- Email: [email protected]
Outcomes After Nonobstetric Surgery in Pregnant Patients
ORIGINAL ARTICLE
Outcomes After Nonobstetric Surgery in Pregnant Patients: A Nationwide Study Shih-Yu Huang, MD; Po-Han Lo, MD; Wei-Min Liu, MD; Yih-Giun Cherng, MD, MS; Chun-Chieh Yeh, MD, PhD; Ta-Liang Chen, MD, PhD; and Chien-Chang Liao, PhD, MPH Abstract Objective: To evaluate outcomes after nonobstetric surgical procedures in pregnant patients. Methods: We conducted a retrospective cohort study of 5591 pregnant women who underwent nonobstetric surgical procedures using Taiwan’s National Health Insurance Research Database 2008-2012 claims data. Using a propensity score matching procedure, 22,364 nonpregnant women were selected for comparison. Logistic regression was used to calculate the odds ratios (ORs) and 95% CIs of postoperative complications and in-hospital mortality associated with pregnancy. Results: Pregnant women had higher risks of postoperative septicemia (OR¼1.75; 95% CI, 1.47-2.07), pneumonia (OR¼1.47; 95% CI, 1.01-2.13), urinary tract infection (OR¼1.29; 95% CI, 1.08-1.54), and in-hospital mortality (OR¼3.94; 95% CI, 2.62-5.92) compared with nonpregnant women. Pregnant women also had longer hospital stays and higher medical expenditures after nonobstetric surgical procedures than controls. Higher rates of postoperative adverse events in pregnant women receiving nonobstetric surgery were noted in all age groups. Conclusion: Surgical patients with pregnancy showed more adverse events, with a risk of in-hospital mortality approximately 4-fold higher after nonobstetric surgery compared with nonpregnant patients. These findings suggest the urgent need to revise the protocols for postoperative care for this population. ª 2016 Mayo Foundation for Medical Education and Research
For editorial comment, see page 1151; for related article, see page 1158 From the Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan (S.-Y.H., P.-H.L., Y.G.C.); Department of Anesthesiology, School of Medicine, Taipei Medical University, Taipei, Taiwan (S.Y.H., P.-H.L., Y.-G.C., T.-L.C., C.-C.L.); Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei, Taiwan (W.M.L.); Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan Affiliations continued at the end of this article.
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regnancy is marked by major cardiovascular, respiratory, gastrointestinal, hematologic, endocrine, nervous, and renal system changes that affect preexisting medical conditions and make clinical assessments more complex and challenging.1 Although pregnancy complicates disease status, whether pregnancy itself has protective or harmful effects is not well understood. Some studies have found protective effects of pregnancy, such as a decreased incidence of acute appendicitis and an improved critical illness condition prognosis.2,3 Other studies have suggested that pregnant status is associated with worse breast cancer or traumatic brain injury outcomes.4,5 Pregnant women also experience diseases that require surgical interventions, with an estimated 2% needing nonobstetric surgical procedures during the antepartum period. Mortality from such surgical procedures has been estimated to be 0.006% to 0.25%.6,7 Several recent studies have investigated perioperative outcomes after
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nonobstetric surgical procedures in pregnant women, but the association between pregnancy and postoperative outcomes remains controversial.6-17 Some studies suggested that pregnancy is associated with higher rates of perioperative maternal complications,8,9 and other studies reported no significant differences in postoperative complications and mortality rates between pregnant and nonpregnant women.10-12 However, these previous investigations were limited by several factors, such as focusing on specific types of surgery,8-14 analysis based on smaller samples of pregnant women,11,13-17 studies conducted without matching procedure,6,7,13-16 or inadequate adjustment for potential confounding factors.8-11 Using claims data from Taiwan’s National Health Insurance Research Database, we conducted a nationwide cohort study to compare major complications and in-hospital mortality rates after nonobstetric surgical procedures in pregnant and nonpregnant women.
