational-age child increased the risk of recurrence of HDP. Recurrence increased with decreasing gestational age at delivery in the index pregnancy. If the HDP recurred, in general it was milder, regarding maximum diastolic blood pressure, proteinuria, the use of oral antihypertensive and anticonvulsive medication, the delivery of a small-for-gestational-age child, premature delivery, and perinatal death. Normotensive women experienced chronic hypertension after pregnancy more often after experiencing recurrence (odds ratio, 3.7; 95% CI, 2.3-6.1). CONCLUSION: Among women that experience hypertension in pregnancy, the recurrence rate in a next pregnancy is relatively low, and the course of disease is milder for most women with recurrent disease. These reassuring data should be used for shared decision-making in women who consider a new pregnancy after a pregnancy that was complicated by hypertension.

Angiogenic biomarkers in pregnancy: defining maternal and fetal health.

We review diagnostic and predictive roles of the angiogenic proteins placental growth factor, soluble fms-like tyrosine kinase 1, and soluble endoglin in preeclampsia, and their association with future cardiovascular disease, diabetes, and breast cancer. Specific patterns of these proteins represent preeclamptic prediction markers and combined with maternal and clinical characteristics, the predictive values increase. Women experiencing preeclampsia have increased risks of developing cardiovascular diseases and diabetes, and a decreased risk of breast cancer. High placental growth factor concentrations have, in elderly patients, been shown to predict cardiovascular events. Diabetes is also a risk factor for future cardiovascular disease. Diabetic vascular complications are associated with increased soluble endoglin concentrations, and vascular endothelial growth factor concentrations are correlated to HbA1c and fasting glucose. Hence dysregulation in angiogenic proteins may link preeclampsia and cardiovascular diseases, targeting women who could in future benefit from prophylactic programs to possibly prevent, delay or reduce cardiovascular disease.

Fetal growth and later maternal death, cardiovascular disease and diabetes.

OBJECTIVES: Low birthweight of the offspring has been associated with increased risk of early death and ischemic heart disease in the mother. However, other measurements of fetal growth than the basic birthweight are more accurate. We investigated the relation between the standardized birthweight by gestational age and gender and the ponderal index and the mother's subsequent mortality and cardiovascular morbidity. DESIGN: Registry-based retrospective cohort study. SETTING: Women with a first singleton delivery in Denmark from 1978 to 2007. POPULATION: 782 287 women followed for 14.6 years yielding 11 600 945 person-years. METHODS: Cox proportional hazard models. MAIN OUTCOME MEASURES: The primary exposures were variation in the standardized birthweight and ponderal index. The endpoints were subsequent maternal death, hypertension, ischemic heart disease, stroke, thrombosis, and diabetes mellitus. RESULTS: The risk-profile for the standardized birthweight and subsequent maternal death had a nadir between -0.5 and -1 SD (HR 0.91; 95%CI 0.83-1.00) and increased with decreasing fetal growth peaking at <-3 SD (HR 2.75; 95%CI 2.37-3.19) compared to the median. The risk-profile for subsequent diabetes mellitus by standardized ponderal index had a nadir between +0.5 to +1 SD (HR 0.82; 95%CI 0.76-0.89) rising with increasing fetal growth and peaking at >+3 SD (HR 17.8; 95%CI 15.0-21.0). The risk-profiles for standardized ponderal index paralleled those for birthweight, but with smaller risk estimates. Adjusting for other pregnancy complications diminished the estimates. CONCLUSION: The fetal growth is a marker of subsequent risk for premature death, cardiovascular disease, and diabetes mellitus in the mother.

Vascular associated gene variants in patients with preeclampsia: results from the Danish National Birth Cohort.

OBJECTIVE: Preeclampsia has been linked to subsequent vascular disease with many shared predisposing factors. We investigated the association between severe preeclampsia, and its subtypes, and specific vascular-related polymorphisms. DESIGN: The study was a retrospective nested case-cohort design. SETTING: Pregnant Danish women participating in the Danish National Birth Cohort. Population. 263 cases of severe preeclampsia and 1851 random controls were selected from the Danish National Birth Cohort. METHODS: We validated all cases of severe preeclampsia and genotyped for 108 single nucleotide polymorphisms (SNPs) that were selected based on previous publications on the association with vascular disease. Logistic models were used for statistical analyses. MAIN OUTCOME MEASURES: Maternal polymorphisms in genomic models. RESULTS: We found 17 of 108 SNPs associated with severe preeclampsia (p < 0.05). Women homozygous for the rs1799983 in NOS3 were 1.6-fold [95% confidence interval (CI) 1.0-2.4] more likely to develop severe preeclampsia. Women homozygous for the rs1010 SNP in VAMP8 were twofold (95%CI 1.1-3.5) more likely to deliver preterm when preeclampsia was present. Women homozygous for the rs10811661 SNP were 2.1-fold (95%CI 1.1-3.9) more likely to develop severe preeclampsia and 3.7-fold (95%CI 1.1-12.4) more likely to deliver a small-for-gestational age child when preeclampsia was present. All associations are available as Supporting Information. CONCLUSION: We found several vascular-associated SNPs linked to severe preeclampsia; however, most of these associations are probably by pure chance, which warrants replication and further translational research. To date, no specific SNP has yet proven valuable in a clinical setting in predicting preeclampsia.

