Hypertensive Disorders of Pregnancy and Future Cardiovascular Health.

Hypertensive disorders of pregnancy (HDP) occur in almost 10% of gestations. These women are known to have higher cardiovascular morbidity and mortality later in life in comparison with parous controls who had normotensive pregnancies. Several studies have demonstrated that women with preeclampsia present in a state of segmental impaired myocardial function, biventricular chamber dysfunction, adverse biventricular remodeling, and hypertrophy, a compromised hemodynamic state and indirect echocardiographic signs of localized myocardial ischemia and fibrosis. These cardiac functional and geometric changes are known to have strong predictive value for cardiovascular disease in non-pregnant subjects. A "dose effect" response seems to regulate this relationship with severe HDP, early-onset HDP, coexistence of fetal growth disorders, and recurrence of HDP resulting in poorer cardiovascular measures. The mechanism underlying the relationship between HDP in younger women and cardiovascular disease later in life is unclear but could be explained by sharing of pre-pregnancy cardiovascular risk factors or due to a direct impact of HDP on the maternal cardiovascular system conferring a state of increased susceptibility to future metabolic or hemodynamic insults. If so, the prevention of HDP itself would become all the more urgent. Shortly after delivery, women who experienced HDP express an increased risk of classic cardiovascular risk factors such as essential hypertension, renal disease, abnormal lipid profile, and diabetes with higher frequency than controls. Within one or two decades after delivery, this group of women are more likely to experience premature cardiovascular events, such as symptomatic heart failure, myocardial ischemia, and cerebral vascular disease. Although there is general agreement that women who suffered from HDP should undertake early screening for cardiovascular risk factors in order to allow for appropriate prevention, the exact timing and modality of screening has not been standardized yet. Our findings suggest that prevention should start as early as possible after delivery by making the women aware of their increased cardiovascular risk and encouraging weight control, stop smoking, healthy diet, and daily exercise which are well-established and cost-effective prevention strategies

Preeclampsia: The Relationship between Uterine Artery Blood Flow and Trophoblast Function.

Maternal uterine artery blood flow is critical to maintaining the intrauterine environment, permitting normal placental function, and supporting fetal growth. It has long been believed that inadequate transformation of the maternal uterine vasculature is a consequence of primary defective trophoblast invasion and leads to the development of preeclampsia. That early pregnancy maternal uterine artery perfusion is strongly associated with placental cellular function and behaviour has always been interpreted in this context. Consistently observed changes in pre-conceptual maternal and uterine artery blood flow, abdominal pregnancy implantation, and late pregnancy have been challenging this concept, and suggest that abnormal placental perfusion may result in trophoblast impairment, rather than the other way round. This review focuses on evidence that maternal cardiovascular function plays a significant role in the pathophysiology of preeclampsia

Incidence of postpartum hypertension within 2 years of a pregnancy complicated by pre-eclampsia: a systematic review and meta-analysis.

BACKGROUND: Women with a history of hypertensive disorders of pregnancy (HDP) are at increased long-term risk of cardiovascular disease. However, there has been increasing evidence on the same risks in the months following birth. OBJECTIVES: This review aims to estimate the incidence of hypertension in the first 2 years after HDP. SEARCH STRATEGY: MEDLINE, Embase and Cochrane databases were systematically searched in October 2019. SELECTION CRITERIA: Observational studies comparing hypertension rate following HDP and normotensive pregnancies up to 2 years. DATA COLLECTION AND ANALYSIS: A meta-analysis to calculate the odds ratio (OR) with a 95% confidence interval (CI) and a sub-group analysis excluding women with chronic hypertension were performed. MAIN RESULTS: Hypertension was diagnosed within the first 2 years following pregnancy in 468/1646 (28.4%) and 584/6395 (9.1%) of the HDP and control groups, respectively (OR 6.28; 95% CI 4.18-9.43; I2  = 56%). The risk of hypertension in HDP group was significantly higher in the first 6 months following delivery (OR 18.33; 95% CI 1.35-249.48; I2  = 84%) than at 6-12 months (OR 4.36; 95% CI 2.81-6.76; I2  = 56%) or between 1-2 years postpartum (OR 7.24; 95% CI 4.44-11.80; I2  = 9%). A sub-group analysis demonstrated a similar increase in the risk of developing postpartum hypertension after HDP (OR 5.75; 95% CI 3.92-8.44; I2  = 49%) and pre-eclampsia (OR 6.83; 95% CI 4.25-10.96; I2  = 53%). CONCLUSIONS: The augmented risk of hypertension after HDP is highest in the early postpartum period, suggesting that diagnosis and targeted interventions to improve maternal cardiovascular health may need to be commenced in the immediate postpartum period. TWEETABLE ABSTRACT: The risk of hypertension within 2 years of birth is six-fold higher in women who experienced pre-eclampsia

