Maternal Morbidity and Co-morbidity During and After Pregnancy in Women in Low- and Middle-Income Countries: A Systematic Literature Review

Background For every maternal death, it is estimated that 20 or 30 women have morbidity related to pregnancy or childbirth. The majority of this burden of disease is in women living in low and middle income countries. Maternal morbidity includes physical, psychological and social ill-health. There is limited data on the strength of association between these co-morbidities. In order to address all health needs that a woman may have when attending for maternity care, it is important to be able to identify all types of co-morbidities and understand how each co-morbidity influences other aspects of a woman’s health and wellbeing during and after pregnancy. Methods We systematically reviewed published literature, in English, describing measurement of two or more types of maternal morbidity, and/or associations between co-morbidities, during or after pregnancy and childbirth for women living in low- and middle-income countries. CINAHL plus, Global Health, Medline and Web of Science databases were searched from 2007-2018. Outcomes were descriptions, occurrence of maternal co-morbidities, and associations between these co-morbidities. Narrative analysis was conducted.


Background
For every maternal death, it is estimated that 20 or 30 women have morbidity related to pregnancy or childbirth. The majority of this burden of disease is in women living in low and middle income countries. Maternal morbidity includes physical, psychological and social ill-health. There is limited data on the strength of association between these co-morbidities. In order to address all health needs that a woman may have when attending for maternity care, it is important to be able to identify all types of co-morbidities and understand how each co-morbidity influences other aspects of a woman's health and wellbeing during and after pregnancy.

Methods
We systematically reviewed published literature, in English, describing measurement of two or more types of maternal morbidity, and/or associations between co-morbidities, during or after pregnancy and childbirth for women living in low-and middle-income countries. CINAHL plus, Global Health, Medline and Web of Science databases were searched from 2007-2018. Outcomes were descriptions, occurrence of maternal co-morbidities, and associations between these co-morbidities. Narrative analysis was conducted.

Results
38 papers reporting on 36 studies were included (71,229 women; 60,911 during and 10,318 after pregnancy from 17 countries). The majority of studies (26/36) were cross-sectional surveys. Selfreported physical ill-health was documented in 26 studies but there was no standardised data collection tool used. In total, physical morbidity was included in 28 studies; psychological morbidity in 32 studies and social morbidity in 27 studies; with 3 studies assessing association between all three types of morbidity and 30 studies assessing association between two types of morbidity. In four studies, clinical examination and/or basic laboratory investigations were also conducted. There is reported association between physical and psychological morbidity (four studies); and association between psychological and social morbidity (six studies). Domestic violence increases risk of physical ill-health (two studies).

Conclusions
There is a lack of standardised, comprehensive and routine measurements and tools used to assess the burden maternal morbidity and co-morbidity in women during and after pregnancy. There is emerging data to suggest strong associations between the different types of morbidity.

Background
Maternal morbidity affects millions of women during and after pregnancy and the burden of ill-health is expected to be highest in women living in low-and middle-income country (LMIC) settings. 1 For every maternal death, it has been suggested that 20 or 30 women have morbidity related to pregnancy or childbirth. 2,3 More recent studies using new and comprehensive assessment tools suggest that the magnitude of maternal morbidity is much larger than previously estimated. 4,5,6 International targets and the Sustainable Development Goals have a new focus; in addition to preventing maternal mortality, improving health and well-being, and, "survive and thrive" are the new goals. 7 There is international agreement that all women have the right to the highest attainable standard of health and well-being, including during and after pregnancy and childbirth. 7,8 Estimates of morbidity have until now largely focused on acute and/or severe compilations such as haemorrhage, sepsis, and eclampsia. 9 The current definition of health is "a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity". 10 Regarding maternal ill-health or morbidity, a suggested definition is "any health condition attributed to and/or aggravated by pregnancy and childbirth that has a negative impact on the woman's well-being". 11 This definition can include physical (such as medical, infectious, obstetric), mental (or psychological such as depression, suicidal ideation) and social co-morbidities (such as domestic violence, substance misuse); that are attributed to and/or aggravated by pregnancy. 5,11 In order to address all health needs that a woman may have when attending for maternity care, it is important to be able to identify all types of comorbidities and understand how each co-morbidity influences other aspects of a woman's health and wellbeing during and after pregnancy. To date, there is a lack of data regarding the measurement and burden of disease described as "maternal morbidity" or "maternal co-morbidity". Additionally, there is a lack of understanding of how best different components of maternal ill-health are measured; the descriptions of co-morbidities, and if and how co-morbidity are interlinked and associated.
Objective A systematic review of the literature was conducted for studies from LMIC that measured different types of maternal morbidity and/or associations between co-morbidities. We included studies which assessed two or more types of maternal morbidity in women during and/or after pregnancy. We assessed approaches and tools that were used to collect the data, including, self-reported subjective measures and/or objective measures such as clinical examination and/or use of investigations for the different types of maternal morbidities as reported by authors. We describe how and what different types of maternal morbidity (physical, psychological, social) were measured and if there were any reported associations between these.

