Abstract
Introduction
The primary concern for women who have experienced peripartum cardiomyopathy (PPCM) is the safety of a subsequent pregnancy (SSP). To maximie decision-making, facilitate effective patient counselling, and ultimately improve maternal and fetal outcomes as a whole, it is critical to comprehend the outcomes of SSP in women who have previously experienced PPCM. This study aimed to evaluate the outcomes of SSP in women with PPCM.
Methods
Three databases (PubMed, Scopus, and ScienceDirect) were used to identify relevant studies prior to 17 October 2023. A total of 662 studies were reviewed. Following the abstract and full-text screenings, 18 observational studies were included, out of which 2 were deemed suitable for inclusion in this meta-analysis. The quality assessment was conducted using the Newcastle-Ottawa Scale.
Results
This study has a total of 487 SSPs. Although recovered left ventricular (LV) function before entering SSP has the potential to be a beneficial prognostic factor, recovered LV function still has a substantial risk of relapse. The mortality rate of PPCM in an SSP ranged from 0% to 55.5%. Persistent LV dysfunction was significantly associated with an increased mortality rate (OR 13.17; 95% CI 1.54 to 112.28; p=0.02) and lower LV ejection fraction (MD −12.88; 95% CI −21.67 to −4.09; p=0.004). Diastolic and right ventricular functions remained unchanged before SSP and at follow-up. The majority of the SSP was observed alongside hypertension, while pre-eclampsia emerged as the predominant hypertensive complication in most studies.
Conclusion
SSP increases the risk of relapse and mortality in women with a previous history of PPCM. Persistent LV dysfunction prior to the SSP has a higher mortality risk compared with recovered LV function. SSP was also associated with the worsening of LV echocardiography parameters.
Keywords: Cardiomyopathies, Pregnancy, Heart Failure, Systematic Reviews as Topic, Meta-Analysis
WHAT IS ALREADY KNOWN ON THIS TOPIC
Research on the outcomes of subsequent pregnancies in peripartum cardiomyopathy (PPCM) has yielded conflicting results, with some studies suggesting an increased risk of recurrence and adverse events, while others report more favourable outcomes, highlighting the need for further investigation and consensus in this complex and controversial area of maternal health.
WHAT THIS STUDY ADDS
Subsequent pregnancy poses an elevated risk of relapse and mortality in women with a history of PPCM, particularly for those who maintain persistent left ventricular (LV) dysfunction before the subsequent pregnancy, as they exhibit a heightened mortality risk compared with those with recovered LV function. Additionally, subsequent pregnancy is linked to a deterioration in LV echocardiography parameters.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
Considering the potential for deteriorating LV function, the risk of PPCM relapse and mortality of subsequent pregnancy in women with a history of PPCM, it is recommended to prevent further pregnancies in both patients with persistent and recovered LV function to prioritise maternal well-being.
Introduction
Peripartum cardiomyopathy (PPCM) is a rare but potentially life-threatening condition characterised by heart failure (HF) due to left ventricular (LV) systolic dysfunction towards the end of pregnancy or in the early postpartum period, with the absence of any other cause of HF.1–3 Genetics, multiple pregnancies, underweight, pre-eclampsia, infection and hormonal changes were identified as the predictor factors for the incidence of PPCM.4 The prevalence of PPCM varies depending on the region, it happens in 1:100–1:4000 live births in the USA.5 As of 30 April 2016, a worldwide registry on PPCM had recorded 500 cases, with the incidence varying by race: Caucasian (34%), black African (25.8%), Asian (21.8%) and Middle Eastern (16.4%).6 PPCM is associated with significant morbidity and mortality. Mortality rates of PPCM patients, especially in the USA, vary between 7% and 20% after a mean follow-up of 6.3–8.6 years.7 In a retrospective study including 182 PPCM patients, 46 of them had major adverse events, and 13 patients died due to PPCM.8
The safety of a subsequent pregnancy (SSP) is a primary issue among women who have experienced PPCM. SSP in PPCM is linked to a higher likelihood of experiencing recurrent cardiac dysfunction, clinical deterioration and mortality.9 10 In 191 patients with SSP, PPCM recurrence rate was higher (48% vs 23%) in patients with persistent LV dysfunction before SSP compared with those who have recovered LV function (LV ejection fraction (LVEF) ≥50%). After 5 years of follow-up on 45 patients with SSP, the adverse outcome was significantly higher in a group with persistent LV dysfunction (53.3%), compared with the recovered LV function group (20%), with the mortality rate was 13.33%.11 However, recovered LV function does not provide a guarantee of an uncomplicated SSP.12 Some studies also found that SSP in patients with PPCM was well tolerated with no deterioration in cardiac function.13 14
Understanding the outcomes of SSP in women with a history of PPCM is paramount for both healthcare providers and affected individuals. The utilisation of this approach has the potential to optimise clinical decision-making, facilitate effective patient counselling and ultimately increase the overall maternal and fetal outcomes. To address the issue, this systematic review and meta-analysis sought to systematically analyse, from published literature, the outcomes of SSP in women with PPCM.