Are Twin Pregnancies Complicated by Weight Discordance or Fetal Growth Restriction at Higher Risk of Preeclampsia?

Studies have reported controversial findings on the association between fetal growth restriction (FGR) or intertwin weight discordance and the risk of hypertensive disorders of pregnancy (HDP) in twin pregnancies. The aim of this study was to investigate the association between twin growth disorders and HDP. Twin pregnancies resulting in two live births at St George's Hospital between 2000 and 2019 were included. FGR or small-for-gestational-age (SGA) at birth was assessed using singleton and twin reference charts. Intertwin discordance [(large birthweight - small birthweight)/(large birthweight) × 100%)] was calculated. Logistic regression models were performed. SGA (aOR 2.34, 95% CI 1.60-3.44, p < 0.001), intertwin discordance ≥25% (aOR 2.10, 95% CI 1.26-3.49, p = 0.004) and their co-existence (aOR 2.03, 95% CI 1.16-3.54, p = 0.013) were significantly associated with HDP. After adjusting for the known maternal risk factors of HDP and the intertwin discordance, SGA (using the twin charts) was the strongest independent risk factor associated with HDP (aOR 2.12, 95% CI 1.40-3.22, p < 0.001) and preeclampsia (aOR 2.34, 95% CI 1.45-3.76, p < 0.001). This study highlights that the presence of at least one SGA twin is significantly associated with HDP during pregnancy. Therefore, maternal blood pressure should be closely monitored in twin pregnancies complicated by SGA with or without intertwin discordance

Peripartum echocardiographic changes in women with hypertensive disorders of pregnancy

Women with hypertensive disorders of pregnancy (HDP) present with evidence of significant myocardial dysfunction on echocardiographic assessment at the time of diagnosis. Birth not only cures the syndrome of HDP, but is also associated with a reduction in cardiovascular (CV) volume and resistance load in the mother due to the delivery of the fetoplacental unit. The impact of this physiological change on maternal myocardial function in women with HDP has not been systematically evaluated. The aim of this study is to compare echocardiographic findings immediately before and after childbirth in women with HDP. In this prospective longitudinal study, 30 women with a diagnosis of HDP underwent two consecutive transthoracic echocardiography (TTE) examinations: the first prepartum and the second in the early postpartum period. Paired comparisons of these assessments were performed. Left ventricular (LV) concentric remodelling or hypertrophy were found in 21 (70%) patients and there were no significant differences in cardiac morphology indices: LV mass index (78.9±16.3 g/m vs 77.9 ±15.4 g/m , p=0.611) and relative wall thickness (0.45±0.1 vs 0.44±0.1, p=0.453). LV diastolic function did not demonstrate any peripartum variation: left atrial volume (52.40±15.3 vs 50.97±15.6, p=0.433); lateral E' (0.12±0.03 vs 0.12±0.03, p=0.307) and E/E' ratio (7.88±2.19 vs 7.91±1.74, p=0.934). Systolic function indices such as LV ejection fraction (57.5±4.4% vs 56.4±2.1%, p=0.295) and global longitudinal strain (-15.3±2.6% vs -15.1±3.1%, p=0.715) also remained unchanged. Maternal hemodynamic changes associated with birth did not significantly influence peripartum TTE indices in women with HDP. Suboptimal maternal echocardiographic findings in HDP are likely to be the consequence of chronic pregnancy CV load changes or pre-existing maternal CV impairment. Severity and persistence of myocardial dysfunction into the postpartum period may be related to the long-term maternal CV disease legacy of HDP. This article is protected by copyright. All rights reserved. [Abstract copyright: This article is protected by copyright. All rights reserved.

