Assessing the risk factors of preterm births in Kurdistan, Iran: a case-control study

Preterm birth is one of the most common causes of mortality in infants. Despite advances in health care and better access to health services in many countries, preterm birth has increased over the past two decades. This case control study was conducted on two groups with 100 participants including 100 preterm infants (case) and 100 term infants (control) with gender match in Kurdistan Province-Iran in 2018. The required information was collected from medical les and interviewing the mothers as to demographical information, midwifery specications, background diseases, disease over pregnancy term, and infants’ information. Conditional logistic regression test was used to estimate the nal model and compute the risk ratio. Multivariate regression analysis showed that the risk of preterm birth in individual with AB blood type was higher (OR=5.04; 95% CI 1.40-18.08). In addition, the risk of preterm birth was higher in the with a history of stillbirth (OR=13.63; 95% CI 1.39-133.5). Preterm birth was signicantly related to the of pregnancy and using medicine for specic diseases during pregnancy.

increase in preterm birth. Therefore, it is essential to have a deeper insight into the risk factors of preterm birth. The present study is an attempt to examine the risk factors of premature birth in Kurdistan Province-Iran.

Data source
A case-control study was carried out on two groups of preterm infants (n = 100; case) and term infants (n = 100; control) in Besaat Hospital, Sannadaj-Kurdistan (2018). The participants were selected through census sampling. Inclusion criterion in the case group was women with pregnancy age less than 37weeks and in the case of control group, women with pregnancy age of more than 37weeks. The two groups were homogenized in terms of infants' gender. The information was gleaned from medical les and interviewing the mothers in ve areas of demographics, midwifery speci cations, background diseases, pregnancy diseases, and infant information. Individuals with a history of intrauterine fetal death (IUFD), abortion, psychological, systemic, and metabolic diseases were excluded. All participants were informed about the purpose and process of the study, and written informed consent for participation in the study was obtained from the participants. The approval for this study was obtained from the Ethics Committee of Kurdistan University of Medical Science (IR.MUK.REC.1398.051).

Statistical analysis
Frequency and percentage of each one of the variables were calculated for the both groups and the relationship between qualitative and quantitative independent or depended variables was examined using chi-square and t-tests. To obtain the nal model, the variables with P<0.20 were examined using univariate logistic analysis and adjusted odds ratio (OR) was obtained using conditional logistic regression.P < 0.05 was considered statistically signi cant. All statistical analyses were performed using Stata14.0 software (StataCorp, College Station, TX).

Results
As the results showed, 71% and 78% of the case and control groups were city dwellers respectively and 12% and 21% of the case and control groups had a college degree respectively. Cousin marriage in the case and control groups were 13% and 19% respectively. Frequency of the history of smoking or exposure of cigarette was higher in the case group than the control group.
Spiritual and mental tensions in the case group was higher than the control group. Frequency of blood type in the case and control groups was different; so that the highest and lowest frequencies of blood type in the two group were O and AB respectively (P<0.001(. Frequency of stillbirth in the case and control groups were 8% and 1% respectively (P = 0.017).
Background diseases (diabetes, hypertension, epilepsy, anemia, urinary infection, hyper/hypothyroid, mouth and teeth problems, etc.), pregnancy disease (history of pregnancy bleeding, uterus anomaly, pregnancy diabetes, vaginal bleeding during the third three months, cardiac disease during pregnancy, renal disease during pregnancy, polyhydramnios, history of alkilo hydramnios, and history of trauma) in the case group was signi cantly higher than the control group (P = 0.048). More than 95% of the case and control groups used pharmaceutical supplements ( Table 1). The results about the other quantitative variables like number of pregnancies, number of term births, number of abortions, BMI, birth order, and mother's hemoglobin level are listed in Table 1.
The results of univariate analysis showed that the risk of preterm birth in mothers with AB blood type (OR = 5.36; P = 0.003) was higher. In addition, the risk of preterm birth was higher in the mothers with a history of stillbirth (OR = 8.60; P = 0.016), mothers with a history of background disease (OR = 1.99; P = 0.017), mothers with pregnancy disease (OR = 175; P = 0.048), mothers with a history of multiple pregnancy (OR = 38.5; P<0.001), mothers who used medicine for a speci c disease (OR = 1.69; P = 0.001); and mothers with a history of premature birth (OR = 3.08; P = 0.012) ( Table 2). The multivariate regression analysis showed that the risk of preterm birth in women with AB blood type was higher than other blood types (OR = 5.04; 95% CI 1. 40-18.08). In addition, the risk of preterm birth in the mothers with a history of stillbirth was higher (OR = 13.63; 95% CI 1.39-133.5). The risk of preterm birth was higher in mothers with a history of pregnancy diseases (OR = 2.27; 95% CI 1.07-4.21) and the mothers who used medicine for speci c diseases during pregnancy (OR = 3; 95% CI 1.24-6.25). The risk of preterm birth in women with a history of premature birth was higher in the case group (OR = 4.06; 95% CI 1.44-11.49) ( Table  2).