Materials and methods
This systematic review and meta-analysis was conducted in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline.15 This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the protocol number CRD42023468291.
Study eligibility
We included studies that fulfilled the following eligibility requirements: (1) observational studies (cohort or case–control), cross-sectional and randomised controlled trials if available; (2) women with SSP and PPCM according to the latest European Society of Cardiology (ESC) 2019 PPCM diagnosis criteria; (3) patients without pre-existing heart disease. Review articles, letters, commentaries, case reports and case series were excluded from the study. Only articles written and published in English were included with no restrictions in regards to dates. PPCM diagnosis criteria were defined by using the standards of European Society of Cardiology (ESC) 2019 PPCM diagnosis criteria are as follows: (1) HF secondary to LV systolic dysfunction with an LVEF<45%; (2) occurrence towards the end of pregnancy or in the months following delivery and (3) no other identifiable cause of HF.9
Search strategy and data extraction
A systematic literature search was performed on PubMed, Scopus and ScienceDirect on 17 October 2023, using search terms: (“peripartum cardiomyopathy” OR “peripartum cardiomyopathies” OR “peripartum myocardiopathy” OR “peripartum myocardiopathies” OR “peripartum myocardial disease” OR “peripartum myocardial diseases”) AND (pregnant OR pregnancy OR pregnancies OR gestation). To identify eligible literature, two reviewers (MAW and GAL) conducted abstract and full-text screenings using the Rayyan software. Disagreements were resolved by consensus with the third reviewer (RM). All identified articles were assessed using the inclusion and exclusion criteria.
From each included study, the following data were extracted: (1) first author and publication year; (2) study design and location; (3) patient characteristics (including maternal age and ethnicity) and (4) outcomes. The outcome was defined as (1) relapse of PPCM; (2) all-cause mortality; (3) echocardiographic findings at the time of index PPCM diagnosis, before SSP, after SSP delivery and at follow-up and (4) pregnancy-related outcome and complications.
Quality assessment
The risk of bias of the studies included in the analysis was assessed independently by two reviewers (AAR and HAZ) using the Newcastle-Ottawa Scale. Each study was assigned a score on a scale of 0–9. Research studies with a score of 7 or higher were considered to have a high level of quality. Any disagreements were resolved by consensus with the third reviewer (RM).
Statistical analysis
The study compared outcomes for binary endpoints by using pooled OR along with 95% CIs. On the other hand, continuous endpoints were compared using mean difference (MD) accompanied by 95% CIs. Heterogeneity was assessed by using the I² statistic with a value of <25%, 26–50% and >50% were considered as low, moderate and high degrees of heterogeneity, respectively. When the heterogeneity test results are low or moderate, a fixed effect measure is used, and while the heterogeneity is high, a random effect measure is used. All statistical analyses were performed by using Review Manager (RevMan) software V.5.4.
Results
Search results, study characteristics and quality assessment
The initial search yielded 662 relevant studies from peer-reviewed databases, as detailed in figure 1. After removing duplicate records, 508 articles were screened for its title and abstracts. The remaining 25 articles were evaluated for their full text, and 7 were excluded. This systematic review and meta-analysis included 18 observational studies with a total of 487 SSPs (range: 7–75 SSPs), which consisted of 8 prospective cohort studies, 9 retrospective cohort studies and 1 case–control study. Most of the included studies were conducted in USA (n=5), followed by Brazil (n=3). Table 1 presents detailed information regarding the characteristics of each study, as well as the reported outcomes. Based on the quality assessment criteria, all but one of the studies were deemed to be of good quality. Online supplemental table 1 provides the risk of bias summary.
Figure 1.

PRISMA flow diagram for study selection. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Table 1.
