Ethical considerations

All procedures performed in this study involving human participants were approved by Institution Review Board at the College of Medicine and Health Sciences, University of Rwanda (ethical approval No 439/CMHS IRB/2019) prior to enrolment of participants. Permissions to conduct the study was also obtained from all the health facilities included in this study. Informed written consent was obtained from all participants.

Study design

The present study used an observational case control study [44, 45] which is part of a larger exploratory sequential mixed-methods study aiming “to explore the factors associated with PPH prevention” and to develop a “risk assessment tool for the prediction and prevention of PPH” among clients of the Northern Province of Rwanda. This case control study was preceded by a scoping review [4], a qualitative descriptive study [43] and the development of a content validated risk assessment tool for the prediction and prevention of PPH (RATP) [46]. The RATP was used to explore PPH risk factors in the present case control study.

Population and setting

The target population was women aged 18 years or above, admitted to the postpartum ward after a live birth at ≥32 weeks’ gestation at the health facilities of the Northern Province of Rwanda during the period January 1^st 2020 to June 30^th 2020. The selection criteria of health facilities included their level of performance in maternal and newborn health (5362 women gave birth in selected health facilities during the study period), their location (rural versus urban), and the geographical accessibility of the health facilities to clients. Considering that the northern province is characterised by a hilly terrain, some inhabitants have difficulties to reach the health facilities as indicated by participants in a recent study [43]. The study sites were selected by the principal investigator and validated by the research committee. The Northern Province of Rwanda was purposively chosen for being in a rural area where some health centres are hard to access, and for its low uptake of antenatal and postnatal services among childbearing women [47]. We sent invitations to participate to six health facilities: 5 hospitals and one medicalised health centre. Four district hospitals and one medicalised health centre provided permission to conduct the study. Therefore, five health facilities were included in this study while one district hospital was excluded. The permission to conduct the study in the excluded district hospital was not granted in spite of the follow up made on the request. In addition, the same hospital become later a temporally Covid-19 treatment center during the period of data collection. A medicalised health centre is a new level in the health system of Rwanda deployed with capable staff (medical doctor, nurses and midwives, paramedics, anaesthesia, etc…). It is the level in between district hospital and health centre, which is equipped to attend to patients with acute life threatening conditions especially obstetric conditions [48].

Participants and data collection procedures

From the target population, the source population for the present case control study was selected to identify the outcome of interest as suggested by Song and Chung [45]. Hence, women in the postpartum period were our source population. A PPH case in our study is defined as blood loss of 500 ml or above within the first hour which is visually estimated by health care providers observing women who change the blood-soaked vaginal pads 2 times or more within the first hour after birth [6, 49, 50]. Primary PPH is also counted in case woman requires a blood transfusion for excessive bleeding after birth due to clinical symptoms and signs of anaemia or hemodynamic decompensation after birth [10] or with Hb level less than 11 gr/dL especially if symptomatic according the findings from Rwanda Demographic Health Survey 2019–20 [2]. The number of blood transfusions units administered to the client with PPH was described. Women who received a blood transfusion because of postpartum anaemia, without evidence of excessive blood loss after birth were excluded from this study. Women with secondary PPH which is characterised by vaginal blood loss (or lochia discharges) at least 24 hours after birth or six weeks after delivery [51], were also excluded from this study. The attending health care provider estimated the blood loss visually in all five health facilities. Controls were a random sample of all deliveries without primary PPH from the same source population and period of time as the cases of primary PPH. Based on the list in the birth registry, after identifying the case of PPH, the three following women who gave birth without primary PPH were selected as control cases. Hence inclusion criteria were being aged of 18 years and above, being admitted for postpartum monitoring at the health facility within the first 24 hours after birth.

After selecting eligible women for inclusion in the present study, we extracted the study participants [45], that included all cases confirmed to have primary PPH (n = 108) and a random sample of controls without primary PPH (n = 322) (Fig 1) to make a total sample size of 430 participants. Due to a limited study period, the number of study participants was slightly lower than the target sample size. A G*Power software for power analysis [52] indicated that we needed 118 cases and 354 controls considering three controls per case, with type I error of 5%, power of 80%, frequency of risk factors in control subjects of 0.2%, and cases with potential risk factors to PPH being almost twice as likely to be exposed to PPH compared to controls (odds ratio (OR) = 1.8).

