Coverage of highly active antiretroviral therapy among postpartum women in Malawi

The expanding services of antiretroviral treatment (ART) in sub-Saharan Africa provide unique opportunities to reduce HIV/AIDS-related morbidity and mortality. In these settings, HIV prevalence among antenatal women remains high and treating eligible pregnant or breastfeeding women with antiretrovirals can substantially reduce transmission of HIV from the mother to her infant. However, identification of women eligible for treatment and ensuring access to ART services is challenging. In this analysis, we used data from a large clinical trial (the PEPI-Malawi study, 2004-09) to prevent mother-to-child transmission of HIV through extended antiretroviral prophylaxis of infants to examine barriers for wider coverage with highly active antiretroviral treatment (HAART) of postpartum women. Maternal HAART was not part of the original PEPI-Malawi clinical trial but became available through a government programme during the course of the study. Therefore, eligible women (CD4 cell count <250) who participated in the PEPI-Malawi trial were counselled and referred to the government ART clinics to initiate HAART. Of 3335 women who enrolled in the PEPI-Malawi study, 803 (24%) were eligible for HAART based on CD4 cell count. The proportion of women newly initiating HAART at the ART clinic remained low and constant (<20%) throughout the study period. However, the cumulative proportion of women receiving HAART increased substantially over time (29% in 2005 to 69% in 2009). Similarly, counselling and referral of eligible women substantially increased and became 100% during the last two years. There were no statistically significant differences in characteristics of eligible women who received or did not receive HAART postpartum. Despite limitations of not being able to obtain detailed data, the main barriers appeared to be related to the health-care system delivery of ART services. Issues of physical space, more personnel and better delivery need to be addressed to increase access to HAART in these settings.     

Effectiveness of antiretroviral treatment in a South African program: a cohort study

BACKGROUND: The effectiveness of the South African government's expanding antiretroviral treatment program is unknown. Observational studies of treatment effectiveness are prone to selection bias, rarely compare patients receiving antiretroviral treatment with similar patients not receiving antiretroviral treatment, and underestimate mortality rates unless patients are actively followed up. METHODS: We followed up 14 267 patients in the Public Sector Anti-Retroviral Treatment project in Free State, South Africa, for up to 20 months after enrollment. A total of 3619 patients received highly active triple antiretroviral treatment (HAART) for up to 19 months (median, 6 months; interquartile range, 3-9 months) after enrollment. Patients' clinical data were linked with the national mortality register. Marginal structural regression models adjusted for baseline and time-varying covariates. RESULTS: Of 4570 patients followed up for at least 1 year, 53.2% died. Eighty-seven percent of patients who died had not received HAART. HAART was associated with lower mortality (hazard ratio, 0.14; 95% confidence interval [CI], 0.11-0.18) and with the presence of tuberculosis (hazard ratio, 0.61; 95% CI, 0.46-0.81) after adjusting for age, sex, weight, clinic, district, CD4 cell count, cotrimoxazole therapy, tuberculosis at baseline, and previous antiretroviral therapy. Cotrimoxazole therapy was associated with lower mortality (hazard ratio, 0.37; 95% CI, 0.32-0.42). Each month of HAART was associated with an increase in CD4 cell count of 15.1 cells/microL (95% CI, 14.7-15.5 cells/microL) and with an increase in body weight of 602 g (95% CI, 548-658 g). CONCLUSIONS: HAART provided through these South African government health services seems as effective as that provided in high-income countries. Delays starting HAART contributed to high mortality rates. Faster expansion and timely commencement of HAART are needed.     

Low mortality risk but high loss to follow‐up among patients in the Tanzanian national HIV care and treatment programme

Objective To analyse survival and retention rates of the Tanzanian care and treatment programme. Methods Routine patient‐level data were available from 101 of 909 clinics. Kaplan–Meier probabilities of mortality and attrition after ART initiation were calculated. Mortality risks were corrected for biases from loss to follow‐up using Egger’s nomogram. Smoothed hazard rates showed mortality and attrition peaks. Cox regression identified factors associated with death and attrition. Median CD4 counts were calculated at 6 month intervals. Results In 88,875 adults, 18% were lost to follow up 12 months after treatment initiation, and 36% after 36 months. Cumulative mortality reached 10% by 12 months (15% after correcting for loss to follow‐up) and 14% by 36 months. Mortality and attrition rates both peaked within the first six months, and were higher among males, those under 45 kg and those with CD4 counts below 50 cells/μl at ART initiation. In the first year on ART, median CD4 count increased by 126 cells/μl, with similar changes in both sexes. Conclusion Earlier diagnoses through expanded HIV testing may reduce high mortality and attrition rates if combined with better patient tracing systems. Further research is needed to explore reasons for attrition.     