Mayo Clin Proc. n September 2016;91(9):1166-1172 n http://dx.doi.org/10.1016/j.mayocp.2016.06.021 www.mayoclinicproceedings.org n ª 2016 Mayo Foundation for Medical Education and Research
OUTCOMES IN PREGNANT SURGICAL PATIENTS
METHODS Source of Data Taiwan’s National Health Insurance program was implemented in March 1995 and covers more than 99% of Taiwan’s 23 million residents. This study used reimbursement claims data from Taiwan’s National Health Insurance Research Database. The National Health Research Institutes established this database to record all beneficiaries’ medical services, including inpatient and outpatient demographic characteristics, physicians’ primary and secondary diagnoses, treatment procedures, prescriptions, and medical expenditures. Research articles based on data from this database have been accepted in prominent scientific journals worldwide.18-22 Ethical Approval To protect personal privacy, the electronic database was decoded, with patient identifications scrambled for further public access for research. According to National Health Research Institutes regulations, informed consent is not required because of the use of decoded and scrambled patient identifications. However, this study was evaluated and approved by Taiwan’s National Health Research Institutes and the institutional review board of Taipei Medical University (TMU-JIRB-201505055; TMU-JIRB201404070). This study was conducted in accordance with the Helsinki Declaration. Study Design We examined medical claims and identified 5591 pregnant patients 18 years and older from 591,445 patients who underwent major inpatient nonobstetric surgical procedures from January 1, 2008, through December 31, 2012. These procedures required general, epidural, or spinal anesthesia and hospitalization for more than 1 day. Each pregnant surgical patient was matched with 4 randomly selected nonpregnant female surgical patients. We conducted the analysis using a propensity score matched pair procedure and considered age, low income, whether the operation took place in a medical center, coexisting medical conditions, types of nonobstetric surgery, and types of anesthesia. Measures and Definitions We identified patient income status by defining low income as qualifying for waived medical Mayo Clin Proc. n September 2016;91(9):1166-1172 www.mayoclinicproceedings.org
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copayment because this status is verified by the insurance bureau. Also recorded were whether the surgery was performed in a medical center and the types of nonobstetric surgery and anesthesia. Taiwan defines medical centers as hospitals that (1) provide research, teaching, and high-quality medical care; (2) have at least 500 acute inpatient care beds; and (3) have departments of family medicine, internal medicine, surgical medicine, obstetrics and gynecology, pediatrics, orthopedics, neurosurgery, plastic surgery, urology, otolaryngology, ophthalmology, dermatology, neurology, psychiatry, rehabilitation, anesthesiology, radiology, pathology, nuclear medicine, dentistry, emergency medicine, and occupational medicine. The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) was used to define physicians’ diagnoses in the National Health Insurance system. Based on previous surgical studies,18-22 preexisting medical conditions that were determined from medical claims for the 24-month preoperative period included mental disorders (ICD-9-CM codes 290-319), chronic obstructive pulmonary disease (ICD-9CM codes 490-496), hypertension (ICD-9-CM codes 401-405), diabetes (ICD-9-CM code 250), hyperlipidemia (ICD-9-CM codes 272.0, 272.1, and 272.2), ischemic heart disease (ICD-9-CM codes 410-414), epilepsy (ICD-9CM code 345), liver cirrhosis (ICD-9-CM code 571), and congestive heart failure (ICD-9-CM code 428). Renal dialysis was defined by administration codes (D8 and D9). In-hospital mortality after the index surgery was considered the study’s primary outcome. Nine major postoperative complications were considered secondary outcomes: septicemia (ICD-9-CM codes 038 and 998.5), pneumonia (ICD-9-CM codes 480-486), stroke (ICD-9-CM codes 430-438), urinary tract infection (ICD-9-CM code 599.0), acute renal failure (ICD-9-CM code 584), deep wound infection (ICD-9-CM code 958.3), pulmonary embolism (ICD-9-CM code 415), postoperative bleeding (ICD-9-CM codes 998.0, 998.1, and 998.2), and acute myocardial infarction (ICD-9-CM code 410).18-22 Admission to the intensive care unit, length of hospital stay, and medical expenditures after the index surgery were also compared. Postoperative adverse events noted included septicemia, pneumonia, urinary tract infection, and in-hospital mortality.