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Fig 1. Selection of study subjects.

PPH: Postpartum haemorrhage.

https://doi.org/10.1371/journal.pone.0263731.g001

The research assistants (one at each of the five health facilities) were registered midwives with experience of working full time in maternity, and were recruited by the principal investigator in agreement with the health facilities’ administration. To start data collection, research assistants verbally invited women in postpartum period who met inclusion criteria to take part in the study, told them about the study. Those who agreed to participate signed to indicate informed consent. Data was collected during the hospital stay of the woman to allow the research assistant to visit the client and cross check data. Accessing clients’ charts facilitated the assessment of eligibility of study participants. Therefore, registration of client data was based on information collected from clients’ files, from maternity records completed on a regular basis on women in labour and birth, also documenting the birth outcomes, including cases that experienced blood loss during birth and immediately after birth. We also collected client data through structured interviews carried out by the research assistant with the women using the RATP to ensure the accuracy of data and to minimise missing data. After identifying a case of PPH, the research assistant was required to also identify three control participants who gave birth and who did not experience PPH within +/- 24 hours in relation to the time the PPH happened.

The RATP was translated from English to French and Kinyarwanda by a professional translator to facilitate respondents’ understanding of the tool by using their preferred language. The three languages are officially used in Rwanda. Back translation was done by an independent professional translator, to confirm that the meaning and content of the questions of the original copy had not been changed during the translation. Verification of the translated instrument was also done to ensure its validity.

As the research assistants were full-time staff working in maternity, they were able to identify cases who experienced PPH after birth during their working days. For some cases of PPH that happened during their days off, the research assistants could identify potential participants through maternity records (daily reports) and confirm whether the woman had primary PPH by asking the woman if she bled heavily and changed the blood-soaked vaginal pads two or more times during the first hour after birth. The principal investigator made regular visits to the research sites during the data collection period to ensure that data collection was being conducted as planned.

Variables under study

The dependent variable in this study was primary PPH (presence or absence of primary PPH: Case and Controls) while the presence or absence of the potential PPH risk factors among PPH and control cases were the independent variables. The RATP consists of three sections. The first, Section A consist of social and demographic characteristics of the woman: age, marital status, level of education, area of residence, accessibility to nearest health facility, use of medical insurance, use of family planning methods outside pregnancy, health facility where delivery took place, socio economic status and religion. Section B included newborn and mother anthropometry and Hb measurements: newborn weight, woman weight, woman height and woman Hb level. Section C focused on pregnancy, obstetric, intrapartum and immediate postpartum factors: primiparity, multiparity, uterine anomaly, uterine surgery (e.g. myomectomy), previous caesarean section, previous PPH, antepartum haemorrhage, HIV positive status, multiple pregnancy, anaemia, gestational diabetes mellitus, polyhydramnios, anticoagulant medications in pregnancy, severe pre-eclampsia, intra-uterine foetal death, premature rupture of membranes, prolonged labour, spontaneous vaginal delivery, instrumental vaginal delivery, in labour caesarean section, repeat caesarean delivery, labour induction, labour augmentation, administration of oxytocin for active management of the third stage of labour, episiotomy, perineal tear, vaginal wall tear, cervical tear, uterine rupture, retained tissues, uterine atony with full bladder and uterine atony with uterine inversion. Multiparity indicates the clinical case of the woman who has already given birth to more than two babies while grand multiparity is from five babies at a gestational age of 24 weeks or more as defined in literature [53, 54]. For the present study, those with gestational age of 32 weeks and above are included.

Data analysis

All 430 completed risk assessment tools (108 cases and 322 controls) were captured in an Excel spreadsheet which was exported to STATA version 15.1 to perform data analysis [55]. Data were cleaned to ensure that there were neither errors nor missing data. For data analysis, we distinguished between causes of and risk factors for PPH. Causes of PPH were classified as the ‘4Ts’ mnemonic [12]: Tone (uterine atony, uterine inversion, and full bladder after birth causing PPH), Tissue (retained placenta and retained parts of placenta, and abnormal placentation), Trauma (uterine rupture, perineal tears and episiotomy, vaginal wall tears, cervical tears), and Thrombin (coagulation disorders, consumption of anti-coagulant medications).

