Rate, determinants, and causes of stillbirth in Jordan: Findings from the Jordan Stillbirth and Neonatal Surveillance (JSANDS) system

Background: Annually, 2.6 million stillbirths occur around the world, with about 98% occur in low and middle-income countries. The stillbirth rates in these countries are 10 times higher than the rates in high-income countries. Methods: An electronic stillbirths and neonatal deaths surveillance system (JSANDS) was established in five large hospitals located in three of the largest cities in Jordan in August 2019. JSANDS was developed as a secure on-line data entry system to collect, organize, analyse, and disseminate data on stillbirths, neonatal deaths, and their causes. Data on births, stillbirths and their causes, and other demographic and clinical characteristics in the period between August 2019 – January 2020 were extracted and analysed. Results: A total of 10328 births were registered during the reporting period. Of the total births, 102 were born dead (88 antepartum stillbirths and 14 intrapartum stillbirths) with a rate of 9.9 per 1000 total births. The main fetal causes of antepartum stillbirths were antepartum death of unspecified cause (33.7%), acute antepartum event (33.7%), congenital malformations and chromosomal abnormalities (13.3%), and disorders related to the length of gestation and fetal growth (10.8%). The main maternal causes of antepartum stillbirths included complications of placental cord and membranes (48.7%), maternal complications of pregnancy (23.1%), and maternal medical and surgical conditions (23.1%). Fetal causes of intrapartum stillbirths included congenital malformations deformations and chromosomal abnormalities, other specified intrapartum disorder, intrapartum death of unspecified cause (33.3% each). Maternal causes of intrapartum stillbirths included complications of placental cord and membranes. In the multivariate analysis, the odds of stillbirth for very low birth weight (<1500 gm) babies and for low birthweight babies (1500-2499 gm) were 14.1 times 4.3 times that odds for babies born with normal birth weight, respectively. The stillbirth rate was significantly higher among preterm deliveries compared to full-term deliveries (OR = 5.6).


Background
Stillbirth is considered a global public health problem particularly in developing countries. Global efforts to reduce stillbirth rate have had some impact, however, the burden still high particularly in low-and middle-income countries. The global burden of disease study reported a decline in stillbirth rates by 47.0% between 1990 and 2015 (1). Data extracted from registration systems from 157 countries reported an estimate of 2.6 million stillbirths occurred annually and showed a reduction of 25.5% in stillbirth rates for the period 2000 until 2015 (2). About 98% of these stillbirths occurred in low and middle-income countries (3).
Although stillbirths are declining in many developed countries, the stillbirth rates in developing countries are 10 times higher than the rates in high-income countries (4). Regionally, a retrospective population-based study of stillbirth in a multi-ethnic Middle-Eastern population reported a stillbirth rate of 7.81 per 1000 total births (5). The majority of stillbirths in the developing countries occur unexpectedly without a clear cause (6). It is difficult to confirm the cause because there are many factors that may contribute to the cause of a stillbirth, however, literature has categorized causes into those related to maternal or fetal conditions (7). Maducolil et al., reported that maternal factors comprised a 52.4% of total stillbirths in Middle-Eastern population and included maternal hypertension, diabetes, and other medical disorders. The main fetal factors reported in the same study were intrauterine growth restriction followed by congenital anomalies (5).
One study in Jordan has reported stillbirth rate during the period 2011-2012 and showed a stillbirth rate of 10.6 per 1000 total births (8). This study reported maternal diseases, immaturity, congenital anomalies, unexplained antepartum stillbirths, obstetric complications, placental conditions, and multiple births as the main causes of stillbirths.
The scarcity of data in Jordan on stillbirth is generally linked to the fact of that the stillbirths are not registered (9). In addition, the existing sources of data on stillbirths are liable to biases. Therefore, improving a reporting system of stillbirth and neonatal deaths is critical for tracking progress and taking appropriate actions. As a result of this limitation, an electronic stillbirths and neonatal deaths 4 surveillance system (JSANDS) was developed and established in five large hospitals in Jordan in August 2019. JSANDS was developed as a secure on-line data entry system to collect, organize, analyse, and disseminate reliable data on stillbirths, neonatal deaths, and their causes. In addition, the system registers births to use them as a denominator for mortality measures. The definition of the stillbirths and neonatal deaths used in the system were based on the international standards set by the WHO and CDC. To ensure comparability of mortality rates between different providers and to allow for international comparisons, births less than 24 + 0 weeks of gestation and terminations of pregnancy are not reported by JSANDS. This study used the data from JSANDS to determine the rate, determinants, and causes of stillbirths in Jordan.