Discussion
Preterm birth was signi cantly related to the history of stillbirth, blood type, history of premature birth, mother's diseases, and using speci c medicines during pregnancy. Although, advances in pediatric medicine and novel methods of infant care have increased the survival chance of preterm infants, the rate of preterm birth has remained almost unchanged and a serious challenge for health system.
The risk of preterm birth in women with a history of stillbirth was higher in the case group comparing with the control group. Soltani et al. showed that the risk of preterm birth in women with a history of stillbirth was four times higher than women without it [1]. Malacova et al. reported that the risk of preterm birth in women with a history of stillbirth was three to four times higher. They also showed that the risk of preterm birth in these women had increased by 10times [13]. A study by Abu Hamad et al. showed a signi cant relationship between the history of stillbirth and preterm birth [14].
The results showed that the risk of premature birth in the mothers with a history of preterm birth was higher in the case group comparing with the control group. A study in Gaza Strip showed that there was a signi cant relationship between the history of preterm birth and premature birth in the next pregnancy [15]. Abaraya et al. reported that women with a history of preterm birth had a higher risk of preterm birth comparing with mothers without any history of preterm birth and the difference was signi cant [16]. Results of other studies have shown that the history of preterm birth has a signi cant relationship with preterm birth [17][18][19][20].
Distribution and diversity of ABO blood types depends on ethnicity, race and geographical region. For instant, the most common blood type in European countries and Japan is A and in the USA is O [21]. The ndings showed that the participants with AB blood type in the case group had the highest risk of preterm birth comparing with the other blood types. This nding is inconsistent with [21,22]. The differences in the nding might be due to sample groups, ethical differences, and demographical differences [21].
The mothers who used speci c drugs due to a disease in pregnancy had a higher risk of preterm birth. Li et al. showed that the risk of preterm birth in mothers who used hormonal drugs (OR; 2.23), blood pressure drugs (OR:7.74), and other medications (OR:2.15) during pregnancy was higher than those who did not use any medicine during pregnancy. This nding is consistent with our ndings [23]. A meta-analysis study showed that the risk of preterm birth in the mother who used antidepressants (OR:1.16) during pregnancy was higher than other women [24]. A study by Huang et al. showed that mothers who used antidepressant had a higher risk of preterm birth (OR:1.69) [25].
The risk of preterm birth in the mothers with a history of pregnancy diseases was higher. A metanalysis based on population in 2007 showed that the risk of preterm birth in women with in ammatory bowel disease (IBD) was 1.87times higher than healthy mothers [26]. A study in Asia reported that the risk of preterm birth in mother with IBD was higher [27]. Several studies have shown that mothers with hypertension have a higher risk of preterm birth comparing with healthy women [18,[28][29][30][31][32][33]. In addition, the risk of preterm birth in mothers with diabetes and those who did not give diabetes tests during pregnancy was higher than the mothers without diabetes [31][32][33][34]. Sibai et al. reported that the risk of preterm birth before the 35 th week in women with and without diabetes was 9% and 4.5% respectively-i.e. diabetes is a risk factor of preterm birth [35]. A study by Roozbeh et al showed that urinary ducts infection during pregnancy (35.8%) and PROM (30.3%) were among the effective risk factors in preterm birth [36]. The results showed that there was a signi cant relationship between mother's disease (e.g. diabetes, hypertension, UTI, PID, and nutritional anemia) and preterm birth [15,37]. Other studies have shown that the sideeffects and diseases like eclampsia and placental abruption are among the risk factors of preterm birth [38,39]. In general, premature birth is related to the side-effects of pregnancy such as placental bleeding, higher blood pressure in pregnant women, and preeclampsia as these factor limit intrauterus development [40]. In addition, the side-effects of pregnancy hypertension may damage placental veins and stimulate oxytocin receptors, which leads to preterm delivery. Other disease like urinary ducts infections weaken amniotic membrane around the embryo and this leads to PROM and preterm birth [41]. Because these associations were inconclusive, we did not consider these factors in our study. Due to the above mentioned limitations, further studies are required for causality between risk factors and preterm births and increase sample size.

Conclusion
Mother's blood type, history of stillbirth, pregnancy disease, history of preterm birth, and history of using medicine due to speci c pregnancy disease were the risk factors of preterm birth. These factors need to be taken into account in prepregnancy and pregnancy health cares. Through this, the health systems can lower the rate of preterm birth and mortality in mothers and infants. Knowing that preterm birth is a multi-cause phenomenon, identifying the risk factors and screening the mothers with such risk factors is a way to convince mother to participate in controlling the effective variables and preparing for preterm birth. These measures lead to a lower rate of preterm and premature birth and mothers and infants' mortality in return. In addition, the majority of the factors in preterm birth are unpredictable and unavoidable; therefore, provision of health services and facilities for emergency services to these mothers and infants is essential.