Highly active antiretroviral therapy and cervical intraepithelial neoplasia

Highly active antiretroviral therapy (HAART) has improved HIV prognosis, but its effect on cervical intraepithelial neoplasia (CIN), which is associated with HIV, is uncertain. Among 71 HAART-treated women the prevalence of CIN before HAART was 55%. After a median of 10 months after starting HAART the prevalence had increased to 62% (P = 0.20); 13% of patients experienced regression of a CIN lesion, and this was most strongly associated with a greater increase in CD4 cell count. Such studies will provide the basis for guidelines for monitoring CIN in HIV-positive women in the HAART era.     

Breastfeeding and maternal HIV-1 disease progression and mortality

OBJECTIVE: To examine the association between breastfeeding and disease progression among HIV-infected women in Dar es Salaam, Tanzania. DESIGN AND METHODS: Cohort study design with Cox proportional hazards models. RESULTS: The relative risk of death comparing women who recently had been breastfeeding to those who were not breastfeeding was 0.47 (95% confidence interval, 0.18-1.20). Neither breastfeeding status nor the duration of exclusive or partial breastfeeding was associated with HIV-1 disease progression, represented by death or development of a low CD4 cell count, anemia or excessive weight loss, in multivariate analyses. These associations remained insignificant when women with relatively low and high CD4 cell counts were analyzed separately. CONCLUSION: There is insufficient evidence to support the hypothesis that breastfeeding is detrimental to the health of HIV-infected women.     

Anemia in human immunodeficiency virus-infected and uninfected women in Rwanda

To determine the prevalence and risk factors of anemia among human immunodeficiency virus (HIV)-infected women in Rwanda and the influence of highly active antiretroviral therapy (HAART) on anemia, we analyzed 200 HIV-positive women and 50 HIV-negative women in a cross-sectional study. Clinical examinations and iron and vitamin B(12) assays were performed, and complete blood counts, serum folic acid levels, and CD4 cell count determined. The prevalence of anemia was significantly higher among HIV-positive women (29%) than among HIV-negative women (8%) (P < 0.001). Risk factors for anemia were lower body mass index (odds ratio [OR] = 3.4, 95% confidence interval [CI] = 2.4-4.1), zidovudine use (OR = 1.14, 95% CI = 1.01-1.29), lack of HAART (OR = 1.44, 95% CI = 1.21-1.67), oral candidiasis (OR = 1.4, 95% CI = 1.2-1.6), pulmonary tuberculosis (OR = 1.8, 95% CI = 1.7-2.2), cryptococcal meningitis (OR = 1.6, 95% CI = 1.21-1.8), Pneumocystis jiroveci pneumonia (OR = 1.41, 95% CI = 1.20-1.65) and CD4 lymphocyte count < 200 cells/μL (OR = 2.41, 95% CI = 2.01-3.07). The mean ± SD hemoglobin level of 10.9 ± 1.6 g/dL at HAART initiation significantly increased to 12.3 ± 1.5 g/dL in 8 months (P < 0.001). Anemia increases with HIV stage, and HAART is associated with a significant improvement in hemoglobin levels.     

Immunologic response to highly active antiretroviral therapy and mortality reduction in a cohort of human immunodeficiency virus-positive persons in Mozambique

Since February 2002, the Drug Resources Enhancement against AIDS and Malnutrition Program has provided highly active antiretroviral therapy (HAART) and immunologic and virologic monitoring free of charge. We conducted a cohort study of persons infected with human immunodeficiency virus in Mozambique. Only persons treated with HAART with available CD4 cell counts at baseline and ≥ 1 CD4 cell count after HAART were included. Survival analysis was applied to evaluate the prognostic value of CD4 cell counts measured at three months. Possible confounders were considered. A total of 753 persons who started HAART included; 59% were females. Median age was 34 years (range = 16-67 years), and the median CD4 cell count at baseline was 172 cells/mm3 (interquartile range = 87-261 cells/mm3, range = 0-1,322 cells/mm3). Overall, 105 persons (14%) died. Of these persons 54 (51%) developed AIDS before they died; 25 (3%) died during the first three months. After three months of therapy, the individual median CD4 cell count change from the baseline value was +101 cells/mm3 (interquartile range = +27 to +187 cells/mm3, range = -723 to +310 cells/mm3). A median CD4 increment of 100 cells/mm3 in three months was associated with a mortality reduction of 50% compared with an increase of < 50 cells (relative hazard of death adjusted for baseline CD4 cell count = 0.54, 95% confidence interval = 0.30-0.95). A good initial response to HAART was associated with a significant reduction of mortality. This finding supports the effectiveness of HAART in resource-poor settings.     

