Maternal, Foetal and Service-Related Risk Factors for Stillbirths During Conict Situation, Yemen, 2015-2016

Background: Stillbirth is a silent traumatic canker which is a major concern of various individuals, health institutions and the country as a whole. Stillbirth remains a Global major problem responsible for nearly three million deaths. Study objectives: To estimate the stillbirth rate (SBR) in Sana’a, Yemen and to identify potential risk factors for stillbirth. Methods: A community-based prospective cohort study was carried out between 8/2015 and 12/2016. Nine-hundred and eighty pregnant women were identied for the outcome of their pregnancy. We employed binomial regression together with generalised linear models. Results: The study included 952 pregnant women with 44 stillbirths. The stillbirth rate was 46.2 per 1000 and 45.2 per 1000. In multivariable analysis teenage mothers’ age at rst childbirth (< 20 years) (RR 3.70), women with anemia (RR=2.23), smoking snuff (RR = 4.27), prolonged labour (> 24 hours) (RR = 2.02), prolonged rupture of membranes ( ≥ 24 hours) (RR = 2.22), foetal malposition (RR = 4.60), low birth weight (RR = 14.90) and foetal gestational age (weeks) (RR = 5.60) were signicant factors associated with increased risk of stillbirths. Conclusions: This study identi ﬁ ed many risk factors of stillbirth that are amenable to intervention. Encouraging women to deliver at health facilities, providing better management of obstetrical complications, proper antenatal care, and prompt referral services are essential for reduction of stillbirths in Yemen.


Introduction
Stillbirths represent a devastating pregnancy outcome and has a high burden for women, families, communities, and health system. The estimated average global stillbirth (SB) rate in 2015 was 18·4 per 1000 births with an estimated 2.6 million babies were stillborn at 28 weeks or more in 2015 [1]. Everyday more than 7,300 babies are stillborn which place stillbirth as fth on the list of causes of death worldwide [2].
About 98% of stillbirths occur in low and middle-income countries (LMIC), where the birth registration coverage was low [1]. The SB rate in the LMIC (which includes Yemen) was 32/1000 births compared to < 5/1000 births in the High Income Countries (HIC) [3]. Stillbirth is closely related to maternal and neonatal mortality and with the care received during pregnancy and delivery [4].Previous study shows an increase of 17% in stillbirth during the prior four years in Yemen [5]. Recent report by the United Nations Population Fund (NFPA) revealed that about 14.8 million people lack access to basic health services [6].
Four years into con ict, an estimated two million pregnant and lactating women will be at risk of death if famine strikes. Some 1.1 million are already acutely malnourished, heightening the chance of miscarriage and stillbirth [7].
Yemen's health indicators are among the lowest in the region and reproductive health situation is one of the least favourable in the Arab world. One hundred forty eight women per 100,000 live births die as a result of complications of pregnancy and childbirth, making maternal death the leading cause of death among women of reproductive age in Yemen [8]. with a lifetime risk of death of 1 in 60 compared with a ratio of 12 and lifetime risk of 1 in 4900 in the developed countries [9] and under-ve mortality rate was 42 deaths per 1000 live births compared with a rate of 6 in the developed countries [10]. Neonatal mortality currently represents nearly half of the infant mortality with 26 neonatal deaths per 1000 live births and among all under-ve deaths in 2013 in Yemen, 48 percent occurred during the neonatal period [8].
Yemen rank 158 out of 193 countries and one of the rst Arabic countries with a highest stillbirth rate. of 23/1000 live birth [11]. Furthermore, only 45% of all deliveries are attended by skilled personnel [8].
In Yemen, 30% of births take place at a health facility with just 45% of deliveries attended by skilled birth attendants. In order to plan effective interventions, it is crucial to estimate the rate and determine the risk factors linked with stillbirth via a community-based prospective study. Previous estimation of SBR in Yemen were either from retrospective hospital-based study by non-governmental organization (NGO) household surveys; which have limitation with selection and recall bias. In addition, risk factors for stillbirths in Yemen were poorly recorded and not well understood. Therefore, the aim of this prospective follow up community-based study was to estimate the stillbirth rate and identify the potential risk of stillbirth in Yemen's communities.