Postpartum cardiovascular function in patients with hypertensive disorders of pregnancy: a longitudinal study

BACKGROUND: Women with a history of hypertensive disorders of pregnancy (HDP) are at increased risk of cardiovascular diseases that are usually mediated by the development of cardiovascular risk factors, such as chronic hypertension, metabolic syndrome or subclinical myocardial dysfunction. Increasing evidence has been showing that little time elapses between the end of pregnancy and the development of these cardiovascular risk factors. OBJECTIVES: To assess the persistence of hypertension and myocardial dysfunction at four months postpartum in a cohort of women with HDP and to compare the echocardiographic parameters between the peripartum and the postpartum period. STUDY DESIGN: In a longitudinal prospective study, a cohort of women with preterm or term HDP and an unmatched group of women with term normotensive pregnancy were recruited. Women with pre-existing chronic hypertension (n=29) were included in the HDP cohort. All participants underwent two cardiovascular assessments: the first was conducted either before or within one week of delivery (V1: peripartum assessment), and the second was between three and 12 months following giving birth (V2: postpartum assessment). The cardiovascular evaluation included blood pressure profile, maternal transthoracic echocardiography (left ventricular mass index (LVMI), relative wall thickness (RWT), left atrial volume index (LAVI), E/A, E/e', peak velocity of tricuspid regurgitation (TR), ejection fraction (EF), and LV global longitudinal strain (GLS) and twist) and metabolic assessment (fasting glycemia, insulin, lipid profile and waist measurement). Echocardiographic data were compared between V1 and V2 using paired t-test or McNemar test in HDP and in the control groups. RESULTS: Among 260 patients with pregnancies complicated by HDP and 33 patients with normotensive pregnancies, 219 (84.2%) and 30 (90.9%) attended postpartum follow-up, respectively. Patients were evaluated at a median (IQR) of 124 (103-145) days after delivery. Paired comparisons of echocardiographic findings demonstrated significant improvements in cardiac remodeling rates (left ventricular mass index (g/m2) 63.4±14.4 vs 78.9±16.2, p<0.0001; relative wall thickness 0.35±0.1 vs 0.42±0.1, p<0.0001), most diastolic indices (E/E' 6.3±1.6 vs 7.4±1.9, p<0.0001), ejection fraction (EF<55%: 9 (4.1%) vs 28 (13.0%), p<0.0001) and global longitudinal strain (-17.3±2.6% vs -16.2±2.4%, p<0.0001) in the postpartum period compared to the peripartum. The same improvements in cardiac indices were observed in the normotensive group. However, at the postnatal assessment, 153/219 (69.9%) had either hypertension (76/219, 34.7%) or an abnormal global longitudinal strain (125/219, 57.1%), 13/67 (19.4%) had metabolic syndrome and 18/67 (26.9%) exhibited insulin resistance. CONCLUSIONS: Although persistent postpartum cardiovascular impairment was evident in a substantial proportion of these patients since more than two-thirds had either hypertension or myocardial dysfunction postpartum, cardiac modifications due to pregnancy-related overload and hypertension were significantly more pronounced in the peripartum than in the postpartum periods

Antioxidants in Pregnancy: Do We Really Need More Trials?

Human pregnancy can be affected by numerous pathologies, from those which are mild and reversible to others which are life-threatening. Among these, gestational diabetes mellitus and hypertensive disorders of pregnancy with subsequent consequences stand out. Health problems experienced by women during pregnancy and postpartum are associated with significant costs to health systems worldwide and contribute largely to maternal mortality and morbidity. Major risk factors for mothers include obesity, advanced maternal age, cardiovascular dysfunction, and endothelial damage; in these scenarios, oxidative stress plays a major role. Markers of oxidative stress can be measured in patients with preeclampsia, foetal growth restriction, and gestational diabetes mellitus, even before their clinical onset. In consequence, antioxidant supplements have been proposed as a possible therapy; however, results derived from large scale randomised clinical trials have been disappointing as no positive effects were demonstrated. This review focuses on the latest evidence on oxidative stress in pregnancy complications, their early diagnosis, and possible therapies to prevent or treat these pathologies

