Background: The most important digestive system diseases implicated in pregnant mothers’ stillbirth and neonatal death include large intestine diseases, Crohn’s disease, ulcerative colitis, and stomach problems. This study aimed to determine the relationship between digestive system diseases in pregnant women and stillbirth and neonatal death. Methods: This population-based case-control study was conducted on 3573 mothers (1223 mothers experiencing stillbirth, 1091 mothers with neonatal death, and 1259 mothers with live births) in 10 provinces of Iran. The study data were analyzed using logistic regression analysis. Results: A total of 461 pregnant women (12.9%) suffered from digestive system diseases before the last pregnancy among whom 171 women (14.1%) experienced stillbirth, 149 (13.7%) reported neonatal deaths, and 141 women (11.2%) were in the control group. The results showed that the women with digestive system diseases were more likely (32%) to experience stillbirth when compared to those with no digestive system diseases (odds ratio [OR]: 1.32; 95% confidence interval [CI] [1.008 − 1.74]). Neonatal mortality was also higher (58%) among the mothers with digestive system diseases as compared to the control group (OR: 1.58, 95% CI [1.19 − 2.09]). Conclusion: Pregnant mothers with digestive system diseases were exposed to higher risks of severe prenatal consequences. The odds of stillbirth and neonatal death, were, respectively, 0.32 and 0.58 times higher in the pregnant mothers affected by digestive system diseases than those without such problems. This shows the undesirable effects of digestive system diseases on the fetus. Mothers’ knowledge of appropriate nutrition and digestive system diseases has to be improved to prevent these consequences.
Keywords: Case–control, digestive system diseases, neonatal death, pregnancy, stillbirth
Neonatal death and stillbirth are among the important indices of society’s health which are related to socioeconomic status, availability of health-care services and quality of life, etc., Thus, establishing, keeping, and promoting the health of newborns as a vulnerable group are of great importance in the health and treatment services. Although the neonatal period is predicated as the first 28 days of a baby’s life, embryonic life, and neonatal period are in line with each other in growth and development of an individual and are affected by genetic factors and the environment inside and outside the uterus. Other factors, such as social, economic, and culture that influence mothers’ health are also effective in this period.,
Nearly 5.75 million neonatal deaths, or 42 deaths/1000 live births, are reported annually. Furthermore, 3.3 million cases of stillbirth are reported yearly of which 97% occur in developing countries. About 1 or 2 million stillbirths might have also occurred, but were not reported. According to the World Health Organization reports the highest rate of stillbirth was reported from Pakistan with 47 cases in 1000 live births, whereas the lowest rate was related to Finland and Singapore with 2 cases in 1000 live births. In Iran, this rate was estimated to be about 13/1000 live births. The number of reasons has been attributed to difference reported in the developing and developed countries. In developed countries, the most important risk factors of stillbirth, especially delayed stillbirth, included smoking, lack of attention to care during pregnancy, decrease in embryo’s movement, primiparity, obesity, and mother’s old age. On the other hand, the most common risk factors of stillbirth in developing countries included lack of prenatal cares, lack of skilful midwives during the delivery procedure, low socioeconomic status, poor nutrition, history of stillbirth, and older ages at pregnancy. Besides, 65% of stillbirths in developed countries were as a result of old ages during pregnancy.,,,,, In low-income countries, however, infection was responsible for 50% of stillbirths. According to the existing statistics, 4 million out of the 130 million neonates born each year die in <1 week. In fact, more than 10000 newborns die every day and neonatal mortality comprises of 38% of the total mortalities in below 5-year-old groups. Moreover, 99% of neonatal deaths occur in developing countries, 50% of which occur in 4 countries, namely, India (27%), China (10%), Pakistan (7%), and Nigeria (6%). In order to reduce stillbirth and neonatal mortality, pregnant women’s conditions have to be taken into account. Digestive system diseases are one of the important factors in this regard. The most important digestive system diseases in mothers which play a role in stillbirth and neonatal death include large intestine disorders, Crohn’s disease, ulcerative colitis, and stomach problems. Besides digestive diseases, nausea, vomiting, the feeling of irritation in the stomach, and constipation are known as women’s most prevalent digestive problems and complaints during pregnancy. Constipation occurs in 11%–40% of pregnancies and is more common in the first trimester. In addition, nausea and vomiting occur in 75% of pregnant women and averagely last for 35 days. In half of women, nausea resolves partially by the end of the 14th week but resolves fully in 22 weeks in 90% of those affected., This study aims at determining the relationship between digestive system diseases in pregnant women and stillbirth and neonatal death in Iran.
This population-based case-control study was conducted on 3573 mothers in 10 provinces of Iran, namely Fars, Yazd, Golestan, Hormozgan, Khorasan Razavi, Southern Khorasan, Hamadan, Kermanshah, Charmahal-O-Bakhtiari, and Kohgiloyue-Buyerahmad [Figure 1].