Data sources and search strategy
This protocol is registered in PROSPERO (CRD42018079526). Relevant articles published between January 2007 and December 2018 were identified using a structured search strategy in four electronic databases: CINAHL Plus, Global Health, Medline and Web of Science. A search strategy was developed using thesaurus (including MeSH) and free-text terms for "maternal morbidity" and associated keywords, were used as main search terms. For each aspect of maternal morbidity ("physical", "psychological", and "social") search terms and related keywords were selected (Supplementary Table 1). Reference lists and bibliographies of key topic articles were also searched and any additional papers that met the inclusion criteria were obtained.

Inclusion and exclusion criteria
The study population was limited to women during pregnancy, childbirth or up to twelve weeks postnatal. Studies were excluded if; (i) they reported one type of maternal morbidity only, (ii) examined trend, risk factors or associations only with no estimates of prevalence of the type of morbidity reported, or (iii) reported severe or life-threatening complications of pregnancy, that would require emergency obstetric care. The review was limited to studies from LMIC as defined by the World Bank. Language was limited to English.

Selection and data extraction
One researcher screened all titles and abstracts. A sub-sample (20%) were double screened by the second researcher. Evaluation of full-text papers was done independently by two researchers with reasons for exclusion recorded and any discrepancies were discussed with a third researcher.
Information was extracted into a pre-designed summary table and included data on location of study, study dates, study design, study population, types of maternal morbidity reported, methods of measurement, timing (pregnancy phase) of the assessment and whether or not associations were reported (Supplementary Table 2). Throughout the reviewing and extraction processes, articles where uncertainty existed were discussed by all researchers to reach consensus.

Quality assessment
Appraisal of the quality of included studies was conducted based on descriptions of maternal morbidities, sampling methods and completeness of data reporting. The quality of evidence for each study was assessed using the Grading of Recommendations, Assessment Development and Evaluation (GRADE) tool adapted from the Critical Analysis Skills Programme (CASP) tool. 12

Data synthesis
A narrative synthesis approach was used to describe outcomes including: types of maternal morbidity measured which were categorised as physical (such as medical, infectious, obstetric), psychological (such as depression, suicidal ideation) , and social (such as domestic violence, substance misuse); approaches used to collect data (self-reported or determined by a healthcare provider); data collection tools used (standardised validated tool, or study specific); measurements of maternal comorbidities; and reported associations (if any) between different types of maternal co-morbidities.

Results
By combining the search terms, 2840 studies were identified from the four databases and after screening for relevance, 58 were retrieved for full text review (Figure 1). Upon applying the eligibility criteria, 38 articles met the inclusion criteria. Two studies were conducted by the same authors group. [13][14][15][16] In these publications, the same methodology was reported in two papers, but there was a different emphasis on the results and outcomes reported per publication. For the purposes of this review, the first publication is referenced in the methodology section. Both publications were included in the summary tables and the measurement and/or associations for each publication are described in the results section. The majority of studies (92%; 33/36) were considered to be of medium quality.

Geographical spread
The 36 studies were from 17 different countries, with the majority (15 studies) from Sub-Saharan Africa. Eleven were conducted in low-income countries and six in middle-income countries (four lowermiddle and two upper-middle income countries).

Study design, source of data and data collection method
Twenty-six studies used a cross-sectional survey study design. Four studies were observational prospective cohort studies . 13,17,18,19 One study was a case control study. 20 All 25 studies used faceto-face interviews or consultations to collect self-reported primary data from women using questionnaires. Most of the studies that collected primary data, relied on women's self-reported symptoms (n=28). In four studies, clinical examination and/or laboratory tests were also conducted. 6,18,21,22 Three studies extracted data using secondary data analysis of large databases of hospital admissions, discharges or birth registers. 23,24,25 In these secondary data analyses authors used their own data collection tool, with little details of the variables extracted. One study extracted data from medical case notes retrospectively (Supplementary Table 2). 26

Physical morbidity
Twenty-eight studies reported on different types of physical morbidity; three of which assessed a preselected population including women with HIV 34,41 or women with gestational diabetes. 37 A variety of data collection tools were designed and used but these were generally not well described. The most commonly reported physical morbidities were anaemia in six studies (prevalence range 5.0-57.7%), 6,18,20,21,30,48 and HIV in nine studies (prevalence range 3.0 -16.0%). 6,15,27,31,34,35,42,47,49 There was a variety of other types of physical morbidities, with wide ranges of measurements for some conditions such as antepartum haemorrhage; nausea and vomiting; preterm labour; fever; malaria; reproductive or sexually transmitted infection; urinary tract infection (Supplementary Table 3). Some authors used summative aggregated measures, for example "gynaecological and obstetric problems" as occurring in 10-22% of women; "multiple morbidities" in 60% of women or "at least one reported symptom" (44% occurrence). 20,45,48 One study used antenatal hospitalisation as a "proxy" for physical morbidity (55.4% of women) 44 Table 3).

