In this historical cohort study conducted among 18129 hospital records, the following results were reached: the cumulative incidence rate of stillbirth was 9.48 per 1000 live birth. Among maternal causes, gestational hypertension was identified as the first risk factor associated with increased risk of stillbirth. The findings also showed that gestational diabetes was the other risk factor for stillbirth, which increased the risk by twofold. Pregnant women with hypothyroidism were twice more likely to have stillbirth than healthy pregnant women. Amongst fetal causes, male gender increased the risk of still birth by more than threefold. Fetal disease (i.e. IUGR, congenital anomaly, chromosomal disorder, oligohydramnios, polyhydramnios, brain disorder and severe hydrops) was identified as the other main predictor of stillbirth, which increased the risk by threefold. For the first time, maternal hypothyroidism, oligohydramnios and polyhydramnios were shown as risk factors for stillbirth, which were not evaluated in any previous study.
The findings of this study showed that the cumulative incidence of stillbirth was 9.48 per 1000 live birth. In a study conducted by Tshibumbu et al., 2014 in Namibia, the rate of stillbirth was reported as 12 per 1000 births , and the incidence of the stillbirth in hospital in few months was 8% or 80 per 1000 births . However, Blencowe et al., 2016 estimated the rate of stillbirth as 23 per 1000 live births in India . Our estimates of stillbirth incidence was much lower, which can be due to racial, environmental, and socioeconomic differences or variations in data collection methods.
In addition, Neogi et al., 2018, Newtonraj et al.,2017, Ashish et al.,2015, Liu et al.,2014, Al-kadri et al.,2012, Mutihir et al.,2010, concluded that gestational hypertension was one of the factors associated with stillbirth, which was in line with the results of our study [21-26]. Gestational hypertension increases the risk placenta to be separated earlier by twofold, leading to fetal-growth disorders, by increasing the risk of maternal mortality by threefold .
Furthermore, gestational diabetes mellitus was shown to be significantly associated with stillbirth, which is consistent with the systematic review of Liu et al., 2014, indicating that gestational diabetes mellitus increased the risk of stillbirth by 2 to 5 folds. This was also supported by the results of Kean et al., 2009, Casson IF et al.,1997, Dunne F et al., 2003, Dunne FP et al., 2009, [26,28-31]. Birth weight greater than 4000g is shown to increase the rate of stillbirth in diabetic mothers . There is evidence that fetus of diabetic mothers classified as large for gestational age, is at greater risk of stillbirth . Even with a strong efficient patient monitoring system, women with gestational diabetes mellitus are still at high risk for stillbirth . In fact, certain increase in blood glucose level or a sudden onset of diabetes mellitus in the third trimester of pregnancy might lead to fetal death .
In addition, it was concluded that hypothyroidism could lead to stillbirth, which was consistent with the results of Liu et al., 2014, and other previous studies [26,36-38]. This is justifiable, since endocrine disorders (thyroid dysfunction) occurs mainly in women, and its prevalence amongst women in Shiraz, is high . Azizi et al., concluded that maternal hypothyroidism during pregnancy leads to placenta abruption, prematurity and low birth weight, intrauterine growth restriction, congenital malformations and stillbirth . In addition, thyroid disease is very common in Iran, especially among women, and many women of childbearing age who have hypothyroidism are unaware of their illness . Chen et al., 2014 proposed that hypothyroidism leads to IUGR, hypertension and premature rupture of membranes .
Rate of stillbirth amongst male gender is 3 times higher than females, which is supported by Mutihir et al., 2010, and male gender is two times more likely to have stillbirth . This can be due to higher susceptibility of the male gender in the embryonic period, as well as higher rate of male birth [43-48].
Novelty, according to the findings of this study, fetal diseases (IUGR, congenital anomaly, chromosomal disorder, oligohydramnios, polyhydramnios, brain disorder and severe hydrops) were associated with increased risk of stillbirth by threefold, which was consistent with results of Patel et al., 2014, Newtonraj et al., 2017, Kean et al., 2009, and Liu et al., 2013 [28,36,40,49]. It should be noted that for the first time, maternal hypothyroidism, oligohydramnios and polyhydramnios were shown as risk factors for stillbirth, which were not evaluated in any previous study.
Importantly, in the present study, Univariate analysis without considering the confounding effect of some covariates such as maternal age, mother’s blood group, number of abortion and fetal weight were shown to be associated with still birth. However, after taking into account the confounding effect, these variables did not remain as risk factor. Therefore, interpretation of the result without considering the confounding effect would be misleading.