Maternal lipid levels in early pregnancy as a predictor of childhood lipid levels: a prospective cohort study.

BACKGROUND: Maternal lipid levels in early pregnancy are associated with maternal health and foetal growth. It is however unclear if maternal lipids in early pregnancy can be used to predict childhood lipid levels. The aim of this study is to assess the association between maternal and offspring childhood lipid levels, and to investigate the influence of maternal BMI and diet on these associations. METHODS: This study included 2692 women participating in the Generation R study, an ongoing population-based prospective cohort study from early life onwards. Women with an expected delivery date between 2002 and 2006 living in Rotterdam, the Netherlands were included. Total cholesterol, triglycerides and high-density lipoprotein cholesterol (HDL-c) were measured in early pregnancy (median 13.2 weeks [90% range 10.6; 17.1]). Low-density lipoprotein cholesterol (LDL-c), remnant cholesterol and non-HDL-c were calculated. Corresponding lipid measurements were determined in 2692 children at the age of 6 (median 6.0 years [90% range 5.7; 7.5]) and 1673 children 10 years (median 9.7 years [90% range 9.5; 10.3]). Multivariate linear regression analysis was used to examine the association between maternal lipid levels in early pregnancy and the corresponding childhood lipid measurements at the ages of 6 and 10 years while adjusting for confounders. RESULTS: Maternal lipid levels in early pregnancy are positively associated with corresponding childhood lipid levels 6 and 10 years after pregnancy, independent of maternal body mass index and diet. CONCLUSIONS: Maternal lipid levels in early pregnancy may provide an insight to the lipid profile of children years later. Gestational lipid levels may therefore be used as an early predictor of children's long-term health. Monitoring of these gestational lipid levels may give a window-of-opportunity to start early interventions to decrease offspring's lipid levels and possibly diminish their cardiovascular risk later in life. Future studies are warranted to investigate the genetic contribution on maternal lipid levels in pregnancy and lipid levels of their offspring years later.

Gestational lipid profile as an early marker of metabolic syndrome in later life: a population-based prospective cohort study.

BACKGROUND: In pregnancy lipid levels increase with gestation resembling an atherogenic lipid profile. Currently it is unclear whether gestational lipid levels are associated with an adverse cardiovascular risk profile later in life. The aim of this study is to assess the association between gestational lipid levels and lipid levels and prevalence of the metabolic syndrome (MS) six years after pregnancy. METHODS: In plasma of 3510 women from the Generation R Study; a prospective population-based cohort, we measured lipid levels (total cholesterol, triglycerides and high-density lipoprotein cholesterol [HDL-c]), and low-density lipoprotein cholesterol (LDL-c), remnant cholesterol and non-HDL-c were calculated in early pregnancy (median 13.2 weeks, 90% range [10.5 to 17.1]) and six years after pregnancy (median 6.5 years, 90% range [6.2 to 7.8]). MS was assessed six years after pregnancy according to the NCEP/ATP3 criteria. We also examined the influence of pregnancy complications on these associations. RESULTS: Gestational lipid levels were positively associated with corresponding lipid levels six years after pregnancy, independent of pregnancy complications. Six years after pregnancy the prevalence of MS was 10.0%; the prevalence was higher for women with a previous placental syndrome (13.5%). Gestational triglycerides and remnant cholesterol in the highest quartile and HDL-c in the lowest quartile were associated with the highest risk for future MS, independent of smoking and body mass index. CONCLUSIONS: Gestational lipid levels provide an insight in the future cardiovascular risk profile of women in later life. Monitoring and lifestyle intervention could be indicated in women with an unfavorable gestational lipid profile to optimize timely cardiovascular risk prevention.

Early Onset of Coronary Artery Calcification in Women With Previous Preeclampsia.