Among the PPH risk factors, maternal age, BMI, birth weight and maternal Hb were recorded as continuous variables for descriptive purposes and for inclusion in the final model for analysis. Maternal age was divided into 4 groups, below 25 (reference group); 25–29; 30–34; 35 and above [56]. BMI was divided into 4 groups as per WHO’s recommendation: <18.5; 18.5–24.9 (reference group); 25–29.9; ≥30 kg/m2 [57]. Infant birth weight was grouped into three categories: < 2500g; 2500-4000g (reference group); ≥4000g [58]. Hb level of the client at the time of admission to labour was dichotomized as either anaemic (Hb< 11gr/dL) or non-anaemic (Hb ≥ 11gr/dL) [2].

Data were analyzed using univariate, bivariate and multivariate techniques [59]. Univariate analysis was used first to summarize data in terms of frequency distributions of the variables under study then bivariate was used to examine the relationship between primary PPH (binary outcome variable) and each risk factor/ cause. The relationship was established between outcome variable (developing or not developing primary PPH among childbearing women in selected health facilities) and independent variables (socio-demographic variables and other potential PPH risk factors under study).

Multivariate analysis was conducted to determine to what extent the significant independent variables are in correlation with the outcome variable. The modified Poisson regression model with robust error variances [60] was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs). This model was chosen because the outcome of interest (primary PPH) was common [61, 62]. The absence of PPH was used as the reference category because we hypothesized based on previous research [4, 43] that the likelihood of PPH would be high with the presence of PPH risk factors relative to none. Statistical significance was therefore defined at 95% confidence interval and P-value of <0.05.

Extensive discussion in the literature has reached a consensus that RR is preferred over the odds ratio for most prospective investigations for its scientific meaning [61, 63]. Moreover, odds ratios are considered as more extreme than relative risks when the outcome is not rare [64, 65] (prevalence above 10% in the study population [62, 66]), and conversion of odds ratios into relative risks is known to produce biased estimates when adjusting for covariates [60, 63]. Therefore, Poisson regression, a generalized linear model with a log link and a Poisson distribution was used in this study to estimate the risk ratio because the prevalence of the outcome is not rare (prevalence of primary PPH = 25%) and the outcome variable itself is binary. When the outcome is binary, the exponentiated coefficients are risk ratios instead of incidence-rate ratios [60, 67, 68]. The results are reported in the results section.

Antepartum risk factors

Antepartum haemorrhage, multiple pregnancy, intrauterine foetal death, Hb level on admission to labour and PROM demonstrated an increased RR for developing PPH which was higher in women with these risks factors than in women without.

Antepartum haemorrhage was the strongest predictor among study participants and was associated with triple the risk for developing primary PPH. This finding concurs with the guideline released by the Royal College of Obsetricians and Gynecologists [71] in the UK, which states that PPH should be anticipated in women who have experienced antepartum haemorrhage [71]. A study in Brazil demonstrated that severe maternal outcome due to antepartum and intrapartum haemorrhage was highly prevalent [72]. Antepartum haemorrhage might be associated with placenta praevia, placental anomalies and local genital tract disorders, such as cervicitis and neoplasms. No definitive cause is diagnosed in some patients [72]. In our study, insufficient data were available to classify antepartum haemorrhage, and participants were not sure about the kind of antepartum haemorrhage they experienced. A comprehensive documentation of client obstetrical history and antepartum complications could give light to birth preparedness and early detection of PPH.

