In 42 cases of autopsy, based on ReCoDe classification, related causes of 95.2% of stillbirths identified and 4.8% were in the unclassified group. The most common causes were: Fetal causes (64.3%), umbilical cord (14.3%), placenta (7.1%), amniotic fluid (4.8%), and maternal medical conditions (2.4%). Among the fetal causes, the most common associated conditions were lethal congenital anomaly (35.7%), fetal growth restriction (16.7%), and non-immune hydrops (4.8%).
According to the results, this study has performed better in identifying the causes of stillbirth in Iran compared to previous studies.
We have an integrated maternity care program in Iran which includes pre-pregnancy (one care annually), prenatal care (8 cares) and postpartum (3 cares). These services are performed in health care centers by health care providers. These services are free for everyone [15].
A population-based cohort study of 2,625 stillbirth cases in West Midlands compared two classification systems: Wigglesworth and ReCoDe [12]. Wigglesworth is a simple pathophysiological classification of perinatal mortality which assigned death to one of five categories. This classification is reproducible and can be used without autopsy [16]. 66.6% of stillbirths were unexplained using the Wigglesworth classification, whereas only 15.2% of cases were unexplained using the ReCoDe classification [12]. Therefore, it seems that the use of ReCoDe system greatly reduces the unexplained.
Congenital anomaly
The rate of congenital anomaly among stillborn varies from country to country [17]. Major anomalies are responsible for 15% to 20% fetal death [18]. A retrospective cohort study of 65,308 singleton pregnancies showed that major congenital anomalies increased the risk of stillbirth by 15-fold and even fetal growth restriction was related with a higher rate of stillbirth [19].The Ministry of Health and Medical Education has recommend screening tests including congenital anomalies and neural tube defects for all pregnant women, since 2011 [20]. This sample is not representative for all stillbirth cases, however due to the high rate of congenital anomalies in our study (35.7%), it is recommended to assess cost-effectiveness of these screening tests.
Fetal growth restriction
Fetal growth restriction observed in about 17% in our research. It is well noted in literature that a considerable percentage of stillbirths is related to fetal growth restriction [21]. The risk of stillbirth in pregnancies with unrecognized fetal growth restriction increased over eightfold in comparison to pregnancies without fetal growth restriction [22].
Recognizing fetal growth restriction before birth is important in preventing stillbirths. Therefore, sonographic evaluation of fetal growth must be considered for all high risk patients [23].
Death at earlier gestational age (GA) is associated with congenital anomalies, intra-uterine growth restriction, and maternal medical conditions. On the other hand, at more advanced gestational ages, maternal medical conditions, obstetric disorders (such as placental abruption, placenta previa, umbilical cord prolapse, and marginal umbilical cord insertion) and unexplained causes are more frequently associated with stillbirth [24]. This was compatible with our study. About 52.4% of our stillbirth occurred at early fetal stage (22–28 weeks).
Cord abnormalities
In this study umbilical cord abnormalities was present in about 14% of stillbirth cases. Hammad et al. evaluated 496 stillbirths and 94 (19%, 95%CI: 16–23%) of them had umbilical cord abnormality [25]. Stillbirths associated with umbilical cord abnormalities reported in 2.5 to 19% of cases in other researches [26,27,28,29]. So the results of these studies are consistent with our study.
Placental abnormalities
To assess the causes of stillbirth, researchers in a retrospective cohort study in Italy examined 132 stillbirths from 2000 to 2004 with autopsies and placental examinations. The data were classified based on the ReCoDe system. The related cause of 79.84% identified and 20.16% were in the unclassified group. However, placental insufficiency, which occurs both in early and late stage of pregnancy, has been associated with intrauterine growth retardation. The most common secondary cause was placental abnormalities [30]. In our study placental abnormality responsible for 50% of secondary causes. Literatures confirmed that a significant percentage of stillbirth is related to placental pathology. Post-mortem examination of placenta by the skilled pathologist help to investigate the cause of stillbirth [31,32,33].
Accurate fetal autopsy along with placental examination and clinical information is essential for the assessment of stillbirth and can reduce unexplained cases of stillbirth [30], however lack of different resources (clinical and pathology experts, laboratory and financial resources) is the main barrier for using this approach for all cases of stillbirth. In a cohort study from 2009 to 2013 at a third level center, Miller et al. assessed 144 stillbirths step by step. Of these, 104 cases (72%) were dissected. Laboratory and clinical findings alone identified the cause of death in 35 cases. In the next step, placental pathology tests identified the probable cause of death in 61% of cases, and with the addition of autopsy, the possible causes of 74% of stillbirths were diagnosed [34].
Iranian Maternal and Neonatal Network (IMaN), registers almost all births (live & dead) electronically across the country [9]. This network recorded the relative conditions of stillbirth based on ReCoDe, but it is adjusted and it does not have enough details and it is not perfect. We still do not have the necessary resources in Iran to collect the necessary data in this field. It is noteworthy due to the fact that more than 70% of the causes of stillbirth in Iran are unknown (based on unpublished IMaN reports) [35], most of the relevant conditions are recognizable thorough review of clinical records, in addition to a simple x-ray and photography. Current system has many caveats, many of the causes would be recognizable with training and establishment of a registration system, and then we need a protocol for doing autopsy for some of the remaining unexplained cases. A review study showed that the autopsy can lead to a change in diagnosis or additional findings in 22 to 76 percent of perinatal deaths. In addition, if the confirmation of clinical findings is added, the value of autopsy can reach 100% [36].
The strength of our study was the use of autopsy report for finding related condition of stillbirths, which increased the accuracy of the results. We have some limitations such as small sample size, and missing data on some variables. In Iran, there is no defined system for which cases to be autopsied. On the other hand, we have limited resources and the centers that perform autopsies for stillbirths. Referral autopsies are performed with the consent of the family. Therefore, our sample was not representative. Another limitation was the use of the ReCoDe, which may not always distinguish between related conditions/risk factors and documented causal association.