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Do modifiable risk factors for cardiovascular disease post-pregnancy influence the association between hypertensive disorders of pregnancy and cardiovascular health outcomes? A systematic review of observational studies.
Hutchesson, M, Campbell, L, Leonard, A, Vincze, L, Shrewsbury, V, Collins, C, Taylor, R
Pregnancy hypertension. 2022;:138-147
Abstract
Hypertensive disorders of pregnancy (HDP) are associated with increased risk of developing cardiovascular disease (CVD) in later life. This systematic review aimed to evaluate the impact of modifiable risk factors for CVD following pregnancy on the relationship between HDP and cardiovascular health outcomes. Seven databases (Medline, CENTRAL, CINAHL, Cochrane Reviews, Embase, PsycINFO and Scopus) were searched from date of inception to July 24, 2019. Observational studies that included female adults with a history of HDP and analysed whether modifiable risk factors for CVD following pregnancy (dietary intake, physical activity, smoking status, alcohol intake, body weight and mental health status) influenced associations between HDP and cardiovascular health outcomes (morbidity, mortality or related risk markers) were eligible for inclusion. In total, 4704 articles were identified, with 11 studies included. The modifiable risk factors measured included body weight (11 studies), physical activity and dietary intake (one study) and smoking (one study). Overall, five of seven studies provided convincing evidence that the relationship between HDP and blood pressure was adversely impacted by excess body weight post-pregnancy. The current systematic review provides evidence that excess body weight post-pregnancy impacts associations between HDP and hypertension in later life. However, there is a lack of evidence exploring the impact of a variety of modifiable risk factors for CVD on associations between HDP and cardiovascular health outcomes. This evidence is imperative to inform development of effective CVD prevention interventions for women with a history of HDP.
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The P4 study: Subsequent pregnancy maternal physiology after hypertensive and normotensive pregnancies.
Kennedy, R, Roberts, L, Davis, G, Mangos, G, Pettit, F, Brown, MA, O'Sullivan, AJ, Henry, A
Pregnancy hypertension. 2022;:29-34
Abstract
OBJECTIVES Hypertensive disorders of pregnancy are associated with subsequent increased risk of cardiometabolic disease. Adverse cardiometabolic measures are noted soon after hypertensive versus normotensive pregnancy (NP); to what degree these persist into a subsequent pregnancy (SP) is unknown. This study aimed to assess women's physiology early in SP after hypertensive pregnancy (HP: preeclampsia or gestational hypertension) or NP and compare SP to 6 months postpartum findings from the index pregnancy. STUDY DESIGN Prospective sub-study of the P4 (Postpartum, Physiology, Psychology and Paediatric) observational cohort. Measurements six months after NP versus HP, and the SP at 11-13 weeks gestation. MAIN OUTCOME MEASURES Blood pressure (BP), blood and urine tests (urine ACR, HOMA-IR, LDL cholesterol), body composition, and contribution of maternal characteristics and inter-pregnancy factors to BP and body fat (FM%) in SP. RESULTS 49 women (34 NP, 15 HP). In the SP, post-HP women had higher BP (112/70 mmHg HP vs 102/64 mmHg NP; p < .001), with no significant drop from six months postpartum to early SP. On regression analysis, systolic and diastolic BP at 6-months were the major predictors for SP systolic (p < 0.001) and diastolic (p = 0.009) BP respectively in the SP. Longer interpregnancy interval and increased FM% 6-months postpartum were associated with higher SP FM% (p < 0.001). CONCLUSIONS BP and body fat six months postpartum were similar early in the SP for HP group, and postpartum BP and FM% were major predictors of their corresponding SP measurements. Postpartum/inter-pregnancy intervention programs to improve these cardiometabolic risk markers might help improve women's long-term health and require investigation.
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Probiotics for preventing gestational diabetes.
