Maternal deaths due to indirect causes: Report from a tertiary care center of a developing country

Abstract

Objective

To assess the causes of indirect maternal deaths.

Setting

The Department of Obstetrics & Gynecology, of a tertiary referral center in Karachi, Pakistan, from January 2018 to December 2020. Maternal deaths were categorized according to World Health Organization guidelines into direct and indirect deaths.

Result

The total maternal deaths during the study period were 96, with 26 (27%) due to indirect causes. The mean age in the indirect group was 27 (range: 20–35) years, with only eight (31%) registered (attending for three of more antenatal visits). The mean gestational age was 33 (range: 22–39) weeks. Cesarean section was the main mode of delivery, in 13 (50%). Perinatal mortality was 68%. Cardiac and hepatic diseases (each six deaths, 23%) were the main causes of indirect maternal deaths. The majority of women (20; 76%) died during the postpartum period. Delays in seeking medical help, referral, and appropriate treatment were observed in 10, 9, and 7 cases, respectively.

Conclusion

Indirect maternal deaths are an important cause of maternal mortality.

Keywords

Maternal mortality indirect maternal death cardiac disease hepatic disease

Introduction

A maternal death is defined as the “death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy, from any cause related to or aggravated by the pregnancy or its management but not from accidental or incidental causes.”¹

Maternal deaths have been divided into two types, direct and indirect causes. Direct causes include maternal deaths due to pregnancy-related complications during pregnancy, childbirth, and puerperium. These include hemorrhage, sepsis, and hypertensive disorders of pregnancy. Indirect deaths are due to pre-existing maternal medical conditions, which may get aggravated by the physiological effects of pregnancy, and are not due to direct obstetric causes.² Indirect causes are responsible for 27% of maternal deaths.³ Indirect causes have been found to be more prevalent in Asian and sub-Saharan African countries,⁴ and it is important to explore the causes of indirect maternal deaths in these locations. Although deaths due to human immune deficiency virus may be more prevalent in African countries, it may not be true for Asian countries.⁵ Similarly, suicide is an important cause of maternal deaths in some Nordic countries.⁶ However, infections such as hepatitis E and tuberculosis are more prevalent in Asian and African countries.^7,8 Anemia during pregnancy contributes to both direct and indirect causes of maternal deaths. In a cohort of 100,000 women from Nigeria, anemia was responsible for 61% cases of near misses and 32% of maternal deaths.⁵ Similarly, types of cardiac diseases such as cardiomyopathy are more common in developed parts of the world,⁹ although cardiac disease is the most common cause of indirect deaths in the United States.¹⁰

Recent literature has shown an increase in the indirect causes of maternal deaths. This may be due to better and more effective management of those conditions that contribute to direct maternal deaths. In a population-based survey from Turkey of more than 800 maternal deaths, the proportion of indirect deaths increased from 45% in 2012 to 55% in 2015.¹¹ In a questionnaire-based survey from Iran, indirect maternal deaths accounted for 52% over a period of 10 years.¹² The main cause for indirect maternal death was cardiac diseases, followed by malignant diseases. Heart disease has also been found as a major cause of indirect maternal deaths among South African women, where rheumatic heart disease followed by cardiomyopathies was identified as important causes of maternal deaths.¹³

This retrospective audit was conducted at a tertiary care hospital in Pakistan, to identify the major causes of indirect maternal deaths. Literature review from our country has reported direct causes of death; hence, the aim of the study was to identify maternal deaths due to indirect causes.

Methods

This study was carried out at the Department of Obstetrics & Gynecology Unit II, Ruth Pfau KM Civil Hospital and Dow Medical College, Karachi, Pakistan, a tertiary care referral hospital. The delivery suite is divided among three units, for administrative purposes. Each unit carries out emergency duty twice a week. The hospital is equipped with an intensive care unit, blood bank, and a high-dependency unit (HDU). It receives referrals from Sind and Baluchistan provinces, as well as referrals from all secondary care hospitals of the city.

