Preeclampsia is often preceded by abnormal hemodynamic changes with heterogeneous patterns in the first half of pregnancy. We assessed the effect of timely tailored correction of nonphysiological hemodynamic changes on preventing preeclampsia in a high-risk population. Primiparous women with a history of preeclampsia were invited to participate in a longitudinal program in their next pregnancy, including repeated hemodynamic assessments at 12-, 16-, 20- and 30-week gestation additional to regular pregnancy checkups. When at least 2 of the hemodynamic variables were not within physiological reference values, the hemodynamic imbalance between cardiac output and peripheral vascular resistance was counteracted with either labetalol, methyldopa, or nifedipine using a simple treatment algorithm. Normogram-guided women (n=157) were matched to 157 women receiving care as usual (power, 80%; α=0.05). Risk of recurrent preeclampsia was analyzed with logistic regression adjusted for daily low-dose aspirin or calcium supplementation. Hemodynamic changes were considered nonphysiological in 90% of women in the normogram-guided group. Twelve percent of these women developed recurrent preeclampsia compared with 22% in the care-as-usual group (adjusted odds ratio, 0.47 [95% CI, 0.25–0.88]). There were no differences between groups in gestational age at delivery (38 1 and 38 2 weeks in the normogram-guided and care-as-usual groups, respectively) and neonatal birth weight (3148 and 3180 g in the normogram-guided and care-as-usual groups, respectively). Tailored circulatory normalization of nonphysiological hemodynamic changes during pregnancy halves the risk of recurrent preeclampsia, without disadvantageous effects on offspring outcome. This simple and innovative treatment strategy may also be beneficial to other women at increased risk for preeclampsia in pregnancy. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04216706.

Objective: Pregnancy complicated by preeclampsia and fetal growth restriction (FGR) relates to increased risk of cardiovascular disease later in life, but to different extents. Subclinical cardiac alterations precede eminent cardiovascular disease. Speckle-tracking echocardiography is an elegant method to assess subclinical myocardial dysfunction. We performed a myocardial speckle tracking study to evaluate the prevalence of subclinical myocardial dysfunction in former preeclampsia patients (with and without FGR) compared with normotensive women with FGR. Methods: For this cross-sectional study, we retrospectively selected women with a history of normotensive FGR (n = 17), preeclampsia with FGR (n = 26) and preeclampsia without FGR (n = 134) who underwent conventional echocardiography as part of the clinical cardiovascular work-up after complicated pregnancies between 6 months and 4 years postpartum in Maastricht, The Netherlands. We excluded women with chronic hypertension, hypercholesterolemia and obesity. Results: Women with normotensive FGR showed subclinical left ventricular (LV) impairment in systodiastolic function with concentric remodeling, slight alteration in right ventricular systolic function and left atrial strain, similarly to the preeclampsia group independently from the fetal growth. LV hypertrophy was only present in about 10% of cases who experienced preeclampsia (independently from the fetal growth) but not in those with normotensive FGR. Conclusion: Similar to women with a history preeclampsia, women with a history of normotensive pregnancy but with FGR have abnormal myocardial function, shown with speckle-tracking echocardiography. Therefore, both preeclampsia and normotensive FGR should be viewed upon as risk indicator for subclinical myocardial impairment that may benefit from cardiovascular risk management.

Background In‐depth insight into haemodynamic changes during normotensive pregnancy may help identify women at risk for gestational hypertensive complications. Objectives To determine the magnitude of changes in cardiac output and its determinants stroke volume and heart rate, and total peripheral vascular resistance during singleton normotensive and hypertensive pregnancies. Search strategy PubMed (NCBI) and Embase (Ovid) databases were searched from their inception up to November 2019. Selection criteria Studies reporting original measurements of haemodynamic parameters during pregnancy together with a non‐pregnant reference measurement. Studies including women using antihypertensive medication were excluded. Data collection and analysis Pooled mean differences between pregnant and non‐pregnant women, and absolute values of haemodynamic parameters were calculated for predefined gestational intervals using a random‐effects model in normotensive and hypertensive pregnancy. Meta‐regression analysis was used to analyse group differences in adjustments and absolute values during pregnancy. Main results In normotensive pregnancies, cardiac output increased from the first weeks on, reaching its highest level early in the third trimester (mean difference, 1.41 l·min1; 95% CI 1.18–1.63 l·min). In parallel, vascular resistance decreased progressively until its nadir in the early third trimester (mean difference, −331 dyn·sec–1·cm–5; 95% CI −384 to −277 dyn·sec–1·cm–5) and then increased slightly at term. In hypertensive pregnancies, the initial cardiac output increase was higher and vascular resistance did not change throughout gestation compared with reference values. Conclusions Hemodynamic changes in women who eventually develop hypertensive complications are substantially different. Serial monitoring and plotting against developed normograms can identify women at risk and may allow timely intervention. Tweetable abstract Monitoring haemodynamic changes in pregnancy helps identify women at risk for hypertensive complications.

Background: Gestational diabetes mellitus (GDM) is a pregnancy complication characterized by second trimester hyperglycemia. Untreated, GDM is related to an increased risk for adverse pregnancy outcomes. Both beta cell dysfunction and insulin resistance underlie impaired glucose tolerance. Understanding the dominant mechanism predisposing to GDM may be important to provide effective treatment in order to improve perinatal outcomes. We hypothesize that insulin resistance rather that beta cell dysfunction predisposes to GDM. Methods: A 75g oral glucose tolerance test (OGTT) was performed on 2112 second-trimester pregnant women to determine the relationship between insulin resistance (HOMA-IR), beta cell function (HOMA-β), and the prevalence of abnormal glucose handling. Results: High insulin resistance raised the risk of GDM (relative risk (RR) 6.1, 95% confidence interval (CI) (4.4–8.5)), as did beta cell dysfunction (RR 3.8, 95% CI (2.7–5.4)). High insulin resistance, but not beta cell function, enhances the necessity for additional glucose lowering medication on top of a low carbohydrate diet in women diagnosed with GDM. Conclusions: Both high insulin resistance and beta cell dysfunction increase the risk of GDM. As increased insulin resistance, rather than beta cell function, is related to an insufficient response to a low carbohydrate diet, we speculate that insulin sensitizers rather than insulin therapy may be the most targeted therapeutic modality in diet-insensitive GDM.

No abstract