Association of Traumatic Injury With Adverse Pregnancy Outcomes in Taiwan, 2004 to 2014

Key Points Question Do differences exist in the risk of adverse pregnancy outcomes among women who had emergency treatment or hospitalization due to injuries compared with those who did not? Findings In this cohort study of 2 973 831 pregnant women, emergency treatment for injuries was associated with an increased risk of adverse pregnancy outcomes. Women with injury-related hospitalization were also at an increased risk of adverse pregnancy outcomes. Meaning This study found that pregnant women who sustained injuries requiring hospitalization or emergency department visits exhibited higher risks of adverse pregnancy outcomes, including premature delivery.


Introduction
Trauma is estimated to complicate 6% to 7% of all pregnancies and to be one of the leading nonobstetric causes of maternal death during pregnancy. [1][2][3] It is also associated with an increased risk of fetal death, with 3 to 7 fetal deaths per 100 000 live births. 4 Moreover, severe trauma is associated with a higher risk of fetal death. 5 Studies have suggested a direct association between trauma and maternal and fetal death during pregnancy. Motor vehicle collisions during pregnancy were indicated to be a significant risk factor for maternal and fetal deaths. 6 Pregnant women involved in burn incidents had a higher risk of death, with sepsis and smoke inhalation as the major risk factors. 7,8 Penetration trauma during pregnancy was also associated with increased fetal mortality and hospital stay. 2 Apart from fetal deaths, trauma has also been associated with other adverse pregnancy outcomes. Compared with control participants who did not experience trauma, women with trauma had increased odds of placental abruption, uterine rupture, and fetal distress. 9 Similarly, Schiff and Holt 10 indicated that women who were severely and nonseverely injured in motor vehicle collisions had higher risks of placental abruption and cesarean delivery. Weiss et al 11 reported that women with injury-related emergency department visits were more likely to experience placental abruption and cesarean delivery. In Taiwan, women with severe and minor injuries also had higher odds of preterm labor. 5 Relevant literature has suggested that trauma among pregnant women is associated with an increased risk of adverse outcomes in pregnancy and preterm labor. 5,[9][10][11] However, previous studies mostly have used only small data sets (nonnational data sets) and adjusted the final model with limited clinical variables. While exceptional studies, such as that by Cheng et al, 5 have used 1 national data set (ie, the National Health Insurance Research Database data set), our study investigated the association of trauma-related factors with adverse pregnancy outcomes by using 3 national data sets in Taiwan. Furthermore, we also included broad research variables. First, we estimated 3 categoric levels of hospitalization and emergency treatment: none, once, and more than once. Next, we adjusted the final model by using different types of comorbidities, such as anemia, heart disease, lung disease, diabetes, and kidney disease. Finally, we adjusted the model with different types of pregnancy treatments, such as amniocentesis, labor induction, and cervical cerclage surgery.