The case groups included 1223 mothers experiencing stillbirth and 1091 mothers with neonatal death. On the other hand, the control group included 1259 mothers with live births. These three groups were selected from primary health care (PHC) services in above-mentioned provinces from May 2014 to October 2015. Mothers with stillbirth were defined as those who had at least one stillbirth during the past 5 years (fetal death after 20 weeks of gestation). Mothers with neonatal death also referred to those who had at least one neonatal death during the past 5 years (neonate’s death within the first 28 days of life). Finally, mothers with live birth were defined as those who had not experienced any stillbirths, miscarriages, and neonatal deaths. First, baseline data extracted from medical records of mothers by health workers then these mothers invited to PHCs service offices for additional information. Objects of the study stated for mothers and those who agreed with participation included in the study.
Considering mother’s age, >35 years was a risk factor, the sample size was determined in each group. Accordingly, 3450 mothers (1150 mothers in each group) were enrolled in the study. Finally, 3580 mothers selected and enrolled into the study. After the required rectification and deletion of incomplete questionnaires, 3573 mothers were included in the study. Study participants were selected through cluster random sampling. In so doing, some health centers were randomly selected from the centers in each province, and some of the required information were gathered from the medical records of the women referring to these centers and some information was taken through interview. In each cluster, 10 questionnaires related to each case group (stillbirth and neonatal death) and 10 questionnaires related to the control group were completed. In cases that the 10 required questionnaires were not completed by stillbirth and neonatal death groups in each cluster, the nearest health center to the selected cluster was selected to compensate for the missing questionnaires. The study data were collected using a researcher-made questionnaire, including mother’s information such as mother’s height, weight, age, educational level, and smoking habit during pregnancy, and father’s age and educational level. The construct validity of the questionnaire was confirmed by experts. Furthermore the reliability was evaluated. In so doing, 50 questionnaires were filled by the control group and the Cronbach’s alpha was obtained as 0.64.
The questionnaires were completed by experienced or well-trained health workers. Some information was gathered through interviewing the mothers or using their medical records. Then, the data were entered into the Microsoft Excel software and analyzed using the SPSS software (IBM SPSS Statistics 21 software), version 19. Considering descriptive analysis, mean and standard deviation were used for quantitative variables and absolute and relative frequencies were used for nominal and ordinal ones. Besides, logistic regression analysis was employed to evaluate the relationship between the variables. The values of P < 0.05 were considered to be statistically significant.
Descriptive, demographic, and clinical information of the 3573 mothers and the results of univariate analysis are presented in [Table 1]. According to the results of univariate analysis [Table 1], the odds of stillbirth was 29% higher in the mothers suffering from digestive system diseases when compared to those without these disorders (odds ratio [OR]: 1.29, 95% confidence interval [CI] [1.01−1.63]). The odds of neonatal death was also 27% higher than in the mothers without digestive system diseases (OR: 1.27, 95% CI [1.02−1.64]). The relationships were statistically significant in both study groups. Moreover, the odds of stillbirth and neonatal death were, respectively, 38% and 54% higher in obese women (body mass index [BMI] > 30) than in those with normal weight (19 < BMI <25) (OR: 1.38, 95% CI [1.01−1.95]; OR: 1.54, 95% CI [1.09−2.19]).
The results of multivariate analysis of the factors related to stillbirth and neonatal death in the mothers suffering from digestive system diseases are presented in [Table 2]. Accordingly, the odds of stillbirth was 0.32 times higher in the mothers with compared to those without digestive system diseases (OR: 1.32, 95% CI [1.008−1.74]). Moreover, the odds of stillbirth was 1.39 times higher in the illiterate women in comparison to those with academic degrees (OR: 2.39, 95% CI [1.38−4.12]).
The odds of neonatal death was also 0.58 times higher in the mothers suffering from digestive system diseases compared to those without such disorders (OR: 1.58, 95% CI [1.19−2.09]). Besides, the odds of neonatal death was 1.03 times greater in the mothers above 35 years old compared to those below the age of 35 years (OR: 2.03, 95% CI [1.34−3.07]).
