In the present study, we reported stillbirth cases over a 12-month period of the pilot implementation of a new registration system in 14 hospitals. According to the ReCoDe classification, in 742 cases of stillbirth in 14 selected hospitals, the relevant causes were identified in 65.4% of cases, while 34.6% of cases remained unclassified. The most frequent relevant conditions were fetal (33.2%), maternal (9.1%), amniotic fluid (8.8%), placenta (7.7%), and umbilical cord (6.2%). Our registration decreased the percentage of stillbirth with an unknown cause from about 70% in the nationwide IMAN to 34.6%.
Based on other studies, 15% to 20% of stillbirths are associated with congenital anomalies (10). Our results indicated a frequency of 19.3% for congenital anomalies. Such cases may be reduced though preconception consultation and tests, antenatal care, prenatal diagnostic testing, and pregnancy termination (10). A retrospective cohort study of 65,308 singleton pregnancies showed that isolated critical congenital anomalies increase stillbirth risk up to 15 times (11). Close and regular monitoring are recommended for mothers at higher risk due to special medical conditions. According to proclamation number 302/25013, dated November 8, 2011, issued by the Iranian Ministry of Health and Medical Education, screening tests for fetal disorders (including chromosome abnormalities and neural tube defects) must be recommended to pregnant women (12). Due to the high prevalence of congenital anomalies in our study, we recommend programs to provide optimal prenatal care for all mothers, especially those with low socioeconomic status and lower education levels. We recommend free-of-charge or subsidized screening services as the most effective prenatal measures to identify congenital anomalies and chromosome abnormalities.
As intrauterine growth retardation is a common cause of stillbirth, it may be considered a suitable target for reducing the frequency of stillbirths (13, 14). This study defined it as estimated fetal weight (EFW) below the 10th percentile (15).
Sonographic assessment of intrauterine growth must be considered for at-risk patients. Fetal growth charts may help identify intrauterine growth retardation cases and distinguish them from constitutional cases (15). Therefore, serial sonographies are recommended in these cases (16-18).
Our study found about 34.6% of stillbirths to be unexplained. Based on other studies, this is incredibly challenging, as it hinders the development of effective strategies for preventing stillbirths(19). According to our findings, 51.2% of stillbirths occurred after week 28, among which about 32% were unexplained stillbirths. Unexplained stillbirths constitute the largest category of relevant conditions among stillbirths after week 28, followed by malnutrition and placental abruption. One cohort study investigated the risk factors associated with unexplained stillbirths from 1978 to 1996. The risk factors included higher maternal age (40 years or more; OR=3.7, 95%CI: 1.06 to 1.3), a lower maternal education level (OR=2.5, 95%CI: 1.1 to 5.5), the birth weight ratio between the 2.4th and 10th percentile (OR=2.8, 95%CI: 1.5 to 5.2), and birth weight ratio over the 87th percentile (OR=2.4, 95%CI: 1.3 to 4.4) (20).
Considering all influential factors of stillbirth, developing an interactive model may be beneficial for estimating the risk of stillbirth, similar to models used for estimating the risk of myocardial infarction and mortality due to cardiovascular risk factors. Risk analysis must guide management policies and provide an evidence-based approach to choose the accurate antepartum tests and induction of labor (21). It must be noted that autopsy, placental examination, and genetic tests may reveal the etiology of stillbirth in many of the unexplained cases (22).
Maternal Risk Factors:
Maternal risk factors were the relevant causes of about 9% in this research. Gestational diabetes and hypertensive disease in pregnancy were the most common conditions. Hypertension and diabetes are two common risk factors that impose higher risk to pregnancy (7%-10% and 3%-5%, respectively) (21). Placental insufficiency and abruption are among the most critical causes of stillbirth in mothers with hypertensive disease. Adequate control of blood pressure, eclampsia, and pre-eclampsia may lower stillbirth risk, although premature delivery frequently occurs (23). Historically, these two factors account for a large number of stillbirths, but ideal management incorporating preconception care and consultation has reduced stillbirth in these cases (24). Nevertheless, such patients are often challenging as they are more susceptible to placental abruption, intrauterine growth restriction, and pre-eclampsia. There is limited data on the cost-effectiveness of interventions targeting stillbirth. As discussed before, medical risk factors have a considerable impact on mothers' and children's health; therefore, appropriate medical care and preconception consultation may profoundly affect pregnancy outcome. Care providers are recommended to perform a risk assessment on an individual basis. Screening for hypertension and diabetes is necessary to prevent unfavorable pregnancy outcomes; furthermore, other factors such as advanced maternal age, prepregnancy obesity, infertility, and low education level (as an indicator of low socioeconomic status) must be incorporated in all risk assessments (21).
Advanced maternal age is an independent risk factor for stillbirth. Even after adjusting for risk factors such as multiple pregnancies, hypertension, diabetes, previous miscarriage, and placental abruption, which are more common in older women, maternal age remains an independent risk factor. Advanced maternal age is associated with preterm delivery, fetal abnormalities, and fetal growth restriction (25).
In addition, women aged 35 years or more are at higher risk for stillbirth associated with congenital anomalies (26). With the advent of prenatal diagnostic tests and the possibility of deliberate abortion, these rates have been declining. Longitudinal studies indicate that fetal death with anomalies after week 20 has been gradually replaced by deliberate termination of pregnancy before 20 weeks of gestation (10, 27).
Placental abruption was the relevant cause of 4.7% of stillbirths in our study. Placental abruption occurs in almost 1% of pregnancies, but it accounts for some 10% to 20% of stillbirths (28). The risk of fetal demise amounts to over 50% when the placenta disintegrates or when the placenta's central part is involved. Therefore, the placenta's gross and microscopic examination should be considered an integral part of stillbirth assessments (29).
Umbilical cord abnormalities accounted for 10% of fetal deaths in a population-based study (28). Almost like our study, umbilical cord abnormalities were responsible for 6% of stillbirths. An umbilical cord knot may provide an immediate, potential explanation of fetal death for the physician and the patient; nonetheless, death should be attributed to the umbilical cord knot only after a comprehensive search for other causes and when other findings corroborate this diagnosis (28).
In our study, we benefited from a large sample size from different geographical part of Iran. This study was one of the first study that registered related causes of stillbirth in our country. But we have some limitations for example missing data on some variables and our data base for registering stillbirth had limitation for uploading photos of dead fetus add screenshots of lab data. Only 6 photos could be uploaded. In cases where more photos were needed, the photos were sent to the research team via WhatsApp.