Characteristics of included studies
| Authors | Year | Study type | Country | SSP reported | Patients’ characteristic | Outcomes reported |
| Albanesi Filho et al 14 | 1999 | Prospective cohort study | Brazil | 12 | Age: 19–44 (mean 32) race: 9 non-whites | NYHA FC Mortality Pregnancy complication (increased heart size, increased heart size+pre-eclampsia) Pregnancy outcome |
| Codsi et al 16 | 2018 | Retrospective cohort study | USA | 43 | Race: 6 white, 3 black | Relapse of PPCM Mortality Pregnancy outcome Pregnancy complication (gestational HT, pre-eclampsia, gestational DM, postpartum haemorrhage) Echocardiography parameter (LVEF decline) |
| De Souza et al 13 | 2001 | Retrospective cohort study | Brazil | 7 | Age: 15–28 (21.7±5.3) race: 3 white, 4 black | NYHA FC Echocardiography parameter (LVFS, LVID, LVIS, PWth, IVSTh) Pregnancy outcome Treatment |
| Douglass et al 19 | 2021 | Case control | USA | 37 | N/A | Relapse of PPCM Pregnancy outcome Treatment |
| Elkayam et al 20 | 2001 | Retrospective cohort study | USA | 44 | Age: 19–39 (29±6) race: 23 white, 16 black, 5 Hispanic | Mortality Pregnancy complication (pre-eclampsia, chronic HT) Pregnancy outcome Echocardiography parameter (mean LVEF) |
| Fett et al 17 | 2010 | Prospective cohort study | Haiti | 61 | N/A | NYHA FC Relapse of PPCM Mortality |
| Goland et al 10 | 2022 | Prospective cohort study | Israel | 75 | Age: 32.9±4.1 | Relapse of PPCM Pregnancy outcome Pregnancy complication (gestational HT/pre-eclampsia, gestational DM) Echocardiography parameter (LVEF) Treatment |
| Guldbrandt Hauge et al 18 | 2018 | Retrospective cohort study | Denmark | 16 | Age: 29.0±4.6 race: 12 white, 1 non-white | Relapse of PPCM Mortality Pregnancy outcome Pregnancy complication (gestational HT, postpartum haemorrhage) Treatment |
| Habli et al 27 | 2008 | Retrospective cohort study | USA | 37 | Age: G2 (28.1±6.3); G3 (27.3±8.1) race: G2 (5 white, 10 black, 1 Hispanic); G3 (10 white, 11 black) | Pregnancy outcome Echocardiography parameter (LVEF, LVED, LVES, fraction shortening) |
| Hilfiker-Kleiner et al 21 | 2017 | Prospective cohort study | Germany, Scotland and South Africa | 34 | Age: G1 (30±7); G2 (31±5) | Relapse of PPCM Mortality Pregnancy outcome Pregnancy complication (gestational HT) Echocardiography parameter (LVEF recovery) Treatment |
| Mandal et al 22 | 2011 | Retrospective cohort study | India | 6 | N/A | Mortality |
| Mishra et al 23 | 2006 | Prospective cohort study | India | 9 | N/A | NYHA FC Mortality Echocardiography parameter (LVEDD, LVESD, LVEF) |
| Moulig et al 28 | 2019 | Prospective cohort study | Germany | 17 | N/A | Pregnancy outcome Echocardiography parameter (LVEF) Treatment |
| Shani et al 24 | 2015 | Retrospective cohort study | Israel | 14 | N/A | Mortality Pregnancy outcome Pregnancy complication |
| Sinkey et al 39 | 2022 | Retrospective cohort study | England | 41 | Race: 22 white, 19 black | Echocardiography parameter (LVEF) |
| Sliwa et al 25 | 2004 | Prospective cohort study | South Africa | 6 | Age: 26–39 Race: 6 black | NYHA FC Mortality Pregnancy complication (none) Echocardiography parameter (LVEF decline) TNF-alpha |
| Witlin et al 40 | 1997 | Retrospective cohort study | USA | 7 | Age: 21–42 | Relapse of PPCM Echocardiography parameter (fractional shortening, LVIDd, LVIDs, LAD) |
| Yaméogo et al 26 | 2018 | Prospective cohort study | Brazil | 29 | Age: 26.7±4.6 race: 29 black | Mortality Pregnancy outcome Echocardiography parameter (LVEF, LVEDD, TAPSE, sPAP) |
HT, hypertension; IVSTh, intraventricular septum thickness; LAD, left atrial dimension; LVED, left ventricular end-diastolic dimensions; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; LVES, left ventricular end systolic dimensions; LVESD, left ventricular end-systolic diameter; LVFS, left ventricular fractional shortening; LVID, left ventricular end-diastolic internal dimension; LVIDd, left ventricular end-diastolic dimension; LVIDs, left ventricular end systolic dimension; LVIS, left ventricular end-systolic internal dimension; N/A, not available; NYHA FC, New York Heart Association functional class; PPCM, peripartum cardiomyopathy; PWth, left ventricular posterior wall thickness; sPAP, systolic pulmonary arterial pressure; SSP, subsequent pregnancy; TAPSE, tricuspid annular plan systolic excursion.