Study design and study population
This is a prospective community-based cohort study, which was conducted in Sana'a City, the capital of Yemen from 1 August 2015 to 31 December 2016. It was conducted among pregnant women of age 15 years to 49, residing in the ve districts of the Sana'a City Governorate, Yemen. Sana'a City [12]. All pregnant women were followed up to seven days post-delivery or 7 days following termination of their pregnancies (spontaneous or induced abortion). Sana'a City governorate has an estimated population of 2.35 million, with approximately 521,862 being in the reproductive age group, according to an annual statistic health 2014 reported by ministry of public health and population (MoPHP) of Yemen [13]. In Sana'a city there are 234,020 households with 1,619 Enumeration Areas (EAs) [12]. Five districts were chosen by simple random sampling account for 863 EAs which cover 53% of the selected households of total. Within the 5 districts the sample was selected in two stages. In the rst stage, 49 EAs were selected from the 863 EAs within the 5 districts using probability proportional to size (PPS) method (Fig. 2). In second stage, twenty households were picked from each EA (cluster) by systematic probability sampling (SPS) [14] from a list of houses provided by the Sana'a city authority [15]. Finally, one respondent tting eligible criteria was selected from each household. Only women with singleton fetuses were included in the study.
Ethical approval was obtained from the institutional review board in the Ministry of Public Health and Population, Yemen. A consent form was signed by all participants before conducting interviews.

Data collection
Data were collected by a trained midwife. Total of thirteen midwives were trained in local cultures, languages, privacy belief con dentiality and instructed in how to build relationships. In addition, they were trained in how to use the questionnaires and conduct interview. The questionnaire sought information concerning socio-demographic characteristics (age, residence, education, parity, etc.), along with past awareness of stillbirths, both prenatal and antenatal care, traditional practices, current birth methods, breastfeeding and condition of newborns soon after birth. Information's were gathered through face-to-face interview using a semi-structured form. Baseline information were collected at recruitment stage and follow up information were collected at monthly interval up to seven days post-delivery or 7 days following termination of their pregnancies (spontaneous or induced abortion). Information at baseline and after delivery were collected by face to face interview. All women were contacted by telephone during monthly follow up by the interviewers with the supervision of the principal investigators.
Women were contacted within three to four days of the scheduled day and at least 5 attempts, at different times of the day and early evening, before they were considered to be lost-to follow-up from the study. The completed questionnaires were checked on daily basis by the investigator before left the study eld and any inconsistencies and inaccuracies were corrected.
This study aimed to estimate stillbirth rate and look into the factors linked to stillbirth during con ict situation. Stillbirth was de ned as: pregnancy loss taking place following 7 completed months of gestation (stillbirth); and calculated the stillbirth rate as (this is the number of babies born with no indication of life after 28 weeks or 7 months' gestation per 1000 pregnancies).

Data management and analysis
Raw data were entered into SPSS Software (SPSS Inc., Chicago.II. USA, version 23.0) for data management. The data were checked prior to being analysed and cleaned; described using frequencies and percentages tables along with identifying outliers. Only subjects with complete information on variables included in the nal analysis. The quantitative variables were handled in the analysis by grouped (e.g. age was grouped into less than 18 years, between 18 and 34 years and 35 years and more).
Cleaned data were then transferred into Stata 12 (Stata-Corp, Texas 77845 USA) in order to estimate adjusted Relative Risk (RR) and 95% con dence intervals (CIs) of the independent variables on stillbirth.
Adjusted RR was estimate using multivariable generalised linear models (GLMs) regression analysis with a log link and binomial distribution.
All variables were initially included in the analyses. However, only variables associated with stillbirth giving a P-value < 0.25 were retained in the model, and as well as the step-wise backward elimination method was performed to build the nal multi-variable model [16]. Two-sided test with level of signi cant at alpha = 0.05 was used.

