Risk factors of preterm birth among mothers who gave birth in public hospitals of central zone, Tigray, Ethiopia: unmatched case–control study 2017/2018

Objective The aim of the study was to identify the risk factors for preterm birth in public hospitals of the central zone, Tigray, Ethiopia 2017/2018. Result A total of 88 neonates who born preterm (cases) and 176 neonates who born term (controls) with their index mothers were included making a response rate of 100%. About 84/88 (95.5%) mothers in cases and 173/176 (98.3%) in control had antenatal care follow up. Among them, 33 (39.3%) cases and 102 (58%) controls were had antenatal care follow up four times and above. In multiple logistic regression at P-value < 0.05, mothers with ANC follow up less than four [AOR 95% CI 2.15 (1.19, 3.85)], mothers with pregnancy-induced hypertension [AOR 3.245; 95% CI (1.58, 6.67)], multiple pregnancy [AOR 2.47; 95% CI (1.14, 5.33)], fetal distress [AOR 4.0; 95% CI (1.9, 8.2)] and birth defect [AOR 3.19; 95% CI (1.22, 8.34)] were independent risk factors of preterm delivery.


Introduction
Preterm birth is demarcated as a delivery which occurs at less than 37 completed weeks of gestation or fewer than 259 days [1]. It is classified as extremely preterm (< 28 weeks), very preterm (28 to < 32 weeks), and moderate (32 to < 34 weeks) and late preterm (34 to < 37 weeks) [2]. Preterm birth is a syndrome which can be classified into spontaneous preterm birth and provider-initiated preterm birth [2,3].
Worldwide approximately 15 million babies are born too soon every year as a preterm birth and more than 60% of them were in sub-Saharan Africa and South Asia where health systems are weak in access and minimum health services utilization [4]. Even though there are many different causes of preterm-related neonatal death, greater than 75% of deaths are preventable without the need for intensive care [5,6].
Preterm birth is the biggest cause of neonatal mortality worldwide and the second leading cause of underage five child deaths following pneumonia [4,7,8]. The incidence rates of preterm delivery were highest in Africa and North America, 11.9% and 10.6%, respectively [9].
There is an intense survival gap for premature babies depending on where they are born [3,10]. Preterm birth is becoming the cause for economic instability in the family, community and the nation at large. It is not only resulted in economic burdens due to initial neonatal treatment but also in substantial costs to health services after discharge from the neonatal unit [3].
Being born preterm is a risk factor that put infants at higher risks of chronic diseases and death later in life [11]. Babies born preterm have continued to remain below the standard growth curve and demonstrate the reduced ability for catch-up growth in their life [12]. Moreover, preterm delivery and its consequences contribute to  [2,12,13].
Socio-demographic factors, obstetric and gynecological-related factors, maternal medical disorder and common medical problems in neonates were some of them [9,[14][15][16]. Additionally, high levels of preterm birth in Africa are also possibly presented due to intrauterine infection or lack of availability of drugs, like Tocolytic agents [1].
Global progress for child survival and health cannot be achieved without addressing preterm birth [15]. This paper is important for policymaker by giving important information related to preterm birth to give intervention for prevention.
Despite the increase in ANC coverage and recommended guidelines for maternal and neonatal care, the number of preterm birth is increased through time. Even if there are limited studies which show the risk factors of preterm birth through the card review in some part of Ethiopia, the risk factors are different in different settings because of the difference in the healthcare system and demographic features. Consequently, this study was aimed to identify the risk factors for preterm birth in the central zone of Tigray.

Study area and period
The study was carried out in public hospitals of central zone Tigray, which has three hospitals named as St. Marry Hospital, Adwa Hospital, and Abyi Adi Hospital. We include 25 cases and 50 controls in Abyi Adi Hospital, 30 cases and 60 controls in Adwa Hospital and 33 cases and 66 controls in St. Marry Hospital. Data collection period was undertaken from December 2017 to February 2018.

Study design
A hospital-based un-matched retrospective case-control study design was employed.

Source population
All mothers who gave birth in public hospitals of the central zone of Tigray.

Study population
For cases All mothers with alive PTB (28 to < 37 weeks) in public hospitals of the central zone of Tigray.
For controls All mothers with full-term birth (≥ 37 weeks) at the same hospitals.

Sample size and sampling technique
A double population proportion formula (stat calc EPI info 7.1.1) was used with 95% confidence level, 80% power and proportion of controls with exposure of previous history of preterm birth 36.36% [17], odds ratio 2.25 and case to control ratio were 1:2. The final sample size with adjustment for non-response rate of 10% was 264 (88 cases and 176 controls). Systematic sampling technique was used every two intervals in both cases and controls. The first participant was selected by lottery method. Confirmation of preterm birth admission was taken from the documentation and information from the staffs.

Data collection tools and procedures
Data was collected using interviewer-administered pretested semi-structured questionnaires and data recorded. The questionnaires were taken from different related studies [3,[16][17][18] and necessary modifications were done to be applicable to the current study and population. A translated Tigrigna version questioner was used to collect data. Four B.Sc. Nurses for data collection and two MSc nurses for supervisor were recruited.

Data quality control
Training was given for data collectors and the questionnaires were pretested on 5% of the sample size at Suhul Hospital prior to the data collection period. Continuous follow-up and supervision were made by the supervisor and principal investigator. All participants were interviewed privately.