Effectiveness of contingent screening for placenta accreta spectrum disorders based on persistent low‐lying placenta and previous uterine surgery

Objectives Maternal mortality related to placenta accreta spectrum (PAS) disorders remains substantial when diagnosed unexpectedly at delivery. The aim of this study was to evaluate the effectiveness of a routine contingent ultrasound screening program for PAS. Methods This was a retrospective study of data obtained between 2009 and 2019, involving two groups: a screening cohort of unselected women attending for routine mid‐trimester ultrasound assessment and a diagnostic cohort consisting of women referred to the PAS diagnostic service with a suspected diagnosis of PAS. In the screening cohort, women with a low‐lying placenta at the mid‐trimester assessment were followed up in the third trimester, and those with a persistent low‐lying placenta (i.e. placenta previa) and previous uterine surgery were referred to the PAS diagnostic service. Ultrasound assessment by the PAS diagnostic service consisted of two‐dimensional grayscale and color Doppler ultrasonography, and women with a diagnosis of PAS were usually managed with conservative myometrial resection. The final diagnosis of PAS was based on a combination of intraoperative clinical findings and histopathological examination of the surgical specimen. Results In total, 57 179 women underwent routine mid‐trimester fetal anatomy assessment, of whom 220 (0.4%) had a third‐trimester diagnosis of placenta previa. Seventy‐five of these women were referred to the PAS diagnostic service because of a history of uterine surgery, and 21 of 22 cases of PAS were diagnosed correctly (sensitivity, 95.45% (95% CI, 77.16–99.88%) and specificity, 100% (95% CI, 99.07–100%)). Univariate analysis demonstrated that parity ≥ 2 (odds ratio (OR), 35.50 (95% CI, 6.90–649.00)), two or more previous Cesarean sections (OR, 94.20 (95% CI, 22.00–656.00)) and placenta previa (OR, 20.50 (95% CI, 4.22–369.00)) were the strongest risk factors for PAS. In the diagnostic cohort, there were 173 referrals, with one false‐positive and three false‐negative diagnoses, resulting in a sensitivity of 96.63% (95% CI, 90.46–99.30%) and a specificity of 98.81% (95% CI, 93.54–99.97%). Conclusions A contingent screening strategy for PAS is both feasible and effective in a routine healthcare setting. When linked to a PAS diagnostic and surgical management service, adoption of such a screening strategy has the potential to reduce the maternal morbidity and mortality associated with this condition. However, larger prospective studies are necessary before implementing this screening strategy into routine clinical practice

Perinatal outcome of pregnancy complicated by twin anemia–polycythemia sequence: systematic review and meta-analysis