Randomized trial of vitamin supplements in relation to transmission of HIV-1 through breastfeeding and early child mortality

BACKGROUND: HIV-1 transmission through breastfeeding is a global problem and has been associated with poor maternal micronutrient status. METHODS: A total of 1078 HIV-infected pregnant women from Tanzania were randomly assigned to vitamin A or multivitamins excluding A from approximately 20 weeks' gestation and throughout lactation. RESULTS: Multivitamins excluding A had no effect on the total risk of HIV-1 transmission (RR 1.04, 95% CI 0.82-1.32, P= 0.76). Vitamin A increased the risk of transmission (RR 1.38, 95% CI 1.09-1.76, P = 0.009). Multivitamins were associated with non-statistically significant reductions in transmission through breastfeeding, and mortality by 24 months among those alive and not infected at 6 weeks. Multivitamins significantly reduced breastfeeding transmission in infants of mothers with low baseline lymphocyte counts (RR 0.37; 95% CI 0.16-0.85, P = 0.02) compared with infants of mothers with higher counts (RR 0.99, 95% CI 0.68-1.45, P = 0.97; -for-interaction 0.03). Multivitamins also protected against transmission among mothers with a high erythrocyte sedimentation rate (P-for-interaction 0.06), low hemoglobin (P-for-interaction 0.06), and low birthweight babies (P-for-interaction 0.04). Multivitamins reduced death and prolonged HIV-free survival significantly among children born to women with low maternal immunological or nutritional status. Vitamin A alone increased breastfeeding transmission but had no effect on mortality by 24 months. CONCLUSION: Vitamin A increased the risk of HIV-1 transmission. Multivitamin (B, C, and E) supplementation of breastfeeding mothers reduced child mortality and HIV-1 transmission through breastfeeding among immunologically and nutritionally compromised women. The provision of these supplements to HIV-infected lactating women should be considered.     

Initiation of highly active antiretroviral therapy among pregnant women in Cape Town,South Africa

Objective To investigate highly active antiretroviral therapy (HAART) initiation among pregnant women and the optimum model of service delivery for integrating HAART services into antenatal care. Methods We analysed clinic records to reconstruct a cohort of all HIV‐infected pregnant women eligible for HAART at four antenatal clinics representing three service delivery models in Cape Town, South Africa. To assess HAART coverage, records of women determined to be eligible for HAART in pregnancy were reviewed at corresponding HIV treatment services. Results Of 13 208 pregnant women tested for HIV, 26% were HIV‐infected and 15% were HAART‐eligible based on a CD4 cell count of ≤ 200 cells/μl. Among eligible women, 51% initiated HAART before delivery, 27% received another prevention of mother‐to‐child transmission (PMTCT) intervention and 22% did not receive any antiretroviral intervention before delivery. The proportions of women initiating HAART between the different service delivery models were comparable. The median gestational age at first presentation was 26 weeks, and early gestational age at first presentation was the strongest predictor of being on HAART by delivery. Of the women who did not initiate HAART in pregnancy, 24% started treatment within 2 years postpartum. Conclusions In this setting with clear PMTCT and HAART protocols, services failed to prioritize and initiate a high proportion of eligible pregnant women on HAART. The initiation of HAART in pregnancy requires strengthened antenatal and HIV services that target women with advanced stage disease.     

Do gender differences in CD4 cell counts matter?

OBJECTIVE: To examine the effect of gender on disease progression and whether gender differences in CD4 lymphocyte counts persisted for the entire course from HIV seroconversion until (death from) AIDS. METHODS: CD4 lymphocyte counts were modelled in 221 female and 443 male seroconverters following seroconversion, backwards from AIDS and backwards from death using regression analysis for repeated measurements. RESULTS: In the period before use of highly active antiretroviral therapy (HAART), progression to AIDS and to death were marginally slower in women than in men as assessed by proportional hazards analysis. Women seroconverted for HIV, developed AIDS and died at higher CD4 cell counts than men (women: 815, 146 and 44 x 10(6) cells/l, respectively; men: 727, 49 and 22 x 10(6) cells/l, respectively), although differences were only statistically significant at AIDS onset. Declines in CD4 lymphocyte counts were not significantly affected by gender and absolute differences between men and women were stable, with exception for the trajectory close to AIDS when the decline became steeper for men than women. CONCLUSION: These gender differences in CD4 lymphocyte counts suggest a delay of initiation of therapy in women compared with men (our model predicted that women reach the threshold of starting HAART at about 12 months later than men). If this delay unfavourably influences progression, treatment guidelines should be revised so that women can benefit equally from HAART.     