The study population included all women giving birth in the unit during the study period, January 2018 to December 2020. Data were collected from department's maternal morbidity and mortality meeting. The maternal deaths were recorded in a predesigned questionnaire. All maternal deaths reported during the study period were included. The forms were completed by the treating doctors, and were reviewed by the consultants to ascertain the cause of death. Once a consensus was reached among treating consultant, intensivist, and HDU doctors, then the maternal death was classified.

Maternal death was defined according to the World Health Organization (WHO) international classification of diseases. The variables recorded included age, registration status, parity, and gestational age at the time of admission, mode of delivery, and perinatal outcome. A woman was considered registered if a health care provider examined her thrice. Gestational age was calculated from the first available ultrasound or from the date of the last menstrual period. The timing of death, that is, occurring during antenatal, intrapartum, or post-partum period, was also noted. Indirect causes were classified into cardiac, hepatic, respiratory, and miscellaneous. Cardiac diseases were diagnosed on the basis of history, chest X-ray, and echocardiography. Hepatic conditions included acute hepatitis and chronic liver diseases. Maternal outcomes included mortality and mode of delivery. Perinatal outcomes included preterm birth, fetal death, and neonatal death. Fetal death was defined as intrauterine death after 27 weeks of gestation. Neonatal death was defined as death occurring within 7 days of birth.

The role of three delays in the maternal death was also evaluated. The three delay model introduced by Thaddeus in 1994 identifies delays associated with maternal mortality.¹⁴ This model has been used globally for the analysis of maternal deaths.¹⁵ Delay 1 is labeled when there is delay in seeking medical advice, delay 2 refers to delay in referral to appropriate facility, and delay 3 as delay in receiving medical attention at the facility.¹⁴ Improvement in infrastructure and basic health services has resulted in identifying the third delay as an important cause of maternal death.

Ethical approval was obtained from the institutional review board. Data were analyzed using Stata version 11. Mean, frequency, and percentages were calculated where appropriate. Mean and standard deviations were reported for continuous variables.

Results

During the study period, January 2018 to December 2020, the total number of deliveries was 12,135, with 11,791 live births.

Total maternal deaths during this period were 96 generating a maternal mortality ratio of approximately 800/100,000 in this cohort. Out of these, 70 (72%) maternal deaths were due to direct causes (Table 1), and 26 (27%) were due to indirect causes. Hemorrhage and sepsis were the major direct causes of maternal deaths with 29 deaths (41% of direct causes) each (Table 1).

Table 1.

Causes of direct maternal deaths during 2018–2020.

Cause	2018	2019	2020	Total
Hemorrhage	16	06	07	29 (70%)
Hypertension	07	03	02	12 (17%)
Sepsis	06	14	09	29 (70%)
Total	29	23	18	70 (100%)

Among the indirect maternal deaths, the majority of the women (16, 61%) were between 25 and 30 years of age. The mean age was 27 ± 4.1 (range: 20–35) years. The mean gestational age in the study was 33 ± 45 (range: 22–39) weeks. A majority of women delivered for the first or the second time. Table 2 shows the demographic characteristics of the indirect death population. Eighteen (69%) of the women were not registered, and only eight had been registered with a health care provider. Only two women were aware of their pre-existing medical illness. Cesarean section (13, 50%) was the main mode of delivery, whereas 11 (42%) were delivered via the vaginal route (Table 2). Two (7%) women remained undelivered during the study. Cardiac and hepatic diseases, together were responsible for 12 (46%) of indirect maternal deaths. The cardiac conditions included valvular heart disease, cardiomyopathy, cardiac failure, and suspected myocardial infarction (Table 3). Among women with an hepatic cause, half presented with nausea, vomiting, and jaundice, and half presented with an altered level of consciousness. Coagulation abnormalities were observed in all six of the patients. These women had an average bilirubin level of 12 mg/dL (range: 3–20 mg/dL) and blood glucose level of 50 mg/dL (42–90 mg/dL) at the time of admission in delivery suite. There were 100% perinatal deaths among the group of women with a clinical diagnosis of acute fatty liver of pregnancy (AFLP). Other common causes of indirect mortality included pulmonary diseases (5, 15%), followed by infections and anemic failure with 3 (11%) each (Table 3). One woman was diagnosed with multidrug-resistant pulmonary tuberculosis and died due to bacterial pneumonia during the postnatal period. Live birth rates for newborns was 9 (34%) in the study group. Women stayed in the intensive care unit for a median duration of 4 hours (interquartile range 4 to 30).