Data Sources
The current study used 3 national data sets-namely, the Taiwan

Definition of Variables
The main outcome variable was adverse pregnancy outcomes, and the most common adverse pregnancy outcome in Taiwan, premature delivery, was selected as the secondary outcome. We defined adverse pregnancy outcomes as 1 of the following: birth defects (ICD-9-CM codes 740-759), birth weight less than 2500 g (ICD-9-CM codes 765.01-765.08), premature delivery (ICD-9-CM codes 765.21-765.28), or stillbirth (ICD-9-CM code 779.9); a normal pregnancy outcome was defined as a full-term live birth with no birth defects and birth weight greater than 1500 g. Premature delivery was defined as delivery before the start of the 37th week of pregnancy; full-term delivery was defined as delivery at the 37th week of pregnancy or later.
For this study, basic demographic data were collected, including maternal age (<20, 20-34, or >34 years), race (Aboriginal and Non-Indigenous, given that Aboriginal populations were hypothesized to have a higher injury prevalence), and nationality (Taiwanese or other nationality).
Women younger than 20 years or older than 34 years have higher risks of complications during pregnancy. 14 We also collected data on pregnant women's income status (low, middle, and high income as well as nonself-income) and residential area (highly urbanized area, moderately urbanized area, new city, general city, and rural, agricultural, or aging city). Residential area was defined according to research by Cavazos-Rehg et al. 15 We also collected the following 3 clinical variables: other disease or substance use during pregnancy (yes or no), labor complications (yes or no), and specific medical treatment during pregnancy (yes or no). We defined pregnant women as having other diseases or engagement in substance use during pregnancy if they had at least 1 ICD-9 code for anemia, heart disease, lung disease, diabetes, infections (eg, syphilis), gestational diabetes, excessive or insufficient amniotic fluid, high blood pressure, pregnancy toxemia, incomplete cervix, history of giving birth to newborns weighing at least 4000 g, history of premature or underweight neonates, kidney disease, Rh factor allergy, autoimmune disease (eg, lupus erythematosus), prenatal bleeding, smoking during pregnancy, alcohol use disorder, or drug addiction during pregnancy. Drug addiction was defined as pregnant women who had at least 1 ICD-9 code related to substance use disorders (292.0-292.9, 304.00-304.93, 305.00-305.93, 648.30-648.34, 968.5, 969.9, 965.00-965.09, E854.1, E939.6, E850.0, E935.0, V654.2, or E938.5). We defined labor complications as any of the following medical conditions experienced during pregnancy: fever, fecal material in amniotic fluid, early water breakage, early placental detachment, placenta previa, massive bleeding, spasms during childbirth, acute labor, prolonged labor, abnormal labor progression, breech or fetal position, cephalopelvic disproportion, complications related to umbilical cord prolapse, anesthesia, or fetal distress. Specific medical treatment requirements during pregnancy were defined as 1 of the following: amniocentesis, villi examination, labor induction, birth induction, fetal placement, cervical cerclage surgery, or laparotomy.
Two clinical variables related to injury during pregnancy were used in the study: emergency medical treatment (yes or no) and hospitalization (yes or no). Data related to injury status were extracted from the National Health Insurance Research Database by using ICD-9-CM N codes 800 to 999. Women were defined as having received emergency medical treatment because of injury if they received an injury code diagnosis during treatment in the emergency department and as having required hospitalization owing to injury if they had records of hospitalization and injury diagnosis with ICD-9-CM codes.

Statistical Analysis
First, we described the distribution of adverse pregnancy outcomes and premature delivery with demographic, clinical, and injury-related variables by using absolute numbers and percentages. Next, we applied simple logistic regression to analyze the association between study outcomes (adverse pregnancy outcomes and premature delivery) and risk factors. We used P < .20 as a cutoff point to determine risk factors to be included in multivariable analysis, consistent with previous research. [16][17][18][19][20] We also chose the covariates in accordance with studies that confirmed the association between the covariates and outcome variables. For the multivariate analysis, we used multiple logistic regression with a backward selection to calculate the adjusted odds ratio (AOR) for each risk factor. We conducted 2 separate bivariate and multivariate analyses for adverse pregnancy outcomes and premature delivery. We assessed multicollinearity by using Cramer V and the χ 2 independence test.
This study used 95% CIs and an α value of .05. A 2-sided hypothesis test was used for all statistical analysis in this study, which was performed with Stata version 15 (StataCorp).         Abbreviation: OR, odds ratio. a Includes anemia, heart disease, lung disease, diabetes, infections (eg, syphilis), gestational diabetes, excessive or insufficient amniotic fluid, high blood pressure, pregnancy toxemia, incomplete cervix, a history of producing newborns weighing at least 4000 g, a history of producing premature newborns or underweight infants, kidney disease, Rh factor allergy, autoimmune disease (eg, lupus erythematosus), prenatal bleeding, smoking during pregnancy, alcoholism, and drug addiction during pregnancy.

JAMA Network Open | Obstetrics and Gynecology
b Includes fever, fecal material in amniotic fluid, early water breakage, early placental detachment, placenta previa, massive bleeding, spasms during childbirth, acute labor, prolonged labor, abnormal labor progression, breech or fetal position, cephalopelvic disproportion, complications related to umbilical cord prolapse, anesthesia, and fetal distress.
c Includes amniocentesis, villi examination, labor induction, birth induction, fetal placement, cervical cerclage surgery, and laparotomy.  Table 4 shows the results of the multiple logistic regression model for adverse pregnancy outcomes.