Methods
The information on all deliveries and birth outcomes that registered in JSANDS during the period from August 2019 to January 2020 were retrieved from the system. All births and stillbirths occurred in the five large hospitals were registered with a completeness of 100%. Three hospitals were public hospitals, one was private, and one was a teaching hospitals. The extracted data included sociodemographic characteristics of both parents, delivery information (i.e. mode of delivery, multiplicity, and gestational age), new born information (status, birth weight, Apgar score) and causes of stillbirths.
In this study, stillbirth was defined as any fetal death that happened at or after 24 gestational weeks.
Stillbirths were categorized to antepartum and intrapartum stillbirths, and deaths that occur after the onset of labour but prior to birth (intrapartum deaths). The stillbirth rate was calculated as the number of stillbirths per 1000 births.

Causes of stillbirths were determined based on the International Classification of Diseases-Perinatal
Mortality (ICD-PM) that is derived from the 10th version of the International Classification of Diseases (ICD-10) developed by the WHO (10). ICD-PM is a standardized classification for reporting perinatal deaths (10). All health care professionals in the five hospitals were trained on how to assign cause of death. The doctor who is responsible for the delivery of a stillbirth has the primary responsibility to fill the form for the stillbirth, assign the cause of death, and write the ICD-10 code accordingly. ICD-10 5 codes were used to provide a common language for reporting and monitoring diseases. This allows for comparing and sharing data in a consistent and standard manner between the 5 hospitals.
Causes of deaths related to fetal condition or related to maternal condition were registered. First, the main disease or condition in fetus is determined, in which the single most important and main disease or condition of the fetus who has died is entered. This is supported by reporting any other diseases or conditions in fetus if any. Second, is the reporting of main maternal disease or condition affecting the fetus. The "most important" maternal disease or condition affecting the fetus that made the greatest contribution to the fetal death was reported. Other maternal diseases or conditions affecting fetus, if any, were also reported in this section. The stillbirth was calculated as the number of stillbirth by 1000 total births. The distribution of stillbirths according to studied characteristics were tested using Chi-square test. Multivariate analysis using binary logistic regression was used to determine factors associated with stillbirth. A p-value of less than 0.05 was considered statistically significant.

Women's demographic and maternal characteristics
During the period from August 2019 to January 2020, a total of 9983 women gave birth to 10328 babies. The women's age ranged between 15 and 48 years with a mean (SD) of 29.1 (6.1) year. The majority of women (81.0%) were between 19 and 35 years of age, 2.5% were younger than 19 years and 16.5% were older than 35 years. More than half of women (55.4%) had high school education or less. Almost three quarters (74.0%) of women had income <5000 JDs. The majority of women were housewives (89.6%). The rate of caesarean section rate was 48.8% (27.2% planned CS and 21.6% emergency CS). Table 1 shows the sociodemographic and maternal characteristics of women. A total of 973 (9.7%) women delivered prematurely. Of total births, 297 (2.9%) were < 1500 grams and 1013 (9.8) were 1500-2499 grams.
The overall stillbirth rate was 9.9 per 1000 total births.

Discussion
Stillbirth rates vary widely between countries. In the current study, the incidence of stillbirth was found to be 9.9 per 1000 live births. This rate is similar to the rate in Lebanon for the year 2015 (9.9) (11). The rate is higher than the rate of 7.81 per 1000 births that was reported in a multi-ethnic Middle-Eastern based study (5), and that was reported for the year 2015 for some other Arab countries such as Libya (8.8 per 1000 live births), Oman (8.5 per 1000 live births), Qatar (5.8 per 1000 live births), and Kuwait (5.1 per 1000 live births) (11). However, the rate was lower than the rate of 11.6 per 1000 live births that was reported in a previous Jordan study in 2012 (8), and the 2015 rates in other countries such Syria (11.1), Saudia Arabia (13.9), Egypt (12.2), Iraq (15.5), and Jordan (10.5) (11). This decline is promising and might be related to improvements in maternal and child health care, yet there remains a room for more improvement. The goal is to reach the rates of other developed countries such as that of the USA (3) or the UK (2.9) (11). In order to achieve such rates, we need to address possible risk factors and possible causes of stillbirths.
Our study showed that low birth weight, preterm birth, and multiple gestation are risk factors of stillbirth. Although risk factors remain not specific until now, these are well known risk factors in the literature and are closely linked to stillbirths (12)(13)(14)(15). Low birth weight may result from both fetal growth restriction and preterm birth, which are associated with placental dysfunction and subsequent poor fetal outcomes (2). This increases the risk of both antepartum and intrapartum fetal deaths (2).
As stillbirth rates are very sensitive to access to high quality antenatal health care (7), proper assessment and early identification of multiple gestations, gestational age, and birth weight may contribute to the decrease of the incidence of stillbirths.
Although advanced maternal age of > 35 years was reported as a significant factor for increased stillbirth rate (16, 17), it was not found to be significant in the current study. The exact mechanism of the increase risk of stillbirth with advanced maternal age is not fully understood (18), which necessitate additional studies to determine the mechanism. However, some research suggested that advanced maternal age is associated with placental dysfunction that may increase the risk of stillbirths (18) or to existing maternal medical condition (19). Nevertheless, of the existed evidence, the lack of relationship in this study between advanced maternal age and risk of stillbirth may be explained by the low percentage of mothers of advanced age in our sample.