Mortality of mothers from cardiovascular and non-cardiovascular causes following pregnancy complications in first delivery.

The combined effects of preterm delivery, small-for-gestational-age offspring, hypertensive disorders of pregnancy, placental abruption and stillbirth on early maternal death from cardiovascular causes have not previously been described in a large cohort. We investigated the effects of pregnancy complications on early maternal death in a registry-based retrospective cohort study of 782 287 women with a first singleton delivery in Denmark 1978-2007, followed for a median of 14.8 years (range 0.25-30.2) accruing 11.6 million person-years. We employed Cox proportional hazard models of early death from cardiovascular and non-cardiovascular causes following preterm delivery, small-for-gestational-age offspring and hypertensive disorders of pregnancy. We found that preterm delivery and small-for-gestational-age were both associated with subsequent death of mothers from cardiovascular and non-cardiovascular causes. Severe pre-eclampsia was associated with death from cardiovascular causes only. There was a less than additive effect on cardiovascular mortality hazard ratios with increasing number of pregnancy complications: preterm delivery 1.90 [95% confidence intervals 1.49, 2.43]; preterm delivery and small-for-gestational-age offspring 3.30 [2.25, 4.84]; preterm delivery, small-for-gestational-age offspring and pre-eclampsia 3.85 [2.07, 7.19]. Thus, we conclude that, separately and combined, preterm delivery and small-for-gestational-age are strong markers of early maternal death from both cardiovascular and non-cardiovascular causes, while hypertensive disorders of pregnancy are markers of early death of mothers from cardiovascular causes.

Recurring complications in second pregnancy.

OBJECTIVE: To clarify the obstetric consequences in a second pregnancy after a first singleton pregnancy complicated by spontaneous preterm delivery or preeclampsia and stratified by the variation in fetal growth. METHODS: In a registry-based cohort study, we identified women having a first and second singleton delivery in Denmark from 1978 to 2007 (n=536,419). The exposures and endpoints were preterm delivery, preeclampsia, fetal growth, placental abruption, and stillbirth after 20 weeks of gestation. We used chi and t test to compare differences between incidences on first and second pregnancies. RESULTS: Compared with a spontaneous first delivery at term, a delivery between 32 and 36 weeks of gestation increased the risk of preterm delivery in the second pregnancy from 2.7% to 14.7% (odds ratio [OR] 6.12, 95% confidence interval [CI] 5.84-6.42) and the risk of preeclampsia from 1.1% to 1.8% (OR 1.60, 95% CI 1.41-1.81); a delivery before 28 weeks increased the risk of a second preterm delivery to 26.0% (OR 13.1, 95% CI 10.8-15.9) and a second pregnancy with preeclampsia to 3.2% (OR 2.96, 95% CI 1.80-4.88). A first delivery in preeclamptic women between 32 and 36 weeks, compared with delivery after 37 weeks, increased the risk of preeclampsia in a second pregnancy from 14.1% to 25.3% (OR 2.08, 95% CI 1.87-2.31) and a small for gestational age infant from 3.1% to 9.6% (OR 2.82, 95% CI 2.38-3.35). Compared with the mean, fetal growth 2 to 3 standard deviations below mean in the first pregnancy increased the risk of preeclampsia from 1.1% to 1.8% (OR 1.62, 95% CI 1.34-1.96) in the second pregnancy. CONCLUSION: Spontaneous preterm delivery, preeclampsia, and fetal growth deviation tend to recur and predispose to each other in a second pregnancy. Severe complications further increase these risks. LEVEL OF EVIDENCE: II.