Survey of lactation suppression in HIV-positive pregnant women

The risk of HIV transmission via breastfeeding is well reported. We conducted a national survey in the UK to look at the current knowledge and postpartum practice of HIV physicians caring for HIV-positive pregnant women. In total, 167 questionnaires were distributed, 85 (51%) questionnaires were returned. All the respondents advised their patients against breastfeeding, 17 (23%) respondents routinely prescribed drugs for postpartum lactation suppression and 32 (43%) detailed awareness of interactions between antiretroviral therapy and dopaminergic lactation suppression agents. Thirteen respondents reported awareness of guidance on lactation suppression. The knowledge and use of lactation suppression agents appears to be low. However, its use will not only reduce postnatal mastitis and breast engorgement but will also help women deal with social pressures to breastfeed. Increased use in specific circumstances will improve the postnatal care of HIV-positive pregnant women in the UK.     

Excessive early mortality in the first year of treatment in HIV type 1-infected patients initiating antiretroviral therapy in resource-limited settings

The response to treatment and risk factors for early mortality following initiation of combination antiretrovirals(ARVs) in a cohort of African patients are described in a retrospective cohort design. Medical history, laboratory parameters, and mortality data were reviewed for patients initiating ARVs in 12 clinical centers in Mozambique, Tanzania, and Malawi. Among 3456 HIV-1-infected patients who received ARVs for more than 6 months, at baseline 72% had WHO clinical stages 3/4, 7% had a viral load 400 copies/ml, and 38% had a CD4 cell count >200/microl. One year later, 78% had undetectable virus loads and 79% had CD4 cell counts >200 cells/mm3. In the first year of HAART 260 deaths occurred (97 per 1000 person/years) with mortality peaking in the first 3 months. The highest mortality was observed in patients with low BMI, low hemoglobin levels, and CD4 values <200 cells/microl at baseline. Mortality rates following initiation of HAART are higher in patients in resource-limited areas, particularly in the first 90 days following treatment initiation.HAART initiated at higher CD4 cell count levels, especially among malnourished and/or anemic patients, will carry significant public health impact.     

Prevalence and predictors of HIV-associated weight loss in the era of highly active antiretroviral therapy

This study was a cross-sectional study of 122 HIV-positive subjects to determine the prevalence and predictors of weight loss in the era of highly active antiretroviral therapy (HAART). Forty per cent reported lipodystrophy, 40% had documented weight loss (mean 6.6 kg). Mean intake 13,400 kJ (118% of estimated requirements calculated using the Harris-Benedict equation). One hundred (82%) were taking antiretroviral therapy. Using forward stepwise logistic regression analysis only viral load (VL) was significantly associated with weight loss when intake, CD4 T-cell count, lipodystrophy, and age were entered into the model with VL (log copies/mL). Every one log increase in HIV VL was associated with an odds of weight loss of 1.58 (P=0.0008). Weight loss is still common in the HAART era. HIV VL was the most significant predictor of weight loss in this sample. Inadequate dietary intake and self-reported lipodystrophy were not related to weight loss in this population.     

Anal intraepithelial neoplasia in the highly active antiretroviral therapy era among HIV-positive men who have sex with men