openhrt-2024-002626supp001.pdf (66.3KB, pdf)
Relapse of PPCM
Seven studies reported a relapse of PPCM after an SSP. Relapse was defined as a decrease of LVEF to 45% or less with or without symptoms of HF and/or a change in New York Heart Association (NYHA) functional classification in most of the studies. Among them, the relapse rate ranged from 5.3% to 29.5%.10 16–18 In a prospective cohort study with a relapse rate of 29.5% (18/61), recovered LV function defined by an LVEF≥55% before the SSP was associated with reduced risk for HF relapse in a post-PPCM pregnancy.17 However, 2 studies with a total of 15 relapses reported that all of the relapse cases had recovered LV function prior to the SSP,16 19 indicating that PPCM patients with fully recovered LV function also have a substantial risk for relapse in the SSP. A study by Douglass et al 19 found that HF medication does not guarantee to prevent a relapse of PPCM in recovered LV function patients. Exercise test echocardiography may be a potential tool to identify women with recovered LV function who have a lower risk of relapse, since nine women in an SSP who had adequate contractile reserve did not experience a relapse.17 Recovered LV function before an SSP could be a favourable prognostic factor, as all patients recovered normal LV function after their relapse.16 19
Mortality
The mortality rate is highly heterogeneous, ranging from 0% to 55.5%.10 14 16–18 20–26 Three studies with a total of 88 patients reported that none of the patients died during the SSP.10 16 18 Maternal age during SSP did not show significant correlation with the mortality rate. Persistent LV dysfunction (LVEF<50%) was associated with an increased mortality rate in the SSP (OR 13.17; 95% CI 1.54 to 112.28; p=0.02; I²=0%; figure 2). All patients who died during or after the SSP entered the SSP with persistent LV dysfunction or persistent cardiomyopathy, according to seven studies.14 16 17 21 22 24 25 However, a prospective cohort from Brazil reported there were no statistically significant differences between surviving and deceased women in terms of socioeconomic status, LV and right ventricular (RV) function before entering SSP. At the time of hospitalisation, congestive HF and lower LV and RV function were more frequently observed in women who died after pregnancy than in the group of surviving patients. The best predictor of maternal mortality based on the AUC was the LVEF at admission. With a sensitivity of 93% and a specificity of 87%, the optimal threshold value for predicting mortality during the initial SSP was an LVEF at admission of less than 40%.26 No mortality was reported in patients receiving bromocriptine on top of standard HF therapy (beta-blocker and angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB)), while two patients who died were only treated with standard HF therapy.21
Figure 2.
Forest plot of mortality in SSP with persistent LV dysfunction and PPCM. The individual OR is shown as a solid blue box, and the pooled estimate of OR is shown as a solid black diamond. Lines show the 95% CIs. LV, systolic diamet; M-H, Mantel-Haenszel; PPCM, peripartum cardiomyopathy; SSP, subsequent pregnancy.
Echocardiography parameters
In five studies, SSP was found to be significantly associated with a decrease in the mean of LVEF.10 20 21 23 26 A minor but significant decrease in LVEF was observed in a prospective cohort even at 1 and 6 months post partum, with the majority of these women having LVEF<55% prior to having SSP. Data from 34 SSPs showed that LVEF was statistically decreased at the third trimester (p=0.01) and early post partum (p=0.03).10 However, two studies reported there were no significant differences in LVEF after SSP.27 28 Persistent LV dysfunction (LVEF<50%) was associated with lower LVEF compared with patients with recovered LV function (MD −12.88; 95% CI −21.67 to −4.09; p=0.004; I²=64%; figure 3). The LV end-diastolic diameter (LVEDD) of PPCM women with SSP significantly increased, according to two prospective cohort studies involving a total of 38 SSPs.23 26 de Souza et al 13 reported a decrease in LV end systolic diameter (LVESD) after SSP (53±10–46±10 mm). However, a study from India had a different result, as LVESD was significantly increased during the worsening of symptoms (41±5–51.1±6 mm).23 Diastolic and RV functions remained unchanged before SSP and at follow-up.10 Patients receiving bromocriptine on top of standard HF therapy have a more favourable outcome at follow-up, as 62% of this group had full recovery of LV function compared with only 11% in patients with standard HF therapy.21
Figure 3.
Forest plot of LVEF in SSP with persistent LV dysfunction and PPCM. The individual mean difference is shown as a solid green box, and the pooled estimate of mean difference is shown as a solid black diamond. Lines show the 95% CIs. IV, inverse variance; LV, left ventricular; LVEF, left ventricular ejection fraction; PPCM, peripartum cardiomyopathy; SSP, subsequent pregnancy.
Pregnancy outcome and complications
Out of 365 SSPs, a total of 268 (73.4%) live birth children were observed. 34 (9.3%) pregnancies had spontaneous abortion, while the rest of them chose to terminate their pregnancies.10 13 14 16 18–21 24 26–28 Additionally, two SSP were classified as ectopic pregnancies, therefore, were also terminated.18 28 The majority of the SSP was observed alongside hypertension, which was present in 13.1% of patients (32/244).10 14 16 18 20 21 A prospective cohort from Brazil reported increased heart size in 7 out of 12 patients in which 1 of them also developed pre-eclampsia.14 Pre-eclampsia emerged as the predominant hypertensive complication in most studies, accounting for 50% of the total hypertension cases seen.10 14 16 20 Codsi et al 16 and Goland et al 10 both found three cases of gestational diabetes mellitus as one of the aggravating factors of the pregnancy. Postpartum haemorrhage was reported in three cases in a retrospective cohort.18 There were two documented SSP events, which were worsened by pulmonary congestions.24 In contrast to other studies, a study by Sliwa et al 25 in 2004 reported no pregnancy complications were seen in their study subjects.