BACKGROUND: Preeclampsia, coronary artery calcification (CAC), and atherosclerotic plaque are risk factors for the development of cardiovascular disease. We determined at what age CAC becomes apparent on coronary computed tomography after preeclampsia and to what extent modifiable cardiovascular risk factors were associated. METHODS: We measured cardiovascular risk factors, CAC by coronary computed tomography, and coronary plaque by coronary computed tomography angiography in 258 previously preeclamptic women aged 40-63. Results were compared to 644 age- and ethnicity-equivalent women from the Framingham Heart Study with previous normotensive pregnancies. RESULTS: Any CAC was more prevalent after preeclampsia than after a normotensive pregnancy (20% versus 13%). However, this difference was greatest and statistically significant only in women ages 45 to 50 (23% versus 10%). The degree of CAC advanced 4× faster between the ages of 40 to 45 and ages 45 to 50 in women with a history of preeclampsia (odds ratio, 4.3 [95% CI, 1.5-12.2] versus odds ratio, 1.2 [95% CI, 0.6-2.3]). Women with a preeclampsia history maintained greater advancement of CAC with age into their early 60s, although this difference declined after the perimenopausal years. Women with a previous normotensive pregnancy were 4.9 years (95% CI, 1.8-8.0) older when they had similar CAC scores as previously preeclamptic women. These observations were not explained by the greater prevalence of cardiovascular disease risk factors, and the higher Framingham Risk Scores also observed in women with a history of preeclampsia. CONCLUSIONS: Previously preeclamptic women have more modifiable cardiovascular risk factors and develop CAC ≈5 years earlier from the age of 45 years onwards compared to women with normotensive pregnancies. Therefore, women who experienced preeclampsia might benefit from regular cardiovascular screening and intervention before this age. Registration: URL: https://www.trialregister.nl/trial/5406; Unique identifier: NTR5531.

Maternal lipid profile in early pregnancy is associated with foetal growth and the risk of a child born large-for-gestational age: a population-based prospective cohort study : Maternal lipid profile in early pregnancy and foetal growth.

BACKGROUND: Lipids such as cholesterol and triglycerides play an important role in both maternal and foetal energy metabolism. Little is known about maternal lipid levels in pregnancy and their effect on foetal growth. The aim of this study was to assess maternal lipid levels, foetal growth and the risk of small-for-gestational age (SGA) and large-for-gestational age (LGA). METHODS: We included 5702 women from the Generation R Study, a prospective population-based cohort. Maternal lipid levels (total cholesterol, triglycerides and high-density lipoprotein cholesterol [HDL-c]) were measured in early pregnancy (median 13.4 weeks, 90% range [10.5 to 17.2]). Low-density lipoprotein cholesterol (LDL-c), remnant cholesterol and non-HDL-c were calculated. Foetal growth was measured repeatedly by ultrasound. Information on birth anthropometrics was retrieved from medical records. A birth weight below the 10th percentile was defined as SGA and above the 90th percentile as LGA. RESULTS: Maternal triglyceride and remnant cholesterol levels were associated with increased foetal head circumference and abdominal circumference growth rates. Triglycerides and remnant cholesterol were positively associated with the risk of LGA (odds ratio [OR] 1.11, 95% confidence interval [CI] [1.01 to 1.22] and OR 1.11, 95% CI [1.01 to 1.23], respectively). These associations were independent of maternal pre-pregnancy body mass index, but not maternal glucose levels. We observed no association between maternal lipids in early pregnancy and SGA. CONCLUSIONS: Our study suggests a novel association of early pregnancy triglyceride and remnant cholesterol levels with foetal growth, patterns of foetal growth and the risk of LGA. Future studies are warranted to explore clinical implication possibilities.

Fetal sex and maternal pregnancy outcomes: a systematic review and meta-analysis.