Domestic violence
Fourteen studies assessed domestic violence, 15,16,21,23,26,29,34,37,38,42,44,46,47,49 and a variety of data collection tools were used. Most authors used their own definitions and questionnaires to screen for domestic violence. Four studies used all or part of internationally recognised questionnaires ( Table   1). 15,16,38,44,46 Different types of domestic violence assessed included: disrespect, forced sex, intimate partner violence , physical assault , severe psychological abuse and verbal abuse . Some authors used descriptions of domestic violence were aggregates or summative measures, for example, terms such as "multiple acts of physical violence" and "physical and/or sexual abuse". 37

Associations between different types of morbidity
For physical morbidity, there was an association between increased psychological morbidity in women with obstetric complications (haemorrhage, infections, incontinence, prolonged labour, Caesarean delivery, low birth weight baby, stillbirth, neonatal death) ( Table 2). 6,24,40,44,49 In pre-selected populations, women with gestational diabetes were not more likely to have psychological morbidity (depression) 37 , but women with HIV were more likely to have social morbidity (domestic violence). 16 Psychological morbidity was more common in younger women 41 and amongst women with social morbidities such as domestic violence or trauma 25,36,46 unwanted pregnancy 17,40,49, and poor social support ( Table 2). 40 For social morbidity, there was an association between women with substance misuse (alcohol) and domestic violence 47; and domestic violence was also associated with neonatal death 47 and maternal complications ( Table 2). 45 Due to the heterogeneity of the studies, metaanalysis of the strength of associations were not possible.

Main findings
There is emerging evidence of a high burden of morbidity and co-morbidity in women during and after pregnancy, living in LMIC, as well as emerging evidence of associations between physical, psychological and social morbidity, suggesting that maternal morbidities are inter-linked. However, there is still limited data on the strength and direction of the associations between the different types of morbidity.
There was an apparent lack of standardisation of definitions and data collection tools used to measure different types of maternal morbidity. The EPDS was the most common validated data collection tool used to assess psychological morbidity in the included studies, but with different cut-off scores used to determine the risk of "depression" (ranging from [4][5][6][7][8][9][10][11][12][13]. Similarly, a variety of different validated data collection tools were used to assess domestic violence and/or substance misuse as components of social morbidity. Physical, psychological and social morbidities were often described as aggregates or summative measures, limiting comparability of findings.

Strengths and Limitations
To the best of our knowledge, this is the first systematic review to assess maternal co-morbidities and the type and level of association between these. Many studies relied on recall of experience of morbidity and much of the primary data collected was symptom-based rather than "diagnosed". In this review, only four studies triangulated self-reported symptoms with findings from clinical examination and/or basic laboratory investigations. Assessments of measurements of ill-health based on self-reporting may be valid with regard to the experienced ill-health by women but do not provide accurate burden of disease estimates. No study described or used an internationally recognised disease classification to assess physical morbidity. Internationally recognised data collection tools were used to assess psychological and social morbidity, but these often used different cut-off scores.

Interpretation
Valid comparable measurements of maternal morbidity and co-morbidity to date are limited, and this confirms the need for a new approach and focus. 68,69,70 It will be important for future healthcare practice and research to agree and apply: (a) common identification criteria for different types of physical, psychological, and social morbidity; (b) standardised and validated data collection tools that can be used in different languages and at all levels of healthcare; with, (c) validation of self-reported measurements of maternal morbidity (experienced by women themselves) compared to clinical assessment, investigations and diagnosis determined by a healthcare provider. 6,68,69,70 More recognition must be given that maternal morbidity is often not a single disease condition in isolation but more complex with important associations between different morbidities. This has implications for screening and management of ill-health during and after pregnancy.

Conclusions
To date a range of methods and tools have been used to assess maternal morbidity and co-morbidity.
The maternal morbidity estimates generated using these methodologies and tools, while useful as a guide, cannot be considered truly representative of the burden and range of maternal morbidity conditions that have a negative impact on a woman's wellbeing during and after pregnancy. The suggested World Health Organization (WHO) definition of maternal morbidity in principle, provides such a framework, but challenges remain to map out comprehensive, feasible and acceptable assessment stages, approaches and tools. 11 Comprehensive and routine measurements of maternal morbidity and co-morbidity are necessary to inform policy and program decisions and for resource allocation for antenatal and postnatal care. 5 Improved measurement of maternal morbidity and comorbidity will also allow for comparison of the burden of disease across settings within and between countries. There is need for a sustainable way to provide good baseline maternity care for all, and This systematic review did not involve contact with any human participants, and therefore no ethical approval was needed. This study was conducted in compliance with the established ethical guidelines of the Declaration of Helsinki.

Consent to publish
Not applicable.

Availability of data and materials
All the sources of data are publicly available and referenced in the document.

Competing interests
The authors have no competing interests to declare.

Authors' contributions
MMc and NvdB were responsible for the study inception and design. MMc and SZ performed the data extraction. MMc and NvdB interpreted the data and wrote the manuscript. All authors have read, critiqued and approved the final manuscript.