Discussion
In this study, we evaluated the outcomes of SSP in women with PPCM. PPCM is an uncommon type of cardiomyopathy that arises in the later stages of pregnancy or early post partum. This potentially fatal disease is characterised by severe dysfunction of the LV and cardiac failure.1–3 29 Lack of reliable guidelines for individuals with previous PPCM on their SSP sets up an uncertainty for healthcare professionals, in which the present study attempts to address. Decisions about future pregnancies are complicated because women with PPCM have the potential for a diminished in LV function alongside possible relapse of PPCM, and even mortality. Consideration regarding the likelihood of relapse during or after an SSP is an essential element of management for women with PPCM. In most of the studies, relapse rate of PPCM in an SSP ranged from 5.3% to 29.5%.10 16–18 The condition of LV function before the SSP was associated with the risk of relapse for HF. Previous literature has shown that ventricular dysfunction recurs following the delivery of an SSP in the majority of PPCM patients, with a higher risk of undesirable consequences when LV function had not entirely recovered prior to the SSP.21 25
Recovered LV function before an SSP has the potential to be a beneficial prognostic factor since all patients recovered to normal LV function following their relapse. However, those with recovered LV function, still had a substantial chance of relapse in their SSP.16 19 Furthermore, even with a treatment of HF does not ensure that individuals with recovered LV function will not experience a relapse of PPCM.19 Based on our assessments, we suggest SSP should be avoided in both patients with persistent and recovered LV function due to the possibility of a relapse of PPCM. Considering women who had SSP that showed adequate contractile reserve in their exercise test echocardiography did not suffer a relapse, this test might be a viable method for identifying a probability of relapse in women with recovered LV function before SSP.17 Thus, further study in this particular field is required.
Women entering an SSP with a persistent LV dysfunction are at a significantly higher risk for mortality. Our study showed that patients with persistent LV dysfunction have a mortality rate 13.17 times higher than women with recovered LV function in their SSPs. With a sensitivity of 93% and specificity of 87%, the LVEF at admission was the best predictor of maternal death. The optimal threshold value for determining mortality during the SSP was an LVEF<40% at admission.26 Therefore, women with LVEF at admission <40% based on the echocardiography should be advised to terminate their pregnancy due to the increased risk of mortality. SSP was found to be significantly related to a decrease in LVEF.10 20 21 23 26 A decrease in LVEF was reported in both recovered and persistent LVEF conditions, even at 1 month and 6 months postpartum follow-up, in both surviving and non-surviving patients.10 26 LVEF was statistically decreased during the third trimester and early post partum.10 Our study observed that women with persistent LV dysfunction were associated with lower LVEF in their SSP compared with patients with recovered LV function. On the other hand, LVEDD has the potential to be an outcome predictor for women with SSP,30 as the increased LVEDD was found to be a significant predictor of persistent LV dysfunction, adverse outcomes and a lower probability of full recovery.31 Additionally, LVESD increased significantly as symptoms worsened.23 Higher level of LVESD was correlated with the lower LV function. The increased LVESD was an independent prognostic factors in predicting persistent LV dysfunction and PPCM recovery.32 33 Our study also observed that diastolic and RV functions remained unchanged before SSP and at follow-up. While pregnancy induces major alterations in haemodynamic that result in a significant increase in cardiac workload, recent studies have found that vascular dysfunction and cardiomyocyte apoptosis induced by late-gestational maternal hormones have been implicated as the primary causes of PPCM.29 34 This could be attributed to the higher likelihood of LV dysfunction occurring in PPCM as opposed to RV and diastolic dysfunction.