Results
Outcome pregnancy: A total of 980 pregnant women were identi ed in the 49 clusters. Nine hundred and fty-two (952) pregnant women were included in the nal analysis ( Figure 1). This study included a total of 44 stillbirth (SBR = 46.2 per 1000 births, 95% CI: 32.7-59.3) and the remaining nine hundred eight (908) mothers with live single birth completed the 7 days follow-up (Table 1).  (Table 3). Twelve clusters seem to have the highest stillbirth's rate and represent 66 % of the total stillbirths. Seven clusters are slum areas and form around one third (32%) of the total stillbirths. There was no remarkable differences in proportion of stillbirths between urban (4.7%) and slum areas (4.6%). Socio-demographic factors (Table 4A) There is a highly significant association between stillbirth and mother age at birth. With regards to age at birth, teenage mothers (aged < 18) and older women (aged 35    Excludes primipara (222 cases), 2 One mother was not Hb tested.
Special habits factors (Table 4C) The unadjusted analysis showed that mothers who used orange snuff (smokeless tobacco) had a signi cantly increased risk of stillbirth (RR 4.28; 95% CI:      In the multivariate analysis, the risk of perinatal death was adjusted for socio-demographics factors, prenatal and past obstetric factors, special habits factors, birth factors and foetal factors. Backward elimination of the variables one by one was done to obtain the nal model (Table 6). In this model, the variables that are observed to signi cantly in uence perinatal deaths are mother's age at birth, maternal anaemia, prolonged labour, baby's position, newborn birth weight and foetal gestational age.  [5] and the data collected from a sub-national household survey conducted in six rural districts of four Yemeni provinces in 2008-2009 [17]. It is also higher than SBR in other EMR countries such as Kuwait [18], Palestine [19] and Pakistan [20]. Our study was a community-based study within households in Yemen, and the burden of stillbirths can be expected to be much higher at home than the hospital setting. In Yemen, the majority of deliveries (70%) occur at home.
However, the majority of stillbirths in the study occurred in health facilities compared to home birth (5.5% vs. 3.3%). The hypothetical explanation to this is that, pregnant women probably sought medical care only when complications arose during labour and after a protracted period [21]. Hence, coupled with the unavailability of specialized perinatal care units in many hospitals in Yemen, by the time these women arrived at the hospital much damage could have been done and rarely would the child be safe from stillbirths. In addition, the possibility that mothers might be harmed at facilities, due for example to poor infection control or other human errors, cannot be ruled out [22]. This may explain why the level of stillbirth in this study is different between home and hospital deliveries. In addition, Essential public services, including healthcare crucial to support mothers and childbirth, are on the brink of total collapse.
Only 51 per cent of all health facilities are fully functional due to ongoing war and even these face severe shortages in medicines, equipment, and staff. Since the mothers and babies are amongst the most highly vulnerable in Yemen. Every two hours, one mother and six newborns die because of complications during pregnancy or birth [23].
Previous study conducted in Yemen reported that women who suffered complication during home birth and were taken to the hospital were at a high risk of death, and that 44% of home births developed delivery complications [5]. In addition, there is inadequate number and poor quality of health facilities and services due to the limited nancial resources needed for improving the health sector. This is exacerbated by the high population growth rate of 4.4%, and very low health awareness at the community level, especially with respect to maternal and infant health care [8]. These structural challenges, as well as the war, security problems and the food crisis in Yemen may raise concern on the effectiveness and deliverability of antenatal and childbirth services in Sana'a city, hence, play a role in the high rate of stillbirth. This emphasises the need to minimize delays in referral and transportation of mothers in labour as well as putting appropriate measures in place to ensure e cient intrapartum management of high-risk cases.
In multivariable analysis the risk factor for stillbirths were young maternal age, anaemia, smoking orange snuff, prolonged labour, prolonged rupture of membranes, mal-position of baby at delivery, newborn birth weight and foetal gestational age.