Multivariate Analysis Results of Risk Factors for Adverse Pregnancy Outcomes
In model 1, women who received emergency treatment for injuries were more likely to have adverse pregnancy outcomes (AOR, 1.08; 95% CI, 1.05-1.10) after controlling for other risk factors. Model 2 showed that women who received more than 1 emergency treatment because of injuries had a higher risk of adverse pregnancy outcomes (AOR, 1.35; 95% CI, 1.22-1.49) than did those who required none.
In model 3, after other risk factors were controlled for, women with injury-related hospitalization had a 53% higher probability of adverse pregnancy outcomes (AOR, 1.53; 95% CI, 1.41-1.65) than those without it.

Discussion
One of the key results in this study is that women who had emergency department visits or hospitalization due to injuries were more likely to have adverse pregnancy outcomes, including premature delivery, after controlling for demographic and clinical risk factors. This finding corroborates those of other studies indicating that women have higher risks of adverse pregnancy outcomes, such as premature delivery and preterm birth, if they are hospitalized or treated at an emergency department because of injury. 9,10,19 Such effects may be caused by increased risks of placental abruption, uterine rupture, and fetal distress due to injury. Studies have suggested that women who experience injury-related hospitalization have higher risks of placental abruption, uterine rupture, and fetal distress. 9,10 Research has also concluded that women who receive treatment at emergency departments due to injury have higher risks of placental abruption and uterine rupture. 19 These maternal conditions could increase risks of adverse outcomes, such as premature delivery, birth defects, low birth weight, and stillbirth. 21,22 Therefore, pregnant women sustaining minor or major injuries should be treated carefully by a multidisciplinary team that incorporates a trauma surgeon and an obstetrician.
In accordance with other studies, this study found that women who receive specific medical treatments, such as birth induction or labor induction, are more likely to have adverse pregnancy outcomes, including premature delivery. [23][24][25] This finding can be explained by the increased risk of adverse effects, such as hemorrhage and infection, from the induced termination of pregnancy.
Relevant literature has shown that the induced termination of pregnancy is also associated with an increased risk of hemorrhage and infection among pregnant women. 26 Our finding is consistent with those of studies indicating that women with labor complications, such as placenta previa, fetal distress, or massive bleeding, have increased probabilities of adverse pregnancy outcomes, including premature delivery. 21 [27][28][29] This result may be because of increased risks of placental abruption and placenta previa among women who smoke, drink alcohol, and experience prenatal bleeding. 21,22,30 Both placental abruption and placenta previa are common risk factors for adverse pregnancy outcomes. 21,22 In this study, advanced and young maternal age were associated with an increased risk of adverse pregnancy outcomes, including premature delivery, which is consistent with the results of other studies. 31-37 This finding may be because of prepregnancy obesity and an increased rate of fetal distress and preeclampsia associated with advanced maternal age, as suggested by other studies. [33][34][35] Other studies have supported our finding that an increased rate of complications during pregnancy may influence the risk of adverse pregnancy outcomes among young women. 36,37 Finally, our result is consistent with those of studies that have found that women with low incomes exhibit higher risks of adverse pregnancy outcomes 38-43 ; they may have access only to poor prenatal care and may have little access to health facilities. Research using data from the Indonesia Demographic and Health Survey concluded that the low household wealth index was associated with the underuse of prenatal care. 44 Furthermore, women with poor prenatal care had higher risks of adverse pregnancy outcomes. 45 Our main finding pertains to the association between injury and adverse pregnancy outcomes.
Both hospitalization and emergency visits owing to injury were associated with adverse pregnancy outcomes. The strengths of this study include the use of a nationwide data set with multiple sources of data constituting prospectively collected data and comprehensive clinical data.

Limitations
This study has several limitations. It was restricted to the variables for which data were available, including environment; prenatal care visit (including frequency and treatment given during visit), education level, and paternity; prehospital information; and injury mechanism. Although the 3 data sets we used encompass a wide range of variables, other variables, such as motor vehicle collision configuration, prehospital care, and prenatal care, which could play a crucial role in determining adverse pregnancy outcomes, are not readily available. This study used national-level data in Taiwan.
The results obtained can be generalized to countries with conditions similar to Taiwan's.
Nonetheless, caution should be exercised in generalizing them to other settings.

Conclusions
This study found that pregnant women who experience injury had higher risks of adverse pregnancy outcomes, including premature delivery. Both hospitalization and emergency department visits due to injury were associated with an increased risk of adverse pregnancy outcomes. Therefore, pregnant