Davidson, SJ, Barrett, HL, Price, SA, Callaway, LK, Dekker Nitert, M
The Cochrane database of systematic reviews. 2021;(4):CD009951
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Abstract
BACKGROUND Gestational diabetes mellitus (GDM) is associated with a range of adverse pregnancy outcomes for mother and infant. The prevention of GDM using lifestyle interventions has proven difficult. The gut microbiome (the composite of bacteria present in the intestines) influences host inflammatory pathways, glucose and lipid metabolism and, in other settings, alteration of the gut microbiome has been shown to impact on these host responses. Probiotics are one way of altering the gut microbiome but little is known about their use in influencing the metabolic environment of pregnancy. This is an update of a review last published in 2014. OBJECTIVES To systematically assess the effects of probiotic supplements used either alone or in combination with pharmacological and non-pharmacological interventions on the prevention of GDM. SEARCH METHODS We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (20 March 2020), and reference lists of retrieved studies. SELECTION CRITERIA Randomised and cluster-randomised trials comparing the use of probiotic supplementation with either placebo or diet for the prevention of the development of GDM. Cluster-randomised trials were eligible for inclusion but none were identified. Quasi-randomised and cross-over design studies were not eligible for inclusion in this review. Studies presented only as abstracts with no subsequent full report of study results were only included if study authors confirmed that data in the abstract came from the final analysis. Otherwise, the abstract was left awaiting classification. DATA COLLECTION AND ANALYSIS Two review authors independently assessed study eligibility, extracted data and assessed risk of bias of included studies. Data were checked for accuracy. MAIN RESULTS In this update, we included seven trials with 1647 participants. Two studies were in overweight and obese women, two in obese women and three did not exclude women based on their weight. All included studies compared probiotics with placebo. The included studies were at low risk of bias overall except for one study that had an unclear risk of bias. We excluded two studies, eight studies were ongoing and three studies are awaiting classification. Six included studies with 1440 participants evaluated the risk of GDM. It is uncertain if probiotics have any effect on the risk of GDM compared to placebo (mean risk ratio (RR) 0.80, 95% confidence interval (CI) 0.54 to 1.20; 6 studies, 1440 women; low-certainty evidence). The evidence was low certainty due to substantial heterogeneity and wide CIs that included both appreciable benefit and appreciable harm. Probiotics increase the risk of pre-eclampsia compared to placebo (RR 1.85, 95% CI 1.04 to 3.29; 4 studies, 955 women; high-certainty evidence) and may increase the risk of hypertensive disorders of pregnancy (RR 1.39, 95% CI 0.96 to 2.01, 4 studies, 955 women), although the CIs for hypertensive disorders of pregnancy also indicated probiotics may have no effect. There were few differences between groups for other primary outcomes. Probiotics make little to no difference in the risk of caesarean section (RR 1.00, 95% CI 0.86 to 1.17; 6 studies, 1520 women; high-certainty evidence), and probably make little to no difference in maternal weight gain during pregnancy (MD 0.30 kg, 95% CI -0.67 to 1.26; 4 studies, 853 women; moderate-certainty evidence). Probiotics probably make little to no difference in the incidence of large-for-gestational age infants (RR 0.99, 95% CI 0.72 to 1.36; 4 studies, 919 infants; moderate-certainty evidence) and may make little to no difference in neonatal adiposity (2 studies, 320 infants; data not pooled; low-certainty evidence). One study reported adiposity as fat mass (MD -0.04 kg, 95% CI -0.12 to 0.04), and one study reported adiposity as percentage fat (MD -0.10%, 95% CI -1.19 to 0.99). We do not know the effect of probiotics on perinatal mortality (RR 0.33, 95% CI 0.01 to 8.02; 3 studies, 709 infants; low-certainty evidence), a composite measure of neonatal morbidity (RR 0.69, 95% CI 0.36 to 1.35; 2 studies, 623 infants; low-certainty evidence), or neonatal hypoglycaemia (mean RR 1.15, 95% CI 0.69 to 1.92; 2 studies, 586 infants; low-certainty evidence). No included studies reported on perineal trauma, postnatal depression, maternal and infant development of diabetes or neurosensory disability. AUTHORS' CONCLUSIONS Low-certainty evidence from six trials has not clearly identified the effect of probiotics on the risk of GDM. However, high-certainty evidence suggests there is an increased risk of pre-eclampsia with probiotic administration. There were no other clear differences between probiotics and placebo among the other primary outcomes. The certainty of evidence for this review's primary outcomes ranged from low to high, with downgrading due to concerns about substantial heterogeneity between studies, wide CIs and low event rates. Given the risk of harm and little observed benefit, we urge caution in using probiotics during pregnancy. The apparent effect of probiotics on pre-eclampsia warrants particular consideration. Eight studies are currently ongoing, and we suggest that these studies take particular care in follow-up and examination of the effect on pre-eclampsia and hypertensive disorders of pregnancy. In addition, the underlying potential physiology of the relationship between probiotics and pre-eclampsia risk should be considered.
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Association between abnormal maternal serum levels of vitamin B12 and preeclampsia: a systematic review and meta-analysis.