Hypertensive disorders of pregnancy and peripartum cardiomyopathy: A nationwide cohort study.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a serious cardiac disorder occurring late in pregnancy or early in the postpartum period. We examined associations between hypertensive disorders of pregnancy (HDP: preeclampsia and gestational hypertension) and PPCM, accounting for other pregnancy-related risk factors for PPCM. METHODS: Using nationwide Danish register data, we constructed a cohort of all women with ≥1 live birth or stillbirth in Denmark between 1978 and 2012. Using log-linear binomial regression and generalized estimating equations, we estimated risk ratios (RRs) for PPCM associated with HDP of varying severity. RESULTS: In a cohort of 1,088,063 women with 2,078,822 eligible pregnancies, 126 women developed PPCM (39 in connection with an HDP-complicated pregnancy). The risks of PPCM were significantly higher in women with HDP-complicated pregnancies than in women with normotensive pregnancies (severe preeclampsia, RR 21.2, 95% confidence interval [CI] 12.0-37.4; moderate preeclampsia, RR 10.2, 95% CI 6.18-16.9; gestational hypertension, RR 5.16, 95% CI 2.11-12.6). The RRs for moderate preeclampsia and gestational hypertension were not significantly different from one another (p = 0.18); the RR for severe preeclampsia was significantly different from the RR for moderate preeclampsia and gestational hypertension combined (p = 0.02). CONCLUSIONS: Although 70% of PPCM occurred in women with normotensive pregnancies, HDPs were associated with substantial increases in PPCM risk that depended on HDP severity. The heart's capacity to adapt to a normal pregnancy may be exceeded in some women already susceptible to cardiac insult, contributing to PPCM. HDPs, severe preeclampsia in particular, probably represent an additional cardiac stressor during pregnancy.

Treatment of deep venous thrombosis in pregnant women.

The recommended dosage of tinzaparin in the treatment of thromboembolism during pregnancy is 175 IU/kg/day, as for non-pregnant subjects. In clinical practice, we have experienced a need for a higher dosage, especially in the initial phase of the treatment of deep vein thrombosis, based on four-hour post-dose measurements of anti-Xa activity. Twenty-two pregnant patients with a confirmed deep venous thrombosis were treated with tinzaparin either in a once- or twice-daily regimen. Four-hour post-dosage plasma anti-Xa activity was measured in 357 sequential blood samples during treatment. An higher dosage than recommended, was required to maintain anti-Xa activity in the target range. We suggest that the starting dosage should be 250 IU/kg/day in a twice-daily regimen, and that the dose in the initial phase be adjusted by daily monitoring of anti-Xa.

Population-based investigations to study the association of cardiovascular polymorphisms and adverse pregnancy outcome.

Adverse pregnancy outcome refers to placenta-mediated complications that may share a common etiopathogenesis in some cases. Unraveling associations between prothrombotic genetic predispositions and these pregnancy disorders, namely recurrent fetal loss, stillbirth, severe preeclampsia, intrauterine growth restriction, and placental abruption, requires rigorous epidemiological studies involving large cohorts of patients with sufficient numbers of the adverse pregnancy outcomes in question. Such is the case with the Denmark National Birth Cohort, which was initiated in 1996 and followed pregnant women giving birth from the years 1996 to 2002. In addition, national registers exist which can be linked together. Two studies have been initiated. One is a retrospective cohort study concerning primiparous women, with singleton pregnancy and with no identifiable congenital malformation. The purpose of this study is to determine the long-term cardiovascular risk of women whose pregnancies were complicated by adverse pregnancy outcome. Preliminary evidence suggests that the presence of an adverse pregnancy outcome augments the cardiovascular disease risk by an odds ratio of 1.21 (P < 0.001). The second study focuses on pro-thrombotic and cardiovascular genetic polymorphisms in a nested-case control study comparing pregnancies with and without an adverse pregnancy outcome in the index pregnancy. This study will be adequately powered to determine the relationship between adverse pregnancy outcome and pro-thrombotic and cardiovascular genetic polymorphisms. These studies are urgently needed to accurately assess the linkage between family history, presence of adverse pregnancy outcome, and long-term cardiovascular risk.

Self-monitoring of blood pressure during pregnancy: an observational study in the obstetrical waiting room.