Study variables Dependent variable
• Preterm birth.

Independent variables
• Maternal socio-demographic factors, gynecologic and obstetric related factors, maternal medical history of disorders, maternal emotional stress, infant's characteristics. Those information was obtained by face to face interview and record files.

Operational definitions
Preterm birth Those who born in < 37 weeks.

Plan for data processing and analysis
The data was cleaned, entered and edited using EPI-DATA version 3.1 statistical software, then exported to SPSS Version 22.0 for analysis. Results were presented using tables and texts. Hosmer-Lemeshow test was used to check the appropriateness of the model for analysis. Variables which were show statistical significance during bivariate analysis at P-value ≤ 0.25 were entered to multivariable logistic regression. Adjusted odds ratios (AOR) with 95% CI, were estimated to assess the strength of associations and statistical significance was declared at a P-value < 0.05.

Socio-demographic characteristics of respondents
In this study, all the study participants were accepted to be part of the study which includes 88 preterm neonates (cases) and 176 term neonates (controls). The mean (± standard deviation) age of mothers was 27 ± 6 years' ranges from 17 to 45 years. Most of the respondents 80 (90.9%) cases and 166 (94.3%) controls were orthodox. Regarding marital status, 79 (89.8%) cases and 161 (91.5%) of controls were married. About 60 (68.2%) of cases and 131 (74.4%) of controls were housewives by occupation and 25 (28.4%) cases and 46 (26.1%) of controls were not able to read and write (Table 1).

Risk factors associated with preterm birth
In the bivariate logistic regression at 25% level of significance, number of ANC follow up, maternal height, birth defect, fetal distress, PROM, multiple pregnancies, pregnancy-induced hypertension were statically significant with preterm birth. In multiple logistic regression at P-value < 0.05 using backward elimination method, mothers with ANC follow up less than four were two times more to give preterm birth than those who had greater than or equal to four ANC follow up (AOR 95% CI 2.15 (1.19, 3.85). Mothers with pregnancy-induced hypertension were about three times higher to give preterm birth than those who had no hypertension [AOR 3.245; 95% CI (1.58, 6.67)]. The odds of a mother with multiple pregnancies were about two times more to give preterm birth than mothers with single pregnancy [AOR 2.47; 95% CI (1.14, 5.33)]. Neonate with fetal distress during labor and delivery were about four times higher to be preterm than those who had no fetal distress [AOR 4.0; 95% CI (1.9, 8.2)] and those who have birth defect were about three times higher to had a chance of preterm birth [AOR 3.19; 95% CI (1.22, 8.34)] (Table 3).

Discussion
The study was aimed to assess the risk factors for preterm birth in order to tackle the burden of the disease and its associated problems.
The lack of ANC diminishes the chance of identifying risks and provide appropriate interventions towards prevention of preterm delivery. Our finding revealed that women who follow ANC less than four times were about two times more to give preterm delivery as compared to women who attended ANC four times or more. This is consistent with the study done in Tanzania [20], Debremarkos Town Health Institution [17], western China [21], Gaza strip [22] and south-western Nigeria [23]. This could be due to the fact that women with regular ANC follow up may have more chance to early detection of severe diseases or obstetrics complications and appropriate case management. The regional government should enhance the awareness of women in ANC follow-up by increasing community ownership through women development army.
Our study revealed that mothers who had pregnancy induced hypertension had three times increased the risk of having a preterm birth than those mothers without pregnancy-induced hypertension. This finding is in line  with studies conducted in Gondar [16], Debremarkos [17], southern India [19], western China [21] and southwestern Nigeria [23]. This could be due to hypertension decreases the uteroplacental blood floor which leads to intrauterine growth restriction that causes preterm delivery. The other reason might be due to complications of pregnancy-induced hypertension can cause vascular damage to the placenta, which induces the oxytocin receptors, results in preterm labor and delivery. We found that mothers with multiple pregnancies had more than twofolds increasing the likelihood of having preterm delivery as compared to mothers with singleton delivery. This is consistent with the study done in Tanzania [20], south-western Nigeria [23]. Palestine [24], southern India [19], Gaza strip [22]. This is probably due to multiple pregnancies could over distend the uterus which stimulates early labor leading to preterm delivery.
In our finding the likelihood of preterm delivery among birth defect neonate were three times more significant than those who had no any birth defect. This could be due to the interaction of genetic and environmental risk factors contribute to preterm delivery. Identification of specific modifiable risk factors should be an important research and public health priority.
In this study, we find that fetal distress was about four times more significantly associated with preterm delivery. This finding is consistent with the study done in Jakarta [25]. Fetal distress infant could medically indicated to premature births as emergency births, where the decision to deliver must be made very quickly. Pregnancy-induced hypertension may decrease blood flow from mother's placenta which leads to hypoxemia in the fetus. This condition can lead to fetal distress.

Conclusion
The commonest obstetrical risk factor for preterm birth was hypertensive disorders of pregnancy and multiple pregnancies. Regarding to neonates, fetal distress and birth defect were the significant variables with preterm delivery. Early detection and treatment of diseases or disorders among pregnant women as well as the improving health care quality delivered to pregnant women may reduce risk factors for preterm delivery.

Limitation
Our study is limited to hospital-based quantitative study. It would be better if qualitative approach study was triangulated to investigate further factors on preterm birth.