BACKGROUND: Since the placenta also has a sex, fetal sex-specific differences in the occurrence of placenta-mediated complications could exist. OBJECTIVE: To determine the association of fetal sex with multiple maternal pregnancy complications. SEARCH STRATEGY: Six electronic databases Ovid MEDLINE, EMBASE, Cochrane Central, Web-of-Science, PubMed, and Google Scholar were systematically searched to identify eligible studies. Reference lists of the included studies and contact with experts were also used for identification of studies. SELECTION CRITERIA: Observational studies that assessed fetal sex and the presence of maternal pregnancy complications within singleton pregnancies. DATA COLLECTION AND ANALYSES: Data were extracted by 2 independent reviewers using a predesigned data collection form. MAIN RESULTS: From 6522 original references, 74 studies were selected, including over 12,5 million women. Male fetal sex was associated with term pre-eclampsia (pooled OR 1.07 [95%CI 1.06 to 1.09]) and gestational diabetes (pooled OR 1.04 [1.02 to 1.07]). All other pregnancy complications (i.e., gestational hypertension, total pre-eclampsia, eclampsia, placental abruption, and post-partum hemorrhage) tended to be associated with male fetal sex, except for preterm pre-eclampsia, which was more associated with female fetal sex. Overall quality of the included studies was good. Between-study heterogeneity was high due to differences in study population and outcome definition. CONCLUSION: This meta-analysis suggests that the occurrence of pregnancy complications differ according to fetal sex with a higher cardiovascular and metabolic load for the mother in the presence of a male fetus. FUNDING: None.

Cardiovascular health and vascular age after severe preeclampsia: A cohort study.

BACKGROUND AND AIMS: Severe preeclampsia increases lifetime-risk for cardiovascular disease (CVD). It remains unclear when this risk translates to subclinical atherosclerosis and whether this is related to cardiovascular health (CVH) after pregnancy. Our aims were (1) to determine CVH after severe preeclampsia, (2) to relate CVH to carotid intima-media thickness (CIMT), as a marker of subclinical atherosclerosis and (3) to relate CVH to chronological and vascular age. METHODS: A prospective cohort study was performed in women with previous severe pre-eclampsia. CVH, proposed by the American Heart Association, was assessed one year after pregnancy. The CVH score (range 0-14) includes seven metrics (blood pressure, total-cholesterol, glucose, smoking, physical activity, diet and body mass index [BMI]), each weighted as poor (0), intermediate (1) or ideal (2). Vascular age was determined by CIMT. We related CVH to delta age (chronological age - vascular age). RESULTS: In 244 women, the median CVH score was 10 (90% range 7.0, 13.0). Low CVH (<10) was associated with a larger CIMT than high CVH (≥12) (median 626.3 µm vs. 567.0 µm, respectively). Higher CVH was also associated with a lower vascular age (-2.0 years, 95%CI -3.3, -0.60). Women with low CVH had a larger delta age (22.5 years [90% range -3.9, 49.6) than women with high CVH (16.5 years [90% range -11.9, 43.3). CONCLUSIONS: CVH is inversely related to subclinical atherosclerosis and to vascular age one year after severe preeclampsia. Especially low CVH is associated with a large difference between chronological age and vascular age. CVH counseling might provide the opportunity for timely cardiovascular prevention.

Early Pregnancy Cardiovascular Health and Subclinical Atherosclerosis.

Background Assessing and optimizing cardiovascular health (CVH) early in life, such as in pregnancy, could lead to a longer lifetime spent in better CVH and reduce the risk of cardiovascular disease. This might especially benefit women with a hypertensive disorder of pregnancy (HDP) who are more likely to develop atherosclerosis and cardiovascular disease. We hypothesized that CVH in pregnancy is related to later life CVH and carotid intima-media thickness (CIMT), and that these associations differ between women with a normotensive pregnancy and women with an HDP. Methods and Results This study was conducted within the prospective population-based Generation R Study. CVH in pregnancy was based on 5 metrics (blood pressure, total-cholesterol, glucose, smoking, and body mass index). Postpartum CVH additionally included physical activity and diet scores, according to the American Heart Association classification. Postpartum CVH and CIMT were measured 10 years after pregnancy. Results were analyzed for women with a normotensive pregnancy and those with an HDP. Women with a normotensive pregnancy (n=1786) and women with an HDP (n=138) were evaluated from early pregnancy until 10 years postpartum. Better CVH in early pregnancy was associated with a smaller CIMT and better postpartum CVH in all women, especially in those with an HDP (CIMT: -9.82 µm [95% CI: -17.98, -1.67]). Conclusions Already in pregnancy, better CVH is associated with a smaller CIMT and better CVH 10 years postpartum, especially in women with an HDP. As pregnancy is an incentive for women to improve lifestyle, assessing CVH in pregnancy might help improve postpartum CVH and reduce cardiovascular disease risk.