Objective To report the perinatal outcome of monochorionic diamniotic (MCDA) twin pregnancies complicated by twin anemia–polycythemia sequence (TAPS), according to the type of TAPS (spontaneous or postlaser) and the management option adopted. Methods MEDLINE, EMBASE and The Cochrane Library databases were searched for studies reporting on the outcome of twin pregnancies complicated by TAPS. Inclusion criteria were non-anomalous MCDA twin pregnancies with a diagnosis of TAPS. The primary outcome was perinatal mortality; secondary outcomes were neonatal morbidity and preterm birth (PTB). The outcomes were stratified according to the type of TAPS (spontaneous or following laser treatment for twin–twin transfusion syndrome) and the management option adopted (expectant, laser surgery, intrauterine transfusion (IUT) or selective reduction (SR)). Random-effects meta-analysis of proportions was used to analyze the data. Results Perinatal outcome was assessed according to whether TAPS occurred spontaneously or after laser treatment in 506 pregnancies (38 studies). Intrauterine death (IUD) occurred in 5.2% (95% CI, 3.6–7.1%) of twins with spontaneous TAPS and in 10.2% (95% CI, 7.4–13.3%) of those with postlaser TAPS, while the corresponding rates of neonatal death were 4.0% (95% CI, 2.6–5.7%) and 9.2% (95% CI, 6.6–12.3%), respectively. Severe neonatal morbidity occurred in 29.3% (95% CI, 25.6–33.1%) of twins after spontaneous TAPS and in 33.3% (95% CI, 17.4–51.8%) after postlaser TAPS, while the corresponding rates of severe neurological morbidity were 4.0% (95% CI, 3.5–5.7%) and 11.1% (95% CI, 6.2–17.2%), respectively. PTB complicated 86.3% (95% CI, 77.2–93.3%) of pregnancies with spontaneous TAPS and all cases with postlaser TAPS (100% (95% CI, 84.3–100%)). Iatrogenic PTB was more frequent than spontaneous PTB in both groups. Perinatal outcome was assessed according to the management option adopted in 417 pregnancies (21 studies). IUD occurred in 9.8% (95% CI, 4.3–17.1%) of twins managed expectantly and in 13.1% (95% CI, 9.2–17.6%), 12.1% (95% CI, 7.7–17.3%) and 7.6% (95% CI, 1.3–18.5%) of those treated with laser surgery, IUT and SR, respectively. Severe neonatal morbidity affected 27.3% (95% CI, 13.6–43.6%) of twins in the expectant-management group, 28.7% (95% CI, 22.7–35.1%) of those in the laser-surgery group, 38.2% (95% CI, 18.3–60.5%) of those in the IUT group and 23.3% (95% CI, 10.5–39.2%) of those in the SR group. PTB complicated 80.4% (95% CI, 59.8–94.8%), 73.4% (95% CI, 48.1–92.3%), 100% (95% CI, 76.5–100%) and 100% (95% CI, 39.8–100%) of pregnancies after expectant management, laser surgery, IUT and SR, respectively. Conclusions The present meta-analysis provides pooled estimates of the risks of perinatal mortality, neonatal morbidity and PTB in twin pregnancies complicated by TAPS, stratified by the type of TAPS and the management option adopted. Although a direct comparison could not be performed, the results from this systematic review suggest that spontaneous TAPS may have a better prognosis than postlaser TAPS. No differences in terms of mortality and morbidity were observed when comparing different management options for TAPS, although these findings should be interpreted with caution in view of the limitations of the included studies. Individualized prenatal management, taking into account the severity of TAPS and gestational age, is currently the recommended strategy

Perinatal Outcomes of Small for Gestational Age in Twin Pregnancies: Twin vs. Singleton Charts.

Twin pregnancies are commonly assessed using singleton growth and birth weight reference charts. This practice has led to a significant number of twins labelled as small for gestational age (SGA), causing unnecessary interventions and increased risk of iatrogenic preterm birth. However, the use of twin-specific charts remains controversial. This study aims to assess whether twin-specific estimated fetal weight (EFW) and birth weight (BW) charts are more predictive of adverse outcomes compared to singleton charts. Centiles of EFW and BW were calculated using previously published singleton and twin charts. Categorical data were compared using Chi-square or McNemar tests. The study included 1740 twin pregnancies, with the following perinatal adverse outcomes recorded: perinatal death, preterm birth <34 weeks, hypertensive disorders of pregnancy (HDP) and admissions to the neonatal unit (NNU). Twin-specific charts identified prenatally and postnatally a smaller proportion of infants as SGA compared to singleton charts. However, twin charts showed a higher percentage of adverse neonatal outcomes in SGA infants than singleton charts. For example, perinatal death (SGA 7.2% vs. appropriate for gestational age (AGA) 2%, p < 0.0001), preterm birth <34 weeks (SGA 42.1% vs. AGA 16.4%, p < 0.0001), HDP (SGA 21.2% vs. AGA 13.5%, p = 0.015) and NNU admissions (SGA 69% vs. AGA 24%, p < 0.0001), when compared to singleton charts (perinatal death: SGA 2% vs. AGA 1%, p = 0.029), preterm birth <34 weeks: (SGA 20.6% vs. AGA 17.4%, p = 0.020), NNU admission: (SGA 34.5% vs. AGA 23.9%, p < 0.000). There was no significant association between HDP and SGA using the singleton charts (p = 0.696). In SGA infants, according to the twin charts, the incidence of abnormal umbilical artery Doppler was significantly more common than in SGA using the singleton chart (27.0% vs. 8.1%, p < 0.001). In conclusion, singleton charts misclassify a large number of twins as at risk of fetal growth restriction. The evidence suggests that the following twin-specific charts could reduce unnecessary medical interventions prenatally and postnatally