OBJECTIVES: The incidence of anal cancer among men who have sex with men (MSM) has continued to increase since the introduction of highly active antiretroviral therapy (HAART). The prevalence of the putative anal cancer precursor, anal intraepithelial neoplasia (AIN) was high among HIV-positive MSM prior to the availability of HAART but little is known about AIN since HAART was introduced. We characterized the prevalence of AIN among HIV-positive MSM and examined the association between AIN and various factors including use of HAART. DESIGN AND METHODS: A baseline point-prevalence analyses in a prospective cohort study of AIN was performed at a university-based research clinic. A total of 357 HIV-positive MSM with no history of anal cancer completed a questionnaire detailing behaviors and medical history, anal cytology and human papillomavirus (HPV) testing, and high-resolution anoscopy with biopsy for detection of AIN. RESULTS: Eighty-one percent of participants with available CD4+ cell counts at baseline had AIN of any grade; 52% had AIN 2 or 3; and 95% had anal HPV infection. In multivariate analysis, detection of > or = 6 HPV types [odds ratio (OR), 36; 95% confidence interval (CI), 7.4-171) and use of HAART (OR, 10; 95% CI, 2.6-38) were associated with AIN after adjustment for length of time participants were HIV-positive, CD4+ cell count and HIV viral load. CONCLUSIONS: The prevalence of AIN has remained high among HIV-positive MSM after the introduction of HAART. Our data indicate that HAART is not associated with a reduced prevalence of AIN and support measures to prevent anal cancer among HIV-positive MSM whether or not they are using HAART.     

Deaths in the era of HAART: contribution of late presentation, treatment exposure, resistance and abnormal laboratory markers

OBJECTIVES: To describe the characteristics of deaths that occur among HIV-positive individuals in the HAART era. DESIGN: Observational database. METHODS: Deaths were reviewed that occurred among HIV-positive individuals seen at the Royal Free Hospital, London between January 1998 and December 2003. RESULTS: Over the study period, there were 121 deaths; death rates declined from approximately 2.0/100 person-years of follow-up in 1998-2000 to approximately 1.0/100 person-years of follow-up in 2001-2003. Approximately one half of deaths (45.5%) were from AIDS-related causes and 74 deaths (61.2%) occurred in individuals who had received HAART: patients had been exposed to a median of seven (range 2-14) antiretroviral drugs and two-fifths had started treatment in the pre-HAART era. Another 15 patients had received only non-HAART treatment regimens prior to death. The median pre-death CD4 cell counts were 68 and 167 cells/microl among those who had and had not received HAART; 23 (31.1%) and 4 (8.5%) had HIV RNA < 400 copies/ml, respectively. Of the patients exposed to HAART for at least 6 months and who experienced viral rebound, information was available on resistance for 26 (21.5% of the total deaths) and 19 of those tested had at least one resistance mutation (median 5, range, 1-16). CONCLUSIONS: While mortality rates among HIV-infected individuals at our centre have fallen since 1988, the deaths that do now occur are more diverse and are the result of a number of factors, including late presentation, delayed uptake of HAART and the previous use of treatment combinations that are now viewed as suboptimal.     

“I did not feel like a mother”: The success and remaining challenges to exclusive formula feeding among HIV-positive women in Brazil

Exclusive and safe formula feeding can eliminate the risk of vertical HIV transmission due to breastfeeding. Therefore, many countries advise all HIV-positive women to avoid breastfeeding their infants. However, little research explores the experiences of women attempting to exclusively formula feed in countries with free and universal access to highly active antiretroviral therapy (HAART). This article examines the success of Brazil in supporting HIV-positive women as engage in exclusive formula feeding (EFF). We conducted in-depth interviews with 30 HIV-positive women receiving care at the primary facility for HIV/AIDS in Salvador, Brazil about their attitudes and practices related to EFF as well as challenges with adhering to EFF. All interviews were recorded, professionally transcribed and translated, and then analyzed. Our results showed that one woman reported both breastfeeding and formula feeding her infant; all others reported EFF. Postpartum counseling regarding the risk of HIV transmission through breastfeeding was the primary motivation for EFF. Challenges included difficulty reconciling their perceptions that breastfeeding is an important maternal responsibility, trouble accepting that breastfeeding can cause potential to harm their infants, confronting HIV-related stigma associated with EFF, and unexpected financial burdens due to EFF. We conclude that HIV-positive women adhered to national guidelines recommending EFF; this phenomenon has likely contributed to declining rates of vertical transmission in Brazil. Despite this success, many women experienced challenges with EFF. Greater support services may enhance Brazil's success in empowering HIV-positive women and eliminating vertical HIV transmission via breastfeeding.     