Future risk of cardiovascular disease risk factors and events in women after a hypertensive disorder of pregnancy.

Hypertensive disorders of pregnancy (HDP), such as gestational hypertension and pre-eclampsia, affect up to 10% of all pregnancies. These women have on average a twofold higher risk to develop cardiovascular disease (CVD) later in life as compared with women with normotensive pregnancies. This increased risk might result from an underlying predisposition to CVD, HDP itself or a combination of both. After pregnancy women with HDP show an increased risk of classical cardiovascular risk factors including chronic hypertension, renal dysfunction, dyslipidemia, diabetes and subclinical atherosclerosis. The prevalence and onset of cardiovascular risk factors depends on the severity of the HDP and the coexistence of other pregnancy complications. At present, guidelines addressing postpartum cardiovascular risk assessment for women with HDP show a wide variation in their recommendations. This makes cardiovascular follow-up of women with a previous HDP confusing and non-coherent. Some guidelines advise to initiate cardiovascular follow-up (blood pressure, weight and lifestyle assessment) 6-8 weeks after pregnancy, whereas others recommend to start 6-12 months after pregnancy. Concurrent blood pressure monitoring, lipid and glucose assessment is recommended to be repeated annually to every 5 years until the age of 50 years when women will qualify for cardiovascular risk assessment according to all international cardiovascular prevention guidelines.

Coronary artery calcification in middle-aged women with premature ovarian insufficiency.

OBJECTIVE: Women with premature ovarian insufficiency (POI) enter menopause before age 40. Early menopause was associated with increased risk for coronary artery disease (CAD), death from cardiovascular disease and all-cause mortality. We compared the prevalence of CAD between middle-aged women on average 10 years following the initial POI diagnosis, with a population-based cohort. DESIGN: Cross-sectional case-control study. PARTICIPANTS: Women from two Dutch University Medical Centers above 45 years of age previously diagnosed with POI (n = 98) were selected and compared with age- and race-matched controls from the Multi-Ethnic Study of Atherosclerosis (MESA). MEASUREMENTS: The primary outcome was detectable coronary artery calcium (CAC) determined by coronary computed tomography (CCT). RESULTS: Women with POI had significantly higher blood pressure, cholesterol and glucose, despite lower BMI compared to controls. Similar proportions of detectable CAC (CAC score >0 Agatston Units) were observed in women with POI and controls (POI n = 16 (16%), controls n = 52 (18%), P = 0.40 and Padj  = 0.93). In women with POI separately, we were not able to identify associations between CVD risk factors and CAC. The following CVD risk factors in controls were positively associated with CAC: age, diabetes mellitus, hypertension and LDL cholesterol. HRT use was negatively associated with CAC in controls. CONCLUSIONS: The presence of CAC did not differ significantly in women with POI around 50 years of age, compared to an age- and race-matched control group. We observe no increased calcified coronary disease in POI patients, despite the presence of unfavourable cardiovascular risk factors in these women.

Is maternal lipid profile in early pregnancy associated with pregnancy complications and blood pressure in pregnancy and long term postpartum?

BACKGROUND: An atherogenic lipid profile is a risk factor for the initiation and progression of atherosclerosis. This ultimately leads to cardiovascular disease. Women with a history of hypertensive disorders of pregnancy are at increased risk of sustained hypertension and cardiovascular disease later in life. Currently it is unclear whether dyslipidemia during pregnancy contributes to these risks. OBJECTIVE: The objective of the study was to determine the associations between early pregnancy maternal lipid profile, hypertensive disorders of pregnancy, and blood pressure during and years after pregnancy. STUDY DESIGN: We included 5690 women from the Generation R Study, an ongoing population-based prospective birth cohort. Two hundred eighteen women (3.8%) developed gestational hypertension and 139 (2.4%) preeclampsia. A maternal lipid profile consisting of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, remnant cholesterol, and non-high-density lipoprotein cholesterol was determined in early pregnancy (median, 13.4 weeks of gestation). Systolic and diastolic blood pressures were measured in early, mid-, and late pregnancy and 6 and 9 years after pregnancy. RESULTS: Triglycerides and remnant cholesterol in early pregnancy were positively associated with preeclampsia. Maternal lipid levels in early pregnancy were not associated with gestational hypertension. Total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and especially triglycerides and remnant cholesterol were positively associated with blood pressure in pregnancy and 6 and 9 years after pregnancy. Triglycerides and remnant cholesterol are positively associated with sustained hypertension 6 and 9 years after pregnancy. CONCLUSION: An atherogenic lipid profile in early pregnancy reflecting impaired triglyceride-rich lipoprotein metabolism is independently associated with preeclampsia and blood pressure throughout pregnancy but also with sustained hypertension long term postpartum. Lipid levels in early pregnancy may help to identify women at risk for future hypertension and perhaps also women at risk for future cardiovascular disease.