Table 2.

Demographic details of indirect maternal deaths (n = 26).

Age (years)
20–24	6 (23%)
25–30	16 (61%)
31–35	4 (15%)
Parity	1.84 ± 1.4
Registration status
Registered	8 (31%)
Non-registered	18 (69%)
Mode of delivery
Cesarean section	13 (50%)
Vaginal delivery	11 (42%)
Undelivered	2 (7%)
Time of maternal death
Antenatal	2 (7%)
Intrapartum	4 (15%)
Postnatal	20 (76%)
Fetal outcome
Alive	9 (34%)
Intrauterine death	14 (53%)
Neonatal	1 (3%)
Undelivered	2 (7%)

Table 3.

Causes of indirect maternal deaths (n = 26).

Cardiac	6 (23%)
Valvular	2 (7%)
Cardiomyopathy	1 (3%)
Cardiac failure	2 (7%)
Suspected MI (myocardial infarction)	1 (3%)
Hepatic	6 (23%)
Pulmonary causes	5 (15%)
Infection	3 (11%)
Anemic failure	3 (11%)
Transfusion-related acute lung injury	1 (3.8%)
Anesthesia complications	1 (3.8%)
Intracranial hemorrhage	1 (3.8%)

Substandard care identified in the form of three delays was observed and is summarised in Table 4.

Table 4.

Distribution of the three delays among women with indirect maternal deaths (n = 26).

First delay (seeking medical attention)	10 (38%)
Second delay (referral to appropriate facility)	9 (34%)
Third delay (receiving medical attention)	7 (26%)

Discussion

Pre-existing maternal health conditions are not only responsible for maternal deaths, but they are also responsible for severe maternal morbidity and contribute significantly to perinatal mortality. Globally, indirect causes have been found to be responsible for 27% of maternal deaths.³ In our study, the indirect causes were also responsible for 27% of maternal deaths. The direct causes of maternal death in the study included hypertensive disorders, hemorrhage, and sepsis. The maternal mortality rate (MMR) for Pakistan according to the latest survey by the National Institute of Population Studies is 186/100,000.¹⁶ This rate is 26% higher for rural areas. Our mortality rate is higher than that of the national MMR due to selection of patients as the institution is a tertiary referral center, and often receives critically ill patients from the province.

A retrospective audit of 10 years from India also reported 27.5% indirect maternal deaths.¹⁷ The maternal deaths due to indirect causes have also increased in the United Kingdom in the last decade. The latest confidential enquiry into maternal deaths report has shown indirect causes to be responsible for 58% of deaths.¹⁸ Cardiac diseases and neurological conditions remain the most important causes of maternal deaths in UK.

The mean age of women in our study was 26 years. Rafiq et al.¹⁹ in a retrospective audit from a neighboring province also showed 46% of maternal deaths occurring between 26 and 30 years of age. The latest survey from our country also highlighted two age groups for maternal deaths, 35–39, and women between 45 and 49 years.¹⁶ The survey found the lowest mortality rates for age group between 20 and 24 years. Although multiparity and grand multiparity are commonly associated with maternal deaths,²⁰ this was not observed in our study; the majority of the women delivered for the first or the second time. Mittal et al. in their study of 369 maternal deaths have shown 56% of maternal deaths among multiparous women.