Mardali, F, Fatahi, S, Alinaghizadeh, M, Kord Varkaneh, H, Sohouli, MH, Shidfar, F, Găman, MA
Nutrition reviews. 2021;(5):518-528
Abstract
CONTEXT Some evidence has shown an association between maternal vitamin B12 levels and the development of preeclampsia in pregnant women, but the relationship between preeclampsia and vitamin B12 is not clear. OBJECTIVE The aim of this systematic review was to compare serum vitamin B12 levels in women with preeclampsia with those in normotensive pregnant women. DATA SOURCES The PubMed/MEDLINE, Scopus, and Web of Science databases were searched up to August 2019, along with the reference lists of included articles. STUDY SELECTION The literature was searched for observational studies that investigated vitamin B12 levels in women with preeclampsia. DATA EXTRACTION Data were extracted independently by 2 authors. Data were pooled using a random-effects model. RESULTS Vitamin B12 levels in women with preeclampsia were significantly lower than those in healthy women (mean, -15.24 pg/mL; 95%CI, -27.52 to -2.954; P < 0.015), but heterogeneity between studies was high (I2 = 97.8%; P = 0.0103). Subgroup analyses based on folic acid supplementation, homocysteine concentrations, and gestational age at the time of sampling for vitamin B12 assessment did not identify the sources of heterogeneity. CONCLUSIONS Women with preeclampsia had significantly lower vitamin B12 concentrations than normotensive pregnant women.
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Vitamin D modulates the transcription factors of T cell subsets to anti-inflammatory and regulatory profiles in preeclampsia.
Ribeiro, VR, Romao-Veiga, M, Nunes, PR, Matias, ML, Peracoli, JC, Peracoli, MTS
International immunopharmacology. 2021;(Pt B):108366
Abstract
Vitamin D (VD) is a multifunctional prohormone and low VD status in pregnancy may contribute to the risk of adverse perinatal outcomes, such as preeclampsia (PE). This molecule may modulate the polarization of T cell subsets during gestation. This study evaluated the in vitro immunomodulatory effect of VD [1,25(OH)2D3] on the gene expression of transcription factors and on cytokine production by T cell subsets. Twenty pregnant women with PE and twenty normotensive (NT) pregnant women were studied. Plasma concentration of VD, [25(OH)D3], was evaluated by chemiluminescence. PBMCs from preeclamptic and NT pregnant women were cultured in the absence or presence of VD to determine gene expression of T-bet (Th1), GATA-3 (Th2), RORγt, and RUNX1 (Th17), FoxP3 (regulatory T cell- Treg), and the receptors of VD (VDR) and IL-23 (IL-23R) by quantitative PCR. The concentration of cytokines in the PBMC supernatant culture was determined by cytometric bead array and ELISA immunoassay. The results showed that plasmatic levels of VD were significantly lower in the PE group. The treatment of PBMCs from PE pregnant women with VD induced downregulation of genes related to inflammatory profiles (Th1 and Th17), as well as an increase of the Th2 and Treg profiles. Thus, VD treatment decreased the release of IFN-γ, TNF-α, IL-17, IL-6, and IL-23 while it increased the levels of IL-10 in the PE group. VD induces an immunomodulatory effect in T cell subsets from pregnant women with PE, polarizing these cells to an anti-inflammatory and regulatory profile.
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Association of pre-pregnancy subclinical insulin resistance with cardiac dysfunction in healthy nulliparous women.
Psoinos, RBC, Morris, EA, McBride, CA, Bernstein, IM
Pregnancy hypertension. 2021;:11-16
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Abstract
OBJECTIVES To investigate the association between pre-pregnancy subclinical insulin resistance and cardiovascular dysfunction in healthy nulliparous women, and with hypertension in subsequent pregnancy. STUDY DESIGN Secondary analysis of a single center prospective observational study conducted November 2011-June 2014. Healthy nulliparous women underwent detailed cardiovascular and metabolic assessment. Insulin resistance was determined by homeostasis model assessment (HOMA-IR). Associations of HOMA-IR with metabolic and cardiovascular measurements were assessed with Spearman correlations. Charts were reviewed in women who conceived singleton pregnancies. MAIN OUTCOME MEASURES Metabolic measurements included serum glucose, insulin, creatinine, CRP, and lipids. HOMA-IR was calculated using fasting serum insulin and glucose. Indices of cardiovascular stiffness were determined from pulse wave velocity and response to volume challenge. Pregnancy outcomes included delivery mode and gestational age, birthweight, and hypertension. RESULTS HOMA-IR was positively associated with BMI (r = 0.462, p < 0.001), body fat percentile (r = 0.463, p < 0.001), CRP (r = 0.364, p = 0.003), and negatively associated with serum HDL (r = -0.38, p = 0.002) and creatinine (r = -0.242, p = 0.049). HOMA-IR was positively associated with blood pressure (r = 0.347, p = 0.004), resting heart rate (r = 0.433, p = <0.001), response to volume challenge (r = 0.325, p < 0.01). Increased HOMA-IR was associated with a faster cardiac ejection time in response to volume challenge (r = -0.415, p < 0.001), which is a marker of decreased cardiac compliance to volume increase, or cardiac stiffness. CONCLUSION HOMA-IR is associated with pre-pregnancy cardiac stiffness. Cholesterol was not associated with cardiovascular dysfunction. A non-significant trend was observed between HOMA-IR and hypertension in subsequent pregnancy.