Placental Growth Factor as an Indicator of Maternal Cardiovascular Risk After Pregnancy.

BACKGROUND: Angiogenic placental growth factor (PlGF) concentrations rise during pregnancy, peaking at the end of midpregnancy. Low PlGF concentrations during pregnancy are associated with pregnancy complications with recognized later-life cardiovascular risk. We hypothesized that low PlGF concentrations, especially in midpregnancy, identify not only a subset of women at risk for pregnancy complications but also women with greater cardiovascular risk factor burden after pregnancy regardless of pregnancy outcome. METHODS: In a population-based prospective cohort study of 5475 women, we computed gestational age-adjusted multiples of the medians of early pregnancy and midpregnancy PlGF concentrations. Information on pregnancy complications (preeclampsia, small for gestational age, and spontaneous preterm birth) was obtained from hospital registries. Six years after pregnancy, we measured maternal systolic and diastolic blood pressures, cardiac structure (aortic root diameter, left atrial diameter, left ventricular mass, and fractional shortening), carotid-femoral pulse wave velocity, and central retinal arteriolar and venular calibers. Blood pressure was also measured 9 years after pregnancy. RESULTS: Women were on average 29.8 (SD, 5.2) years of age in pregnancy, were mostly European (55.2%), and 14.8% developed a pregnancy complication. Quartile analysis showed that especially women with midpregnancy PlGF in the lowest quartile (the low-PlGF subset) had a larger aortic root diameter (0.40 mm [95% CI, 0.08-0.73]), left atrial diameter (0.34 mm [95% CI, -0.09 to 0.78]), left ventricular mass (4.6 g [95% CI, 1.1-8.1]), and systolic blood pressure (2.3 mm Hg [95% CI, 0.93-3.6]) 6 years after pregnancy than women with the highest PlGF. Linear regression analysis showed that higher midpregnancy PlGF concentrations were associated with a smaller aortic root diameter (-0.24 mm [95% CI, -0.39 to -0.10]), smaller left atrial diameter (-0.75 mm [95% CI, -0.95 to -0.56]), lower left ventricular mass (-3.9 g [95% CI, -5.5 to -2.3]), and lower systolic blood pressure (-1.1 mm Hg [95% CI, -1.7 to -0.46]). These differences persisted after the exclusion of women with complicated pregnancies. CONCLUSIONS: Women with low PlGF in midpregnancy have a greater aortic root diameter, left atrial diameter, and left ventricular mass and higher systolic blood pressure 6 and 9 years after pregnancy compared to women with higher PlGF, including women with uncomplicated pregnancies. The pathophysiological implications of lower PlGF concentrations in midpregnancy might provide insight into the identification of pathways contributing to greater cardiovascular risk factor burden.

Cardiovascular risk model performance in women with and without hypertensive disorders of pregnancy.