In present study, babies born to women younger than 20 years had a signi cantly increased risk of stillbirth (aRR 3.70, 95% CI: 1.76-7.76) compared to those 20-34 years old. Similar ndings have been reported in a study from Nigeria that examined pattern and correlates of stillbirth in a hospital setting where young maternal age (< 20 years) was reported to increase the risk of stillbirth (OR 2.50; 95% CI 1.22-5.14) but this was not corrected for other risk factors [24]. There was also a higher proportion of stillbirths reported among teenage mothers when compared with older mothers (5.1% versus 0.9%, respectively) in a hospital setting in India [25]. Also, in a national survey involving 8481 deliveries in in the univariate analysis compared to the women with normal haemoglobin. This association remained signi cant in the multivariable analysis (aRR 2.23; 95%CI: 1.67-2.98). Our nding of higher stillbirth rate among anemic women support the ndings of previous studies that reported that anemic mothers and those with poor antenatal care had 8 times higher risk to have stillbirth compared to non-anemic mother and those with adequate antenatal care [27][28][29][30].
Such a great proportion of anaemia may be explained as follows: teenage pregnant women rarely receive an education so there is a high possibility they come from a poor and under-privileged family. Therefore, it is unlikely they will realise just how crucial it is to have regular antenatal care, blood tests for anaemia.
In addition, taking iron and folic acid supplements during pregnancy prevents and treats anaemia.
The use of non-cigarette forms of tobacco is prevalent or gaining in popularity in many parts of the world, including many low-and middle-income countries (LMICs) [31,32]. Non-cigarette tobacco products are often less expensive than manufactured cigarettes, and may be viewed by some as a safer alternative to smoking [33].
In Yemen commonly used smokeless tobacco are: Orange snuff (or shamma) made of powdered tobacco, lime, ash, black pepper, oils and avourings. In Yemen smoking prevalence is 11 percent of household members age 15 and older where 16% of men and 5.3% of women use smokeless tobacco in chewing form [8]. In this study, the stillbirth rate was signi cantly higher among smokeless tobacco (orange snuff) mothers than among non-users' mothers (188/1000 vs. 44/1000) with relative risk identi ed in multivariable analysis of 4.27 (95% CI: 1. 17-15.55). This is consistent with other studies that found snuff has been linked to immune dysfunction, reproductive impacts such as stillbirth and preterm birth, and cardiovascular effects, among other adverse health outcomes [34]. The cohort study of pregnant women by Gupta PC., in India found that the cumulative incidence rate of stillbirth was signi cantly higher among smokeless tobacco users than among non-users [35].
Use of non-cigarette tobacco products is a cultural norm in some areas. This has made its use to be socially acceptable in those areas. Non-cigarette tobacco may constitute some element of nicotine, and its subsequent use may result in nicotine addiction. This raises concern, particularly for non-tobacco products with high nicotine content [36]. There is also evidence suggesting that the use of smokeless tobacco products during pregnancy may increase the risk of adverse pregnancy outcomes [31].
Women who had prolonged labour (≥ 24 hours) and mal-position appeared to increase risk of stillbirths where the total cases admitted to the hospital for birth were 3622 women of them, the obstructed labour was reported in 330 cases (9.1%) making the incidence approximately 1 in 11 deliveries. The most common cause of obstructed labour was cephalopelvic disproportion (46%) followed by mal-presentation and mal-position (38.8%), thereby 164 (49.7%) were stillbirth [37], and elsewhere [3,38,39].
Prolonged rupture of membrane (PROM) de ned as rupture of membrane before onset of labour occurs in 10% of the pregnancies and increases the risk of stillbirths due to sepsis [40][41][42][43]. The latency time between rupture of membrane and birth was a signi cant risk factor for stillbirth in this study (aRR 2.22; 95% CI: 1.66-2.98). In many developing countries, the infectious disease burden during pregnancy is extremely high, and it appears that in many countries the stillbirth rate is high as a result of these infections [44]. It is also likely that reduction in amniotic uid infections due to prolonged rupture of membranes, if achievable, will also have a substantial impact on stillbirth rates. Perinatal outcomes due to preterm premature rupture of membranes (PPROM) include prematurity, neonatal sepsis, respiratory distress syndrome (RDS), intraventricular haemorrhage (IVH), risk of foetal and neonatal death [45].
Our results in the multivariable analysis indicated that the low birth weight was a leading risk factor for stillbirth and low birth weight babies were 15 times more likely to die in the perinatal period than babies weighing 2500 grams or more (95% CI: 4.30-51.75). Similarly, other studies identi ed that the low birth weight as risk of stillbirth [39,46].
Another important variable in uencing stillbirth was foetal gestational age, with the SBR reaching almost 180.2 per 1000 births among preterm babies and premature birth at the gestation age of less than 37 weeks were 6 times more likely to be associated with stillbirth compared to those who delivered at 37 weeks of gestation or more (95% CI: 2.52-12.41). Likewise, these ndings has been previously reported by other authors [47].