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Association of Preeclampsia With Incident Stroke in Later Life Among Women in the Framingham Heart Study.
de Havenon, A, Delic, A, Stulberg, E, Sheibani, N, Stoddard, G, Hanson, H, Theilen, L
JAMA network open. 2021;(4):e215077
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Abstract
IMPORTANCE Contemporary research suggests an association between preeclampsia and later-life stroke among women. To our knowledge, no research to date has accounted for the time-varying nature of shared risk factors for preeclampsia and later-life stroke incidence. OBJECTIVE To assess the relative risk of incident stroke in later life among women with and without a history of preeclampsia after accounting for time-varying covariates. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study was a secondary analysis of data from the Framingham Heart Study, which was conducted from 1948 to 2016. Women were included in the analysis if they were stroke free at enrollment and had a minimum of 3 study visits and 1 pregnancy before menopause, hysterectomy, or age 45 years. Data on vascular risk factors, history of preeclampsia, and stroke incidence were collected biannually. Participants were followed up until incident stroke or censorship from the study. Marginal structural models were used to evaluate the relative risk of incident stroke among participants with and without a history of preeclampsia after accounting for time-varying covariates. Data were analyzed from May 2019 to December 2020. EXPOSURES Presence or absence of preeclampsia among women with 1 or more pregnancies. MAIN OUTCOMES AND MEASURES Incident stroke in later life. RESULTS A total of 1435 women (mean [SD] age, 44.4 [7.7] years at the beginning of the study; 100% White) with 41 422 person-years of follow-up were included in the analytic sample. Of those, 169 women had a history of preeclampsia, and 231 women experienced strokes during follow-up. At baseline, women with preeclampsia were more likely to be younger, to be receiving cholesterol-lowering medications, to have lower cholesterol and higher diastolic blood pressure, and to currently smoke. The association between preeclampsia and stroke in the marginal structural model was only evident when adjustment was made for all vascular risk factors over the life course, which indicated that women with a history of preeclampsia had a higher risk of stroke in later life compared with women without a history of preeclampsia (relative risk, 3.79; 95% CI, 1.24-11.60). CONCLUSIONS AND RELEVANCE The findings of this cohort study suggest that preeclampsia may be a risk factor for later-life stroke among women after adjustment for time-varying vascular and demographic factors. Future research is warranted to fully explore the mediation of this association by midlife vascular risk factors.
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Blood pressure postpartum (BP2) RCT protocol: Follow-up and lifestyle behaviour change strategies in the first 12 months after hypertensive pregnancy.
Henry, A, Arnott, C, Makris, A, Davis, G, Hennessy, A, Beech, A, Pettit, F, Se Homer, C, Craig, ME, Roberts, L, et al
Pregnancy hypertension. 2020;:1-6
Abstract
OBJECTIVES Women who had hypertensive disorders of pregnancy (HDP) are twice as likely to experience maternal cardiovascular disease later in life. The primary aim of this study (BP2) is to compare outcomes of 3 different management strategies, including lifestyle behaviour change (LBC), in the first 12 months postpartum in women who had HDP in their preceding pregnancy. Secondary aims include assessing the effects on other cardiometabolic parameters. STUDY DESIGN Three-arm multicentre randomised trial in metropolitan Australian hospitals, (registration: ACTRN12618002004246) target sample size 480. Participants are randomised to one of three groups: 1) Optimised usual care: information package and family doctor follow-up 6 months postpartum 2) Brief intervention: information package as per group 1, plus assessment and brief LBC counselling at a specialised clinic with an obstetric physician and dietitian 6 months postpartum 3) Extended intervention: as per group 2 plus enrolment into a 6 month telephone-based LBC program from 6 to 12 months postpartum. All women have an outcome assessment at 12 months. MAIN OUTCOME MEASURES Primary outcomes: (a) BP change or (b) weight change and/or waist circumference change. SECONDARY OUTCOMES maternal health-related quality of life, engagement and retention in LBC program, biochemical markers, vascular function testing, infant weight trajectory, incremental cost-effectiveness ratios. The study is powered to detect a 4 mmHg difference in systolic BP between groups, or a 4 kg weight loss difference/2cm waist circumference change. CONCLUSIONS BP2 will provide evidence regarding the feasibility and effectiveness of postpartum LBC interventions and structured clinical follow-up in improving cardiovascular health markers after HDP.