Patients receiving bromocriptine on top of standard HF therapy have a substantially improved outcome at follow-up. A study reported of a full recovery of LV function in 62% of patients with bromocriptine alongside standard HF therapy (beta-blocker and ACEi/ARB) in contrast to a mere 11% in patients receiving only standard HF therapy.21 There was no mortality in patients who received bromocriptine in addition to standard HF therapy, whereas two patients died with only standard HF therapy.21 The combination of these medications implies advantageous effects and might prevent relapse of PPCM if started promptly following post partum. Furthermore, according to a recent meta-analysis, adding bromocriptine to standard HF therapy in the PPCM group appeared to be correlated with considerably greater LVEF improvement as well as higher survival rate (91.6% vs 83.9%; RR=1.11; p=0.02; 95% CI 1.01 to 1.20).35
This study also observed maternal outcomes of 365 SSP with a total of 268 live birth children. A number of 9.3% of pregnancies had spontaneous abortion while the remaining of them decided to end their pregnancies.10 13 14 16 18–21 24 26–28 The likelihood of HF relapse has been highlighted as the justification for terminating the pregnancy. Some of patients had diminished LVEF prior to termination. On top of that, the substantial number of unintended SSPs and a higher prevalence of terminations in women with PPCM demonstrate that advice regarding contraception should be provided constantly, rather than only right afterwards PPCM diagnosis. Moreover, 13.1% of patients experienced SSP alongside hypertension. In most studies, pre-eclampsia emerged as the most common hypertensive complication, accounting for 50% of all hypertension cases seen.10 14 16 20 Hypertensive disorders in pregnancy, such as chronic hypertension, gestational hypertension, Hemolysis, Elevated Liver enzymes, Low Platelet (HELLP) syndrome and pre-eclampsia with or without eclampsia, present a significant high morbidity and mortality risk to both maternal and fetal.36 While hypertension tends to become a concern during pregnancy, the adverse effects of progression to pre-eclampsia/eclampsia are actually the primary concern. Further research showed that hypertension during pregnancy is linked to fetal growth restriction and placental abruption.37 Two studies10 16 discovered three cases of gestational diabetes mellitus as one of the pregnancy’s aggravating factors. Women with gestational diabetes mellitus increase the risk significantly of perinatal outcomes, such as pre-eclampsia, delivery at <37 weeks, primary caesarean delivery, shoulder dystocia or birth injury.38 Considering the unfavourable maternal and fetal outcomes of this condition, sterilisation might serve as a preventive measure for women with PPCM.
To the best of our knowledge, this is the first systematic review and meta-analysis of the outcomes of SSP in women with PPCM. We analysed the risk of relapse, mortality, echocardiography parameters, as well as pregnancy outcome and complications, to provide a comprehensive approach for considering the risk of further pregnancy after being diagnosed with PPCM. A substantial number of SSPs observed across diverse ethnic groups and individuals from various geographic regions is a major strength of our study, as it increases the generalisability of our findings to the attributes of the global population. Nevertheless, our study does have limitations. There were only two studies involved in the meta-analysis. Studies comparing recovered and persistent LV dysfunction patients were limited. Due to the scarcity of studies directly comparing the SSP group to the non-SSP group, we were unable to measure the pooled estimated risk of the SSP group. Therefore, further studies are required in order to estimate the risk of SSP compared with non-SSP in women with previous PPCM history.
Conclusion
Considerations related to SSP in women with a history of PPCM should be determined by the possibility of deteriorating LV function, relapse of PPCM and mortality. We advise preventing further pregnancy in both patients with persistent and recovered LV function regarding the likelihood of relapse in PPCM. Women entering SSP with persistent LV dysfunction have a mortality risk 13.17 times higher than women with recovered LV function. As a consequence, we strongly recommend that women with the LVEF<40% at admission should be advised to terminate their pregnancy. Bromocriptine, in addition to standard HF therapy, might be used in order to improve the outcome of patients and prevent mortality. Furthermore, SSP was also significantly associated with a decrease in LVEF, an increase in both LVEDD and LVESD, thus linked to the worsening of LV dysfunction.
Footnotes
Twitter: @muhanabejo
Contributors: MAW, MFI and RM contributed to the conception and design of the manuscript. MAW and GAL performed the literature searching, screening, data collection, data extraction and analysis. MAW, GAL, AAR, HAZ and SNH wrote the original draft, while MFI and RM revised the manuscript. MAW and RM are responsible for the overall content and serve as guarantors. All authors approved the final version of the manuscript.
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests: None declared.
Provenance and peer review: Not commissioned; externally peer reviewed.
Supplemental material: This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
Data availability statement
All data relevant to the study are included in the article or uploaded as online supplemental information.
Ethics statements
Patient consent for publication
Not applicable.