Multiple pregnancy was one of the strongest predictors of primary PPH in this study, which is similar to previous studies [10, 19, 31, 73]. The over distension induced by multiple pregnancy increases the risk of uterine atony with overstretching of uterine muscle. The WHO encourages further research to determine the role of symphysis-fundal height measurement in detecting abnormal foetal growth and other risk factors for perinatal morbidity (multiple pregnancy, polyhydramnios, macrosomia) in settings where antenatal ultrasound is not available [74]. In addition, the large placental size in multiple pregnancy increases the insertion surface area which bleeds after childbirth. Multiple pregnancy contributes to an increased fundal height which is shown to be a predictor for PPH [22]. This finding calls for more vigilance on the part of practitioners attending labour and births to identify women at risk, to have adequate preparation and plan for early intervention to prevent PPH. In this regards, as suggested by Fawcus [75], practical approaches to preventing and managing PPH in limited resource settings may be encouraged in the present study like establisment of women groups coordinated by community health worker to enhance birth preparedness and encourage peer support. “Maternity waiting areas” could be also useful in hard to reach areas whereby pregnant women are encouraged to be admitted in lodging facilities close to health facilites waiting for birth and hence allow timely management of possible complications [75].

Intrauterine foetal death (IUFD)—also called stillbirth—was prevalent in participants of our study who experienced primary PPH, again supporting the existing evidence. PPH was observed in 10% of IUFD cases in a US study [76] and in 12% of patients in a study on aetiology and maternal complications of IUFD [77]. In case of stillbirth, PPH might be associated with retained placenta which was noted in a very high number of women (23%) in a retrospective chart review to evaluate stillbirth demographics, pregnancy and maternal risk factors, and complications of labour and birth [76]. Another attributable cause for this association was disseminated intravascular coagulation as reported by evidence [77–79] which definitely lead to massive blood loss. Though global data on causes of stillbirth is limited [80], evidence demonstrates that intrapartum complications, hypertension, diabetes, infection, placental impairment, and pregnancy lasting longer than forty weeks are potential causes of stillbirth [81]; and these causes have been identified to be risk factors for PPH [22, 82]. During antepartum care, it is necessary to track patients with conditions that raise their risk of stillbirth as well as postpartum haemorrhage [83].

Our study was conducted during the Covid-19 outbreak (study period: January–June 2020). Clinicians and caregivers need to be extra vigilant for maternal complications in pregnant women with Covid-19 [76]. Creating an individual care plan for high-risk pregnancies instead of a virtual approach may improve outcomes in this type of situation [78]. Since pregnant women are potentially at risk of obstetric complications including PPH, regular consultation with a health professional is recommended throughout the course of pregnancy, because it is an optimal opportunity for healthcare providers to identify women who are at increased risk early on during pregnancy and to deliver necessary support and educate pregnant women on unexpected events [84]. Rwanda has started implementing the newest guidelines from the World Health Organization recommending the 8 contacts during antenatal period [85]. This is commendable as it is a great opportunity to reduce perinatal morbidity and mortality which includes detection of PPH risk factors and hence improve women’s experience of care.

In addition to prevalent risk factors, our bivariate analysis demonstrated significant association of other risk factors with primary PPH with a P-value < 0.05. These significant factors included maternal age (being >35 was associated with higher risk), type of health facility where birth take place, BMI, holding medical insurance, multiparity, previous PPH, anaemia during pregnancy and active management of third stage of labour. The significant antepartum risk factors for primary PPH observed in our study echoed previous evidence [19, 23]. In contrast to previous studies [10, 19, 20, 23], where these same factors were found to be predictors of PPH, our multivariate analysis did not find these variables to be associated with increased risk of primary PPH. This dissimilarity might be associated with difference in sample size and in data collection period. A large scale case control study would investigate further all potential risk factors for improved PPH prevention.

Intrapartum risk factors and causes of PPH

Low Hb level (<11 gr/dL) during intrapartum period is worth noting because it is an indication of anaemic pregnant women so that health care providers can be proactive in prevention of PPH. For participants included in this study the risk of PPH was 1.5 times higher for anaemic women than for non-anaemic women. Again, our findings are consistent with earlier research [28]. Anaemia in pregnancy is a significant public health problem around the world, particularly in LMIC’s, where it is a leading cause of maternal morbidity and mortality [86]. Anemia has long been thought to increase the risk of postpartum hemorrhage [20] and the two conditions together contribute to 40–43% of maternal deaths in Africa and Asia [87]. Severe anemia has been shown to affect myometrial contractility related to diminished transport of hemoglobin and oxygen to the uterus, resulting in tissue enzymes and cellular dysfunction [88]. According to the findings of an observational study demonstrating an association between haemoglobin level at labor and PPH [69], women with Hb of 7gr/dL or less have such a higher risk of PPH due to uterine atony than women with Hb 7.1–10gr/dL. This concur with our findings whereby 5.6% of PPH cases had received blood transfusion because their intrapartum haemoglobin was less than 7gr/dL. Any blood loss after birth that has the potential to cause hemodynamic compromise should be deemed PPH for clinical purposes; and this is likely to happen in conditions like anemia [89].