13
Based on the WHO ICD-PM classification, the main two fetal causes of antepartum stillbirth in this study were antepartum death of unspecified cause and acute antepartum event, followed by congenital malformations and chromosomal abnormalities. Congenital malformation was reported constantly across many classification systems (7), which could be preventable by prenatal folic acid supplements that is proved to decrease the incidence of congenital abnormalities such as neural tube defects (20).
Complications of placental cord and membranes was identified as the main maternal cause of stillbirth in our study. Previous studies showed that a significant percentage of stillbirths arises from placental problems (16,21). Because of the inadequate oxygen supply to the fetus, placental dysfunction is linked to intrauterine growth restriction, preterm birth, and birth defects (22), which significantly increase the perinatal mortality and morbidity. This explains why preterm birth and low birth weight are the main contributing factors of stillbirths.
Intrapartum stillbirths were relatively few in our study, however, they were significant in highlighting it could be used with high risk pregnancies for the many presumed benefits of it, including better estimation of gestational age, earlier detection of multiple pregnancies, placental abnormalities, fetal malformation and intrauterine fetal restriction (26).
Stillbirth rate is a sensitive indicator of the quality of perinatal care that women receive during their 14 pregnancy. The antepartum stillbirths reflect the quality that women receive during the antenatal period, while the intrapartum stillbirths reflect the quality of care that they receive during delivery (27). The WHO has reported that deficiencies in the quality of antenatal care play significant role in increasing stillbirth rate (28). A wise coverage of basic antenatal care can prevent a significant proportion of stillbirths (29). Afulani reported a decrease in the odds of having a stillbirth by half with a high quality of antenatal care (30). Research has documented a significant decrease in stillbirths with higher quality antenatal care, women education, and regular antenatal visits, and recommended more involvements of the health care provider in teaching mothers about the danger signs of pregnancy rather providing only the basic health care assessments such as measuring their blood pressure (30).
Maternal mortality and stillbirth are strongly correlated. It is imperative, therefore, to increase our attention for stillbirths and preterm birth interventions, which will positively impact on the maternal and newborn health outcomes (31). Investing in the health care system and providing a good quality and timely maternal services may prevent significant ratio of stillbirths (29).

Conclusions
Although the rate of stillbirth is declining and is lower than that in other countries in the region, there is an opportunity to prevent such deaths. While the majority of stillbirths occurred during the antepartum period, care should be taken for early identification of high-risk pregnancies and ensuring adequate antenatal obstetric interventions. Low birth weight, preterm birth, and multiple gestation are reported as risk factors in the current study, therefore, efforts must be directed toward early prediction of these risks so that appropriate and timely interventions may be implemented to reduce stillbirths. This study reported the findings of stillbirths' data extracted from a national neonatal and stillbirth surveillance system. As the majority of stillbirths and neonatal deaths are not reported in Jordan, investing in the health information systems to improve data registration will encourage appropriate use of interventions to reduce stillbirth rates.
Abbreviations JSANDS Jordan Stillbirth and Neonatal Surveillance.

ICD-PM
International Classification of Diseases-Perinatal Mortality.

Ethics approval and consent to participate
The study was ethically approved by the Institutional Review Board (IRB) at Jordan University of Science and Technology (Ethical approval number 20170033). To ensure the data confidentiality, date was exported without identifying information such as the name and phone number.

Consent for publication: Not applicable
Availability of data and material: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests:
The authors declare that they have no conflict of interest.