OBJECTIVE: The aim of this study was to assess the feasibility of self-monitoring of blood pressure with a semiautomatic device in pregnant women. PARTICIPANTS AND METHODS: Women attending routine obstetrical ultrasound scanning were invited to participate. The hospital staff initially demonstrated and instructed each participant in correct measurement and then took three measurements on both arms. The participant then repeated the measurements and filled an evaluation questionnaire. We used a validated semiautomatic device for all measurements. Mean values were calculated for systolic, diastolic and mean arterial blood pressure (MAP) and were compared using the paired sample t-test. Mean values and differences of systolic and diastolic pressure were plotted in Bland-Altman plots to test the agreement of the measurements. Finally, a mean evaluation score was calculated. RESULTS: One hundred pregnant women were included in the study. Mean values of systolic, diastolic and MAP were 110.6, 69.7 and 83.3 mmHg, respectively, as assessed by the hospital staff. The corresponding self-measurements were 111.4, 70.2 and 83.9 mmHg, respectively. Mean differences between hospital and self-measurements were 0.79 mmHg for systolic [P=0.052, 95% confidence interval (CI)=-0.008 to 1.58], 0.49 mmHg for diastolic (P=0.056, 95% CI=-0.01 to 0.99) and 0.59 mmHg for MAP (P=0.019, 95% CI=0.099-1.08). The mean evaluation score was 9.2 of 10. CONCLUSION: Differences between hospital staff and self-measurements in systolic, diastolic and MAP are within acceptable international standards. The semiautomatic device Microlife-VSA is well suited for self-measurement; however, safety studies on the use of home measurements in hypertensive pregnancies are still warranted.

Time from pre-eclampsia diagnosis to delivery affects future health prospects of children.

Background and objectives: Pre-eclampsia often has detrimental health effects for pregnant women and their fetuses, but whether exposure in the womb has long-term health-consequences for children as they grow up remains poorly understood. We assessed overall morbidity of children following exposure to either mild or severe pre-eclampsia up to 30 years after birth and related disease risks to duration of exposure, i.e. the time from diagnosis to delivery. Methodology: We did a registry-based retrospective cohort study in Denmark covering the years 1979-2009, using the separate diagnoses of mild and severe pre-eclampsia and the duration of exposure as predictor variables for specific and overall risks of later disease. We analysed 3 537 525 diagnoses for 14 disease groups, accumulated by 758 524 singleton children, after subdividing deliveries in six gestational age categories, partialing out effects of eight potentially confounding factors. Results: Exposure to mild pre-eclampsia appeared to have consistent negative effects on health later in life, although only a few specific disease cases remained significant after corrections for multiple testing. Morbidity risks associated with mild pre-eclampsia were of similar magnitude as those associated with severe pre-eclampsia. Apart from this overall trend in number of diagnoses incurred across disease groups, hazard ratios for several disorders also increased with the duration of exposure, including disorders related to the metabolic syndrome. Conclusions and implications: Maternal pre-eclampsia has lasting effects on offspring health and differences between exposure to severe and mild pre-eclampsia appear to be less than previously assumed. Our results suggest that it would be prudent to include the long-term health prospects of children in the complex clinical management of mild pre-eclampsia.

Risk of post-pregnancy hypertension in women with a history of hypertensive disorders of pregnancy: nationwide cohort study.

Objectives To determine how soon after delivery the risk of post-pregnancy hypertension increases in women with hypertensive disorders of pregnancy and how the risk evolves over time.Design Nationwide register based cohort study.Setting Denmark.Populations 482 972 primiparous women with a first live birth or stillbirth between 1995 and 2012 (cumulative incidence analyses), and 1 025 118 women with at least one live birth or stillbirth between 1978 and 2012 (Cox regression analyses).Main outcome measures 10 year cumulative incidences of post-pregnancy hypertension requiring treatment with prescription drugs, and hazard ratios estimated using Cox regression.Results Of women with a hypertensive disorder of pregnancy in a first pregnancy in their 20s, 14% developed hypertension in the first decade post partum, compared with 4% of women with normotensive first pregnancies in their 20s. The corresponding percentages for women with a first pregnancy in their 40s were 32% and 11%, respectively. In the year after delivery, women with a hypertensive disorder of pregnancy had 12-fold to 25-fold higher rates of hypertension than did women with a normotensive pregnancy. Rates in women with a hypertensive disorder of pregnancy were threefold to 10-fold higher 1-10 years post partum and remained twice as high even 20 or more years later.Conclusions The risk of hypertension associated with hypertensive disorders of pregnancy is high immediately after an affected pregnancy and persists for more than 20 years. Up to one third of women with a hypertensive disorder of pregnancy may develop hypertension within a decade of an affected pregnancy, indicating that cardiovascular disease prevention in these women should include blood pressure monitoring initiated soon after pregnancy.

[Systemic lupus erythematosus and pregnancy].

Systemic lupus erythematosus (SLE) is a complex autoimmune disease which most often affects women of childbearing age. Pregnancy is therefore an important issue for the patient and the responsible physician. Pregnancy outcomes in women with SLE has improved significantly over the latest decades, and current research initiatives aim towards further improvement. Pregnant women with SLE are still considered being at various levels of risk. In order to achieve the best possible outcomes for mother and child, joint care in specialised multidisciplinary teams including rheumatologists and obstetricians is recommended.