Cardiac disease has become an important cause of maternal death. In the United States, cardiac disease is responsible for 26% of maternal deaths during pregnancy and puerperium.²⁰ In our study, the cardiac conditions of rheumatic valve disease and cardiomyopathy were observed. There were six maternal deaths attributed to cardiac conditions. One of the cardiac deaths occurred due to delay in appropriate referral. The patient was registered for her cardiac condition of rheumatic valve disease at a tertiary care cardiac center and was referred to us at the time of delivery. Two days after an uneventful vaginal delivery, she was referred back to the cardiac center, from where she was discharged, in a stable condition. She developed shortness of breath after 24 h and was readmitted, where she died within 30 min. Pulmonary edema was observed in four women, who were brought in a moribund condition, and echocardiography could not be carried out to exclude cardiac conditions as the main reason for death. Among the pulmonary causes, one woman had a history of pulmonary tuberculosis, and during pregnancy suffered from multidrug-resistant bacterial pneumonia, and died during the postpartum period.

Hepatic disease during pregnancy is an important cause of maternal death. We have previously reported on hepatitis E infection morbidity and mortality in our situation.²¹ Of all the indirect maternal deaths, there were six (23%) patients in whom hepatic causes were suspected. Hepatitis A and E infections were ruled out in one woman, but the diagnosis of AFLP could not be confirmed. With a higher rate of hepatitis E infection in the area, these women with jaundice may have had acute hepatitis, leading to death.

Anemic failure was responsible for 3 (11%) maternal deaths. The prevalence of anemia among the reproductive age group in Pakistan has been estimated to be around 50%.²² Poor nutrition, low socioeconomic condition, and repeated childbirths are common reasons for an increased prevalence of anemia. Both anemia and hepatitis are considered to be important contributors of indirect maternal deaths in low- and middle-income countries.¹⁷ One maternal death was due to an anesthesia complication of failed spinal anesthesia. There was one maternal death due to transfusion reaction following a blood transfusion at a primary care hospital.

In our study, only two women were aware of their pre-existing health condition, and were registered at appropriate centers. This indicates the importance of preconception clinics, and importance of combined medicine and obstetric clinics in low-resource settings. The lack of antenatal care prevents the awareness about pre-existing medical conditions which may be aggravated by the effects of pregnancy. We did not encounter any maternal death due to psychiatric or mental health conditions. This may be because of under reporting, lack of awareness on the part of women and their families, or referral bias. Our tertiary center receives referrals from secondary and primary care centers and from private hospitals for surgical and radiological intervention and for intensive care facilities.

A lack of awareness about the maternal health condition was responsible for first delay observed in 10 (38%) of cases. Contributing to delay 2, delay in referral to an appropriate facility, the last National Health Survey in Pakistan had identified that 7 out of 10 women face difficulty in accessing health care.¹⁶ The reasons included permission from family, money, distance to health facility, and not wanting to visit health facility alone. A combination of factors including environmental, social, lack of medical care, genetic predisposition, and maternal health behaviors, has been identified to be responsible for maternal deaths globally as well.²³ The majority of the women seen in our hospital are brought from peripheral areas, with late-stage disease related to inadequate antenatal care and identification of underlying disease. The third delay was responsible for seven maternal deaths, with two women receiving their initial treatment at some other centers. In a 10-year retrospective audit from Egypt, the third delay was found to be responsible for more than 80% of maternal deaths,¹⁵ whereas in our study first and second delays combined together were responsible for 19 (72%) of maternal deaths.

Our study from a tertiary referral center provides an insight into the reasons for indirect maternal deaths. The majority of the reports from our part of world are about direct causes of maternal deaths. As indirect maternal deaths are responsible for one-quarter of total deaths, these needs to be evaluated more thoroughly. Awareness of pre-existing maternal medical conditions and combined care with the medical team can help in decreasing maternal deaths.

Footnotes

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship and/or publication of this article.

Ethical approval

The Institutional Review Board of Dow University of Heath Sciences approved the study (IRB-1792/DUHS/2021).

Informed consent

Written informed consent was obtained from the patient(s) for their anonymized information to be published in this article.

Guarantor

NH.

Contributorship

NH conceived the idea, researched literature, and wrote the manuscript. ZFS collected the data, researched literature, and helped in manuscript writing.

ORCID iD

Nazli Hossain

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