OBJECTIVES: Compare the predictive performance of Framingham Risk Score (FRS), Pooled Cohort Equations (PCEs) and Systematic COronary Risk Evaluation (SCORE) model between women with and without a history of hypertensive disorders of pregnancy (hHDP) and determine the effects of recalibration and refitting on predictive performance. METHODS: We included 29 751 women, 6302 with hHDP and 17 369 without. We assessed whether models accurately predicted observed 10-year cardiovascular disease (CVD) risk (calibration) and whether they accurately distinguished between women developing CVD during follow-up and not (discrimination), separately for women with and without hHDP. We also recalibrated (updating intercept and slope) and refitted (recalculating coefficients) the models. RESULTS: Original FRS and PCEs overpredicted 10-year CVD risks, with expected:observed (E:O) ratios ranging from 1.51 (for FRS in women with hHDP) to 2.29 (for PCEs in women without hHDP), while E:O ratios were close to 1 for SCORE. Overprediction attenuated slightly after recalibration for FRS and PCEs in both hHDP groups. Discrimination was reasonable for all models, with C-statistics ranging from 0.70-0.81 (women with hHDP) and 0.72-0.74 (women without hHDP). C-statistics improved slightly after refitting 0.71-0.83 (with hHDP) and 0.73-0.80 (without hHDP). The E:O ratio of the original PCE model was statistically significantly better in women with hHDP compared with women without hHDP. CONCLUSIONS: SCORE performed best in terms of both calibration and discrimination, while FRS and PCEs overpredicted risk in women with and without hHDP, but improved after recalibrating and refitting the models. No separate model for women with hHDP seems necessary, despite their higher baseline risk.

Cardiovascular Risk Factors Track From Mother to Child.

Background Cardiovascular risk factors can track from mother to child by several pathways: pregnancy complications, genetic inheritance, and shared environmental risk factors after pregnancy. The degree of tracking, and to which extent this is influenced by these pathways, is unknown. We hypothesized that cardiovascular risk factors track from mother to child regardless of pregnancy complications and environmental risk factors. We determined the degree of tracking between maternal and offspring micro- and macrovascular cardiovascular risk factors after pregnancy and the extent to which this is influenced by pregnancy complications and shared environmental risk factors. Methods and Results We included 5624 mother-offspring pairs from The Generation R Study, an ongoing prospective, population-based birth cohort. Information on pregnancy complications (preeclampsia, small for gestational age, and preterm birth) was obtained through hospital charts. Mother-offspring associations were assessed 6 years after pregnancy (central retinal arteriolar and venular calibers, body mass index, blood pressure, left atrial diameter, aortic root diameter, left ventricular mass, fractional shortening, and pulse wave velocity) and 9 years after pregnancy (body mass index and blood pressure). We observed that worse cardiovascular parameters in mothers were associated with worse cardiovascular parameters in their offspring 6 and 9 years after pregnancy ( P<0.001). Results were similar when mother-offspring pairs with a previous pregnancy complication were excluded. Conclusions Six and 9 years after pregnancy, an adverse cardiovascular profile in mothers is strongly associated with an adverse cardiovascular profile in their offspring. Results were not attenuated by environmental exposures or a previous pregnancy complication. This supports the hypothesis that cardiovascular risk factors (micro- and macrovascular) track from mother to child, regardless of the course of pregnancy.

Maternal lipid profile 6 years after a gestational hypertensive disorder.

BACKGROUND: Gestational hypertensive disorders (GHDs), including gestational hypertension and preeclampsia, are associated with an increased risk of cardiovascular disease in later life, possibly through an atherogenic lipid profile. OBJECTIVE: The objective of this study is to assess if women with a previous GHD have a more atherogenic lipid profile 6 years after pregnancy compared to women with a previous normotensive pregnancy. METHODS: In a population-based prospective cohort study, we included 4933 women during pregnancy, including 302 women with a GHD. Six years after pregnancy, we determined maternal lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, lipoprotein[a], and apolipoprotein B) and glucose levels. RESULTS: Women with a previous GHD had a more atherogenic lipid profile 6 years after pregnancy compared to women with a previous normotensive pregnancy. These atherogenic lipid profiles were a result of higher levels of triglycerides, low-density lipoprotein cholesterol, and apolipoprotein B and lower levels of high-density lipoprotein cholesterol. Differences in lipid profile between women with a previous GHD and women with a previous normotensive pregnancy were attenuated after adjustment for prepregnancy body mass index. Between women from both groups, no differences were observed in total cholesterol, lipoprotein[a], and glucose levels. CONCLUSION: Women with a previous GHD show a more atherogenic lipid profile 6 years after pregnancy than women with a previous normotensive pregnancy. The increased risk of cardiovascular disease after a GHD might result from an atherogenic lipid profile after pregnancy, primarily driven by prepregnancy body mass index.