This study was conducted on a large population of pregnant women in 10 different provinces of Iran. The main finding of this study was that in comparison to the healthy mothers, those affected by digestive system diseases were exposed to higher odds of severe prenatal consequences. In addition, the odds of stillbirth and neonatal death, as undesirable consequences, were, respectively, 0.32 and 0.58 times higher in the pregnant mothers affected by digestive system diseases than those without such problems. This indicated the undesirable effects of digestive system diseases on the fetus. The results of a study conducted in Finland revealed the occurrence of severe pregnancy outcomes in the women affected by intestine inflammation disease and ulcerative colitis in comparison to the reference group. In another investigation in California, the results of multivariate analysis based on different types of intestine inflammation disease revealed that intestine disease correlated with stillbirth and premature labor which finally led to neonatal death. It was also reported that such phenomena could result from using anti-inflammatory and steroidal medicines during pregnancy. Moreover, the findings of a study carried out in Washington showed that in comparison to the babies born from healthy mothers, those born from mothers with Crohn’s disease had a considerably higher chance of prematurity and death. Another study in Sweden also showed that the odds ratio (OR) of neonatal and fetal death in the past week of pregnancy was 1.28 in the mothers affected by intestine inflammation. In general, factors such as high concentration of prostaglandins, disorders in smooth muscles’ neurological control, and nutritional problems in the pregnant women affected by active digestive system diseases might cause premature labor and consequently, neonatal death., Nausea and vomiting resulting from pregnancy are among the digestive problems that are clearly different from their weak forms and are usually accompanied by nutritional problems, mother’s weight loss, and fluid and electrolyte imbalances. In such conditions, mothers often need special cares and treatments; otherwise, coma, convulsion, and fetal death might occur., Various studies have indicated that digestive system diseases are a risk factor for high-risk pregnancy. In other words, diagnostic measures intensified the severity of the disease and affected the pregnancy outcomes. Therefore, effective control of these diseases during pregnancy is of utmost importance. Unfortunately, physicians have no special instructions for treatment of digestive system diseases such as intestine inflammation, ulcerative colitis, and Crohn’s disease during pregnancy. The findings of this study demonstrated the relationship between the mothers’ education level and undesirable pregnancy outcomes. Accordingly, the odds of stillbirth and neonatal death were 1.39 times higher in the illiterate mothers than those with academic degrees. This is consistent with the results of a study conducted in Bangladesh. Similarly, the findings of another study in the U.S. revealed that the odds of stillbirth was 0.51 times higher in illiterate mothers and those with primary school degrees than those with academic degrees. Education level indicates the socioeconomic status, which is independently related to stillbirth. Hence, increasing the education level of mothers, as the primary caregivers of their neonates, can be a significant intervention for guaranteeing infants’ health. Our study results also demonstrated a significant direct relationship between the mothers’ age and occurrence of stillbirth and neonatal death. Accordingly, the OR of stillbirth and neonatal death were, respectively, 1.12 and 1 times higher in the pregnant mothers’ age above the age of 35 years than those below 35 years old. A retrospective cohort study in the U. S. also assessed stillbirth and neonatal mortality in pregnant women above and below 35 years of age. The results indicated that the odds of stillbirth increased in the mothers aging 35 years and above during 37–42 weeks of gestation. However, the odds of neonatal death decreased in these women, except at 42 weeks of gestation. In addition, the results of a study performed in Sweden showed that the odds of stillbirth was 2.2% in the mothers aging 35 years and above. Furthermore, the results of a study in Canada demonstrated an increase in neonatal death in the women age 35 years and above, which is consistent with findings of this study. Another important finding of our study was that the OR of stillbirth and neonatal death were, respectively, 1.034 and 0.59 times higher in the pregnant women with BMI >30 compared to those with normal BMI.,,,,,, A study in Missouri also revealed a significant difference between the pregnant women with BMI >30 and those with normal BMI regarding the incidence of stillbirth. In the same line, another study in Sweden showed that the odds of stillbirth was 2.5 in the pregnant women with BMI >30. In general, two factors, i.e., pregnancy and obesity, can lead to undesirable results such as preeclampsia, hypertension, macrosomia, difficult labor, and placenta previa in those above the age of 35 years. These conditions necessitate termination of pregnancy so that the mother’s life can be saved. Subsequently, the fetus will be lost.,,,, Furthermore, the probability of stillbirth increases in obese women due to the inappropriate function of the placenta.
In this study, the information was gathered through interviewing the mothers and referring to their medical records. Thus, retrospective design of the study, mothers’ forgetfulness, and deficiencies in recording the information could be mentioned as the study limitations. Many women affected by digestive system diseases have successful pregnancies. However, such women need early and appropriate treatments. According to the findings of this study, stillbirth and neonatal death mostly resulted from maternal factors most of which could be prevented. These results could serve as the basis for future interventional studies and evidence-based decision-making. Moreover, by implementation of perinatal services leveling in the health system, high-risk pregnancies regarding digestive system diseases can be quickly identified so as to provide mothers and children with the most effective services.
The authors would like to thank the Research Center for Health Sciences affiliated to Shiraz University of Medical Sciences and the Research Vice chancellors of Hormozgan University of Medical Sciences, Shiraz University of Medical Sciences, and other universities cooperating in this project. They are also grateful for Ms. A. Keivanshekouh at the Research Improvement Center of Shiraz University of Medical Sciences for editing final version of the manuscript.
Financial support and sponsorship
The project was approved and financially supported by vice chancellor of research in Shiraz and Hormozgan Universities of Medical Sciences with registration numbers (No. 93-01-42-8964) and (No. 94112) respectively.
Conflicts of interest
There are no conflicts of interest.
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2]