Perinatal transmission of HIV-1: lack of impact of maternal HIV infection on characteristics of livebirths and on neonatal mortality in Kigali, Rwanda

We present the baseline results of a prospective cohort study on the perinatal transmission of HIV-1 in Kigali, Rwanda. HIV-1-antibody testing was offered to all women of urban origin delivering a live newborn at the maternity ward of the Centre Hospitalier de Kigali from November 1988 to June 1989; 218 newborns of 215 HIV-positive mothers were matched to 218 newborns of 216 HIV-negative mothers. The matching criteria were maternal age and parity. No differences in socioeconomic characteristics were observed between HIV-positive and HIV-negative women. HIV-positive mothers more frequently reported a history of at least one death of a previously born child (P less than 0.01) and a history of abortion (P less than 0.001). Most of the HIV-positive women were asymptomatic, but 72.4% of them had a CD4; CD8 ratio less than 1 versus 10.1% in the HIV-negative group (P less than 0.001). The frequency of signs and symptoms was not statistically different in the two groups, except for a history of herpes zoster or chronic cough, which was more frequent among HIV-positive women. The rates of prematurity, low birth weight, congenital malformations and neonatal mortality were comparable in the two groups. However, infants of HIV-positive mothers had a mean birth weight 130 g lower than the infants of HIV-negative mothers (P less than 0.01). The impact of maternal HIV-1 infection on the infant seems limited during the neonatal period.     

Response to highly active antiretroviral therapy among severely immuno-compromised HIV-infected patients in Cambodia

BACKGROUND: HAART efficacy was evaluated in a real-life setting in Phnom Penh (Médecins Sans Frontières programme) among severely immuno-compromised patients. METHODS: Factors associated with mortality and immune reconstitution were identified using Cox proportional hazards and logistic regression models, respectively. RESULTS: From July 2001 to April 2005, 1735 patients initiated HAART, with median CD4 cell count of 20 (inter-quartile range, 6-78) cells/microl. Mortality at 2 years increased as the CD4 cell count at HAART initiation decreased, (4.4, 4.5, 7.5 and 24.7% in patients with CD4 cell count > 100, 51-100, 21-50 and < or = 20 cells/microl, respectively; P < 10). Cotrimoxazole and fluconazole prophylaxis were protective against mortality as long as CD4 cell counts remained < or = 200 and < or = 100 cells/microl, respectively. The proportion of patients with successful immune reconstitution (CD4 cell gain > 100 cells/microl at 6 months) was 46.3%; it was lower in patients with previous ART exposure [odds ratio (OR), 0.16; 95% confidence interval (CI), 0.05-0.45] and patients developing a new opportunistic infection/immune reconstitution infection syndromes (OR, 0.71; 95% CI, 0.52-0.98). Similar efficacy was found between the stavudine-lamivudine-nevirapine fixed dose combination and the combination stavudine-lamivudine-efavirenz in terms of mortality and successful immune reconstitution. No surrogate markers for CD4 cell change could be identified among total lymphocyte count, haemoglobin, weight and body mass index. CONCLUSION: Although CD4 cell count-stratified mortality rates were similar to those observed in industrialized countries for patients with CD4 cell count > 50 cells/microl, patients with CD4 cell count < or = 20 cells/microl posed a real challenge to clinicians. Widespread voluntary HIV testing and counselling should be encouraged to allow HAART initiation before the development of severe immuno-suppression.     

Effect of pre-eclampsia-eclampsia on major cardiovascular events among peripartum women in Taiwan

There is no large-scale population-based study to clarify the association between major adverse cardiovascular events (MACEs) and pre-eclampsia/eclampsia. A population-based Taiwanese cohort study was performed in 1,132,064 parturients from 1999 to 2003 using a dataset linking birth certificates and National Health Insurance hospital discharge data. Sociodemographic factors and obstetric complications were used in multivariate logistic regression models to determine adjusted hazard ratios of pre-eclampsia/eclampsia on risks of MACEs and mortality during pregnancy to at least the third year postpartum. Incidence rates of MACEs and all maternal mortality in women with pre-eclampsia/eclampsia were 16.21 and 40.38 per 100,000 patients per year, respectively. Women with pre-eclampsia/eclampsia had a 13.0-fold higher incidence of myocardial infarction, a 8.3-fold higher incidence of heart failure, a 14.5-fold higher incidence of stroke, a 12.6-fold higher incidence of MACEs, a 7.3-fold higher incidence of MACEs without stroke, a 2.3-fold higher incidence of MACE-related deaths, and a 6.4-fold higher incidence of overall death than women without pre-eclampsia/eclampsia. Kaplan-Meier survival curve discriminated in MACEs, nonstroke MACEs, MACE related death and overall death. In conclusion, women with pre-eclampsia/eclampsia have a significantly higher risk of MACEs, especially myocardial infarction and stroke, during pregnancy and their risk remains significant to ≥36 months postpartum. Our results suggest that women with pre-eclampsia/eclampsia should be closely monitored during pregnancy and for up to ≥3 years postpartum.