Strengths And Limitations
Some of the deaths that occurred at home involved did not received death certi cate and not recorded in any formal system. Therefore, many of these deaths would have been missed by facility-based studies.
The stillbirths of mothers dying during or shortly after birth would also have been missed. These retrospective surveys are the main sources of data concerning stillbirth in low and middle-income countries. All these factors were able to be taken into account in this prospective community-based cohort study and provide a thorough description of likely risk factors for stillbirth.

Conclusion
In terms of public health, stillbirth is a major problem both Yemen and other low middle-income countries.
Our ndings lend weight to arguments for sets the minimum age for marriage at 18 in accordance with the de nition of a child in the convention on the Rights of the Child.
In addition, improving maternal nutrition and provision of universal care during pregnancy and birth by trained personnel to all pregnant women are areas where priority actions should be given, and directed particularly at the most vulnerable such as the poor, the slum-dwellers and the marginalized.
Urgent action is necessary to be done by the local authority and NGOs to control smoking snuff and khat cultivation and chewing by creating awareness and increasing knowledge on the harmful effects of smoking snuff and khat chewing especially among women and the younger generations. Further, urgent need is imperative there be sustainable interventions in order to improve the country's maternal and newborn health. Urgent request is calling on all parties to the con ict and the international community to focus resources on the poor, marginalized and internally displaced communities and to protect the health care system in the country, with speci c attention to maternal and neoborn health as well as primary healthcare. Declarations Acknowledgment I would like to thank those who participated in the study. All the data collectors are recognised and thanked for their tremendous contribution during data collection.

Abbreviations
Authors' contributions AHA was the primary author, initiated the study and carried out the analysis of results and wrote the rst draft of the paper. RHZ, AAA, AB all contributed towards the design, agreed the survey structure, participated in the analysis of the data and contributed to the nal writing of the script. The authors read and approved the nal manuscript.

Funding
No funding was obtained for this study.
Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Ethics approval and consent to participate Ethics approval was granted on 15/06/2015 from the Ethical Review Board of Ministry of Public Health and Population of Yemen (G 7/77). Approval also was obtained from the local district administrative and Sana'a City health o ces. The mothers or guardians of those participating in the study gave their verbal consent. Consent to participate was incorporated in the survey itself.
Declaration I, declare that the manuscript is my original work and was conducted as part of large study that explore the perinatal mortality among pregnant women in Yemen.

Consent for Publication
Not applicable

Conflict of interest
No conflict of interest was declared.