Blood Pressure Profile 1 Year After Severe Preeclampsia.

Preeclampsia increases the long-term risk of cardiovascular disease, possibly through occurrence of hypertension after delivery, such as masked hypertension, night-time hypertension, and an adverse systolic night-to-day blood pressure (BP) ratio. These types of hypertension are often unnoticed and can only be detected with ambulatory BP monitoring (ABPM). We aimed to determine hypertension prevalence and 24-hour BP pattern with ABPM and office BP measurements in women 1 year after severe preeclampsia. This is a retrospective cohort study. As part of a follow-up program after severe preeclampsia, 200 women underwent ABPM and an office BP measurement 1 year after delivery. We calculated hypertension prevalence (sustained hypertension, masked hypertension, and white-coat hypertension) and systolic night-to-day BP ratio (dipping pattern). Medical files and questionnaires provided information on preexisting hypertension and antihypertensive treatment. One year after delivery, 41.5% of women had hypertension (sustained hypertension, masked hypertension, or white-coat hypertension) with ABPM. Masked hypertension was most common (17.5%), followed by sustained hypertension (14.5%) and white-coat hypertension (9.5%). With sheer office BP measurement, only 24.0% of women would have been diagnosed hypertensive. Forty-six percent of women had a disadvantageous dipping pattern. Hypertension is common 1 year after experiencing severe preeclampsia. Masked hypertension and white-coat hypertension are risk factors for future cardiovascular disease and can only be diagnosed with ABPM. Therefore, ABPM should be offered to all these women at high risk of developing hypertension and possibly future cardiovascular disease.

Cardiovascular RiskprofilE - IMaging and gender-specific disOrders (CREw-IMAGO): rationale and design of a multicenter cohort study.

BACKGROUND: Reproductive disorders, such as polycystic ovary syndrome (PCOS), primary ovarian insufficiency (POI) and hypertensive pregnancy disorders (HPD) like pre-eclampsia (PE), are associated with an increased risk of cardiovascular disease (CVD). Detection of early signs of cardiovascular disease (CVD), as well as identification of risk factors among women of reproductive age which improve cardiovascular risk prediction, is a challenge and current models might underestimate long-term health risks. The aim of this study is to assess cardiovascular disease in patients with a history of a reproductive disorder by low-dose computed tomography (CT). METHODS: Women of 45 - 55 years, who experienced a reproductive disorder (PCOS, POI, HPD), are invited to participate in this multicenter, prospective, cohort study. Women will be recruited after regular cardiovascular screening, including assessment of classical cardiovascular risk factors. CT of the coronary arteries (both coronary artery calcium scoring (CACS), and contrast-enhanced coronary CT angiography (CCTA)) and carotid siphon calcium scoring (CSC) is planned in 300 women with HPD and 300 women with PCOS or POI. In addition, arterial stiffness (non-invasive pulse wave velocity (PWV)) measurement and cell-based biomarkers (inflammatory circulating cells) will be obtained. DISCUSSION: Initial inclusion is focused on women of 45 - 55 years. However, the age range (40 - 45 years and/or ≥ 55 years) and group composition may be adjusted based on the findings of the interim analysis. Participants can potentially benefit from information obtained in this study concerning their current cardiovascular health and expected future risk of cardiovascular events. The results of this study will provide insights in the development of CVD in women with a history of reproductive disorders. Ultimately, this study may lead to improved cardiovascular prediction models and will provide an opportunity for timely adjustment of preventive strategies. Limitations of this study include the possibility of overdiagnosis and the average radiation dose of 3.5 mSv during coronary and carotid siphon CT, although the increased lifetime malignancy risk is negligible. TRIAL REGISTRATION: Netherlands Trial Register, NTR5531 . Date registered: October 21st, 2015.