References
- 1. Bala R, Mehta S, Roy VC, et al. Peripartum cardiomyopathy: a review. Rev Port Cardiol 2023;42:917–24. 10.1016/j.repc.2023.01.029 [DOI] [PubMed] [Google Scholar]
- 2. Carlson S, Schultz J, Ramu B, et al. Peripartum cardiomyopathy: risks diagnosis and management. J Multidiscip Healthc 2023;16:1249–58. 10.2147/JMDH.S372747 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Morris VL, Mendoza C, Stevens GS, et al. Peripartum cardiomyopathy. J Educ Teach Emerg Med 2023;8:S1–34. 10.21980/J8ZS9M [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Nabbaale J, Okello E, Kibirige D, et al. Burden, predictors and short-term outcomes of peripartum cardiomyopathy in a black African cohort. PLoS One 2020;15:e0240837. 10.1371/journal.pone.0240837 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Gunderson EP, Croen LA, Chiang V, et al. Epidemiology of peripartum cardiomyopathy: incidence, predictors, and outcomes. Obstet Gynecol 2011;118:583–91. 10.1097/AOG.0b013e318229e6de [DOI] [PubMed] [Google Scholar]
- 6. Sliwa K, Petrie MC, van der Meer P, et al. Clinical presentation, management, and 6-month outcomes in women with peripartum cardiomyopathy: an ESC EORP registry. Eur Heart J 2020;41:3787–97. 10.1093/eurheartj/ehaa455 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Davis MB, Arany Z, McNamara DM, et al. Peripartum cardiomyopathy. J Am Coll Cardiol 2020;75:207–21. 10.1016/j.jacc.2019.11.014 [DOI] [PubMed] [Google Scholar]
- 8. Goland S, Modi K, Bitar F, et al. Clinical profile and predictors of complications in peripartum cardiomyopathy. J Card Fail 2009;15:645–50. 10.1016/j.cardfail.2009.03.008 [DOI] [PubMed] [Google Scholar]
- 9. Sliwa K, Petrie MC, Hilfiker-Kleiner D, et al. Long-term prognosis, subsequent pregnancy, contraception and overall management of peripartum cardiomyopathy: practical guidance paper from the heart failure association of the European society of cardiology study group on peripartum cardiomyopathy. Eur J Heart Fail 2018;20:951–62. 10.1002/ejhf.1178 [DOI] [PubMed] [Google Scholar]
- 10. Goland S, George J, Elkayam U, et al. Contemporary outcome of subsequent pregnancies in patients with previous peripartum cardiomyopathy. ESC Heart Fail 2022;9:4262–70. 10.1002/ehf2.14141 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Pachariyanon P, Bogabathina H, Jaisingh K, et al. Long-term outcomes of women with peripartum cardiomyopathy having subsequent pregnancies. J Am Coll Cardiol 2023;82:16–26. 10.1016/j.jacc.2023.04.043 [DOI] [PubMed] [Google Scholar]
- 12. Fett JD, Shah TP, McNamara DM. Why do some recovered peripartum cardiomyopathy mothers experience heart failure with a subsequent pregnancy Curr Treat Options Cardiovasc Med 2015;17:354. 10.1007/s11936-014-0354-x [DOI] [PubMed] [Google Scholar]
- 13. de Souza JL, de Carvalho Frimm C, Nastari L, et al. Left ventricular function after a new pregnancy in patients with Peripartum cardiomyopathy. J Card Fail 2001;7:30–5. 10.1054/jcaf.2001.22424 [DOI] [PubMed] [Google Scholar]
- 14. Albanesi Filho FM, da Silva TT. Natural course of subsequent pregnancy after peripartum cardiomyopathy. Arq Bras Cardiol 1999;73:47–57. [PubMed] [Google Scholar]
- 15. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. 10.1136/bmj.n71 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Codsi E, Rose CH, Blauwet LA. Subsequent pregnancy outcomes in patients with peripartum cardiomyopathy. Obstet Gynecol 2018;131:322–7. 10.1097/AOG.0000000000002439 [DOI] [PubMed] [Google Scholar]
- 17. Fett JD, Fristoe KL, Welsh SN. Risk of heart failure relapse in subsequent pregnancy among peripartum cardiomyopathy mothers. Int J Gynaecol Obstet 2010;109:34–6. 10.1016/j.ijgo.2009.10.011 [DOI] [PubMed] [Google Scholar]
- 18. Guldbrandt Hauge M, Johansen M, Vejlstrup N, et al. Subsequent reproductive outcome among women with peripartum cardiomyopathy: a nationwide study. BJOG 2018;125:1018–25. 10.1111/1471-0528.15046 [DOI] [PubMed] [Google Scholar]
- 19. Douglass EJ, Cooper LT, Morales-Lara AC, et al. A case-control study of peripartum cardiomyopathy using the rochester epidemiology project. J Card Fail 2021;27:132–42. 10.1016/j.cardfail.2020.12.021 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Elkayam U, Tummala PP, Rao K, et al. Maternal and fetal outcomes of subsequent pregnancies in women with peripartum cardiomyopathy. N Engl J Med 2001;344:1567–71. 10.1056/NEJM200105243442101 [DOI] [PubMed] [Google Scholar]
- 21. Hilfiker-Kleiner D, Haghikia A, Masuko D, et al. Outcome of subsequent pregnancies in patients with a history of peripartum cardiomyopathy. Eur J Heart Fail 2017;19:1723–8. 10.1002/ejhf.808 [DOI] [PubMed] [Google Scholar]