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Maternal prepregnancy overweight and obesity and the risk of preeclampsia: A meta-analysis of cohort studies.
He, XJ, Dai, RX, Hu, CL
Obesity research & clinical practice. 2020;(1):27-33
Abstract
OBJECTIVE The aim of our meta-analysis was to explore whether overweight and obesity was associated with preeclampsia or not. DESIGN Three databases were systematically reviewed and reference lists of relevant articles were checked. Meta-analysis of published cohort studies comparing whether overweight and obesity was associated with preeclampsia and adjusting for potential confounding factors. Calculations of pooled estimates were conducted in random-effects models. Heterogeneity was tested by using Chi-square test with Cochrane and heterogeneity was explored with meta-regression. Publication bias was estimated from Egger's test (linear regression method) and Begg's test (rank correlation method). RESULTS Nineteen studies met the inclusion criteria. The meta-analysis showed that overweight and obesity was associated with an increased risk of preeclampsia. The aOR calculated for 13 studies (compared overweight to normal weight) was 1.71, 95% CI (1.52, 1.91) for random-effects models and 19 studies (compared obesity to normal weight) was 2.48, 95% CI (2.05, 2.90) for random-effects models, stratified analyses showed no differences regarding quality grade, location of study and period of anthropometric measurement. There was no indication of a publication bias either from the result of Egger's test or Begg's test. CONCLUSIONS Our results suggested that prepregnancy maternal overweight and obesity are significantly associated with an increased risk of preeclampsia.
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Systematic and meta-analysis of factors associated with preeclampsia and eclampsia in sub-Saharan Africa.
Meazaw, MW, Chojenta, C, Muluneh, MD, Loxton, D
PloS one. 2020;(8):e0237600
Abstract
BACKGROUND Preeclampsia and eclampsia are common complications of pregnancy globally, including sub-Saharan African (SSA) countries. Although it has a high burden on maternal and neonatal mortality and morbidity, evidence on the risk of the problem is limited. Therefore, the aim of this review was to examine the factors associated with preeclampsia and eclampsia among mothers in SSA countries. METHODS We searched article from SSA countries using electronic database MEDLINE, EMBASE, PubMed, CINAHL published in English from January 2000 to May 2020. Two reviewers independently screened, extracted and assessed the quality of the articles. Both random and fixed effect model were used for analysis. Heterogeneity of the studies and publication bias were checked. STATA 16 used for analysis. RESULTS Fifty-one studies met the inclusion criteria and included in this review. The following factors were identified through meta-analysis: being primiparous (OR: 2.52; 95% CI:1.19, 3.86), previous history of maternal preeclampsia/eclampsia (OR:5.6; 95% CI:1.82, 9.28), family history of preeclampsia/eclampsia (OR:1.68; 95% CI:1.26, 2.11), high maternal body mass index (OR: 1.69; 95% CI:1.17, 2.21), chronic hypertension (OR: 2.52; 95% CI:1.29, 3.74), anaemia during pregnancy (OR: 3.22; 95% CI:2.70, 3.75) and lack of antenatal care visits (OR: 2.71; 95% CI:1.45, 3.96). There was inconclusive evidence for a relationship with a number of other factors, such as nutrition and related factors, antenatal care visits, birth spacing, and other factors due to few studies found in our review. CONCLUSIONS The risk of preeclampsia and eclampsia is worse among women who have a history of preeclampsia/eclampsia (either themselves or family members), primiparous, obesity and overweight, living with chronic disease, having anaemia during pregnancy and absence from ANC visits. Therefore, investment must be made in women's health needs to reduce the problem and health service providers need to give due attention to high-risk women.