There are a few studies that link the risk of PPH to anemia levels [69]. Further researches are encouraged to explore more this area. Anemia is prevalent in our country, as it is in other LMICs, especially in hard to reach communities where access to antenatal care services might be difficult. The key findings from Rwanda Demographic Health Survey 2019–20 demonstrated that among pregnant women, those in the lowest wealth quintile are more likely to be anaemic (Hb<11 gr/dL) than other women [2]. Our multivariate analysis also demonstrated PROM to be prevalent in women who developed primary PPH which was identified as potential risk factor in earlier case control study [10]. PROM is complicated with chorioamnionitis which was found to be associated with an increased risk of severe atonic PPH in previous studies [32, 90].

For other intrapartum and immediate postpartum factors analyzed in this study, with the exception of coagulopathy, the other causes of PPH demonstrated a strong association with primary PPH (uterine atony, trauma of genital organs and retained tissues). In this study, uterine atony was found to be the most prevalent cause of primary PPH, followed by retained tissues and genital trauma. Our findings concur with previous studies highlighting that the main cause of primary PPH and the primary direct cause of maternal morbidity globally was uterine atony [6, 7, 18]. However, one other study concluded that genital tract laceration was the commonest cause of primary PPH followed by uterine atony [13]. The active management of the third stage of labour (AMSTL)with uterotonics was found to reduce the risk of PPH especially due to atonic uterus, and injectable oxytocin is the treatment recommended by WHO [37, 91].

Rwanda is applying WHO guidelines manage the third stage of labour. For all births (both vaginal and caesarean section births), it is recommended to use uterotonics to prevent postpartum haemorrhage (PPH) [91]. In spite of the widespread availability of oxytocin, some women included in our study were not given a uterotonic medication within three minutes of giving birth as an important component of AMTSL recommended by WHO [89] to prevent PPH. Our study demonstrated that 84.1% women among those who developed PPH had received an intramuscular uterotonic to manage the third stage of labour versus 90% in the control group. This rate is low compared to a prospective cohort study conducted in Uganda to understand the relative contributions of different risk factors for PPH. The results revealed that almost all (97%) women delivering at the health facilities health in rural Uganda received uterotonics. One of the factors affecting AMTSL practice identified in Tanzania, was incorrect time to administer oxytocin [92]. This is a context similar to Rwanda, where staff cannot have enough time to follow the procedure in an environment with limited staff performing multiple tasks [43]. This may be one of the reasons preventing certain women from receiving adequate uterotonic medication. This difference might be also associated with inadequate management of the third stage of labour as revealed by previous studies [4, 43, 93] in relation to factors affecting the prevention of PPH. This is also confirmed by findings from an endline evaluation of the 50,000 Happy Birthdays Project implemented in Rwanda between 2018–2020. The programme involved training midwives, nurses and other health workers to apply the Helping Mothers Survive (HMS) and Helping Babies Survive (HBS) techniques to address the leading causes of maternal and neonatal mortality including PPH. The baseline assessment demonstrated that 87.2% of women giving birth received uterotonics immediately after birth while after training, the endline evaluation revealed that 99.9% of women giving birth had received uterotonics for PPH prevention [94]. Beside medical interventions preventing PPH by usage of uterotonics, the experience of HMS simulation based training in Rwanda and in other similar settings also involve mechanical interventions such as bimanual uterine compression, the use of uterine balloon tamponade to manage and prevent PPH and its complications. These practices are commendable as they demonstrate successful knowledge and skill acquisition among frontline healthcare workers attending births, and improved clinical outcomes of childbearing women [94–96].