- 22. Mandal D, Mandal S, Mukherjee D, et al. Pregnancy and subsequent pregnancy outcomes in peripartum cardiomyopathy. J Obstet Gynaecol Res 2011;37:222–7. 10.1111/j.1447-0756.2010.01378.x [DOI] [PubMed] [Google Scholar]
- 23. Mishra TK, Swain S, Routray SN. Peripartum cardiomyopathy. Int J Gynaecol Obstet 2006;95:104–9. 10.1016/j.ijgo.2006.06.013 [DOI] [PubMed] [Google Scholar]
- 24. Shani H, Kuperstein R, Berlin A, et al. Peripartum cardiomyopathy - risk factors, characteristics and long-term follow-up. J Perinat Med 2015;43:95–101. 10.1515/jpm-2014-0086 [DOI] [PubMed] [Google Scholar]
- 25. Sliwa K, Forster O, Zhanje F, et al. Outcome of subsequent pregnancy in patients with documented peripartum cardiomyopathy. Am J Cardiol 2004;93:1441–3, . 10.1016/j.amjcard.2004.02.053 [DOI] [PubMed] [Google Scholar]
- 26. Yaméogo NV, Samadoulougou AK, Kagambèga LJ, et al. Maternal and fetal prognosis of subsequent pregnancy in black African women with peripartum cardiomyopathy. BMC Cardiovasc Disord 2018;18:119. 10.1186/s12872-018-0856-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. Habli M, O’Brien T, Nowack E, et al. Peripartum cardiomyopathy: Prognostic factors for long-term maternal outcome. Am J Obstet Gynecol 2008;199:415. 10.1016/j.ajog.2008.06.087 [DOI] [PubMed] [Google Scholar]
- 28. Moulig V, Pfeffer TJ, Ricke-Hoch M, et al. Long-term follow-up in peripartum cardiomyopathy patients with contemporary treatment: low mortality, high cardiac recovery, but significant cardiovascular co-morbidities. Eur J Heart Fail 2019;21:1534–42. 10.1002/ejhf.1624 [DOI] [PubMed] [Google Scholar]
- 29. Wijayanto MA, Lukas GA, Greatalya LAD, et al. Global research trends and future direction in peripartum cardiomyopathy: a bibliometric analysis. Acta Inform Med 2023;31:270–4. 10.5455/aim.2023.31.270-274 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Iorgoveanu C, Zaghloul A, Ashwath M. Peripartum cardiomyopathy: a review. Heart Fail Rev 2021;26:1287–96. 10.1007/s10741-020-10061-x [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Tak BT, Cay S, Pamukcu HE, et al. Prognostic nutritional index as a novel marker for prediction of prognosis in patients with peripartum cardiomyopathy. Medicine (Baltimore) 2020;99:e19524. 10.1097/MD.0000000000019524 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Gürkan U, Akgöz H, Aksoy Ş, et al. Value of the neutrophil-to-lymphocyte ratio in predicting left ventricular recovery in patients with peripartum cardiomyopathy. Wien Klin Wochenschr 2017;129:893–9. 10.1007/s00508-017-1227-6 [DOI] [PubMed] [Google Scholar]
- 33. Hosseinpour A, Hosseinpour H, Kheshti F, et al. Prognostic value of various markers in recovery from peripartum cardiomyopathy: a systematic review and meta-analysis. ESC Heart Fail 2022;9:3483–95. 10.1002/ehf2.14085 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34. Arany Z, Elkayam U. Peripartum cardiomyopathy. Circulation 2016;133:1397–409. 10.1161/CIRCULATIONAHA.115.020491 [DOI] [PubMed] [Google Scholar]
- 35. Trongtorsak A, Kittipibul V, Mahabir S, et al. Effects of bromocriptine in peripartum cardiomyopathy: a systematic review and meta-analysis. Heart Fail Rev 2022;27:533–43. 10.1007/s10741-021-10185-8 [DOI] [PubMed] [Google Scholar]
- 36. Spiro L, Scemons D. Management of chronic and gestational hypertension of pregnancy: a guide for primary care nurse practitioners. Open Nurs J 2018;12:180–3. 10.2174/1874434601812010180 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Hauspurg A, Sutton EF, Catov JM, et al. Aspirin effect on adverse pregnancy outcomes associated with stage 1 hypertension in a high-risk cohort. Hypertension 2018;72:202–7. 10.1161/HYPERTENSIONAHA.118.11196 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38. Buchanan TA, Xiang AH, Page KA. Gestational diabetes mellitus: risks and management during and after pregnancy. Nat Rev Endocrinol 2012;8:639–49. 10.1038/nrendo.2012.96 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39. Sinkey RG, Rajapreyar IN, Szychowski JM, et al. Racial disparities in peripartum cardiomyopathy: eighteen years of observations. J Matern Fetal Neonatal Med 2022;35:1891–8. 10.1080/14767058.2020.1773784 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40. Witlin AG, Mabie WC, Sibai BM. Peripartum cardiomyopathy: an ominous diagnosis. Am J Obstet Gynecol 1997;176:182–8. 10.1016/s0002-9378(97)80033-6 [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
openhrt-2024-002626supp001.pdf (66.3KB, pdf)
Data Availability Statement
All data relevant to the study are included in the article or uploaded as online supplemental information.