Gestational hypertensive disorders and retinal microvasculature: the Generation R Study.

BACKGROUND: Changes in the microvasculature associated with pre-eclampsia and gestational hypertension have been proposed as a potential pathway in the development of cardiovascular disease. We examined whether gestational hypertensive disorders, such as pre-eclampsia and gestational hypertension, are related to the maternal retinal microvasculature status after pregnancy. METHODS: This study is part of an ongoing population-based prospective cohort study. During pregnancy and 6.2 years after the index pregnancy (90% range 5.7-7.4 years), we examined 3391 women with available information on pre-eclampsia, gestational hypertension, and retinal vascular calibers. Retinal arteriolar and venular calibers were measured in the left eye from digitized retinal photographs. RESULTS: Women with pre-eclampsia had smaller retinal arteriolar calibers 6 years after pregnancy than women with a normotensive pregnancy (adjusted difference: -0.40 standard deviation score [SDS]; 95% confidence interval [CI]: -0.62, -0.19). For women with previous gestational hypertension, similar trends were observed (-0.20 SDS; 95% CI: -0.34, -0.05). With respect to retinal venular calibers, we did not observe consistent trends for women with previous pre-eclampsia. However, in women with previous gestational hypertension, we observed larger venular calibers (0.22 SDS; 95% CI: 0.07-0.36) than in women with a previous normotensive pregnancy. The association of gestational hypertensive disorders with retinal vessel calibers was mediated through mean arterial pressure at the time of retinal imaging. CONCLUSIONS: Compared to women with a previous normotensive pregnancy, women with pre-eclampsia and gestational hypertension show an altered status of the microvasculature 6 years after the index pregnancy. This is reflected by smaller retinal arteriolar calibers and wider retinal venular calibers. These microvascular changes may possibly contribute to the development of cardiovascular disease in later life.

Soft versus firm catheters for intrauterine insemination.

BACKGROUND: Intrauterine insemination (IUI) is a recommended treatment for unexplained subfertility. The treatment involves the direct delivery of spermatozoa into the uterus using a catheter. Many factors influence the success of IUI treatments including the type of catheter used. OBJECTIVES: To compare pregnancy-related outcomes from women undergoing intrauterine insemination cycles performed with either soft or firm catheters in subfertile women. SEARCH STRATEGY: We searched the following databases (inception to July 2010) with no language restrictions: Cochrane Menstrual Disorders and Subfertility Group Specialised Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS and OpenSigle. We also searched the conference abstracts in the ISI Web of Knowledge and Google, and conference abstracts and citation lists of relevant publications, reviews and included studies. SELECTION CRITERIA: We included only truly randomised controlled studies of women who underwent IUI using either soft or firm catheter types and reporting data on rates of live birth, clinical pregnancy, multiple pregnancy, miscarriage, ease of introduction of the catheter, occurrence of trauma, or woman's discomfort. DATA COLLECTION AND ANALYSIS: Two review authors screened the titles and abstracts of 78 potentially eligible studies and excluded 66 of these. We critically appraised the full texts of twelve studies and excluded three studies. Nine publications of six studies were remaining. We extracted data from the six remaining studies and there were no disagreements. We assessed risk of bias and pooled dichotomous data and presented the Peto odds ratios (OR) with 95% confidence intervals (CI). MAIN RESULTS: There was no evidence of a significant effect difference regarding the choice of catheter type for any of the outcomes. Three studies reported live birth rates (OR 0.94, 95% CI 0.65 to 1.35) with a translated OR percentages (1.3, 95% CI 0.56 to 3.1) while six studies reported clinical pregnancy rates (OR 1.0, 95% CI 0.73 to 1.35 ). Two studies were pooled for the analysis of miscarriages (OR 1.25, 95% CI 0.49 to 3.22). Results of other adverse outcomes were reported per cycle and were therefore not pooled. AUTHORS' CONCLUSIONS: On the basis of the evidence available in this review, no specific conclusion can be made regarding the superiority of one catheter class over another. Further adequately powered studies reporting on clinical outcomes (e.g. live birth rate) are required. Additional outcomes such as miscarriage rates and measures of discomfort need to be reported.