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TABLE 1. Characteristics of Pregnant and Nonpregnant Surgical Patientsa Patients (No. [%]) Nonpregnant (N¼22,364)
Characteristic Age (y) 18-24 25-29 30-34 35-39 40-44 45-50 Low income Operation in a medical center Types of nonobstetric surgery Digestive Musculoskeletal Kidney, ureter, bladder Respiratory Neurosurgery Breast Cardiovascular Skin Eye Others Types of anesthesia General Epidural or spinal Coexisting medical conditions Mental disorders Chronic obstructive pulmonary disease Hypertension Diabetes Hyperlipidemia Ischemic heart disease Epilepsy Liver cirrhosis Renal dialysis Congestive heart failure a
Pregnant (N¼5591)
3900 6688 7160 3276 872 468 568 8684
(17.4) (29.9) (32.0) (14.7) (3.9) (2.1) (2.5) (38.8)
975 1672 1790 819 218 117 142 2171
(17.4) (29.9) (32.0) (14.6) (3.9) (2.1) (2.5) (38.8)
9992 5324 1120 1120 904 852 696 500 172 1684
(44.7) (23.8) (5.0) (5.0) (4.0) (3.8) (3.1) (2.2) (0.8) (7.5)
2498 1331 280 280 226 213 174 125 43 421
(44.7) (23.8) (5.0) (5.0) (4.0) (3.8) (3.1) (2.2) (0.8) (7.5)
16,024 (71.7) 6340 (28.3) 2144 680 288 252 124 72 48 44 20 8
4006 (71.7) 1585 (28.3)
(9.6) (3.0) (1.3) (1.1) (0.6) (0.3) (0.2) (0.2) (0.1) (0.04)
536 170 72 63 31 18 12 11 5 2
(9.6) (3.0) (1.3) (1.1) (0.6) (0.3) (0.2) (0.2) (0.1) (0.04)
P>.99 for all characteristics.
Statistical Analyses Propensity score matched pairs analyses were used to determine associations between pregnancy and the primary outcome (in-hospital mortality after surgery). We developed a nonparsimonious multivariable logistic regression model to estimate a propensity score for pregnant surgical patients. Clinical significance guided the initial choice of covariates in this model: age, low income, medical center, types of nonobstetric surgery and anesthesia, mental disorders, chronic obstructive pulmonary disease, hypertension, diabetes, hyperlipidemia, ischemic heart disease, epilepsy, liver 1168
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cirrhosis, congestive heart failure, and renal dialysis. We matched pregnant women to nonpregnant women using a greedy matching algorithm (without replacement) with a caliper width of 0.2 SD of the log odds of the estimated propensity score. This method could remove 98% of the bias from measured covariates.23,24 Categorical variables are summarized using frequency (percentage) and were compared between pregnant and nonpregnant surgical patients using a c2 test. Continuous variables are summarized using mean SD and were compared using a t test. Logistic regression was used to calculate the odds ratios (ORs) and 95% CIs of postoperative complications and in-hospital mortality associated with pregnancy. Additional analyses stratified by age, number of medical conditions, and types of surgery were also performed to examine adverse events in pregnant women within these strata. RESULTS Table 1 shows the baseline characteristics of pregnant patients and controls who underwent nonobstetric surgery. After propensity score matching, there were no significant differences in groups of surgical patients with and without pregnancy analyzed by age, low income, whether the operation occurred in a medical center, types of nonobstetric surgery and anesthesia, mental disorders, chronic obstructive pulmonary disease, hypertension, diabetes, hyperlipidemia, ischemic heart disease, epilepsy, liver cirrhosis, renal dialysis, or congestive heart failure. Compared with nonpregnant patients, pregnant patients had higher risks of postoperative septicemia (OR¼1.75; 95% CI, 1.47-2.07), pneumonia (OR¼1.47; 95% CI, 1.01-2.13), urinary tract infection (OR¼1.29; 95% CI, 1.081.54), and in-hospital mortality (OR¼3.94; 95% CI, 2.62-5.92) (Table 2). Pregnancy was also associated with adverse events (OR¼1.63; 95% CI, 1.45-1.84) and admission to the intensive care unit (OR¼2.46; 95% CI, 2.22-2.73) after surgery. Mean SD medical expenditures ($3435$4943 vs $1891$3017; P<.001) and hospital length of stay (10.916.2 vs 5.89.5 days; P<.001) were comparatively greater for pregnant patients. In the stratification analysis, associations between pregnancy and postoperative adverse events were significant in women aged 18 to
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24 years (OR¼1.83; 95% CI, 1.37-2.44), 25 to 29 years (OR¼1.73; 95% CI, 1.40-2.14), 30 to 34 years (OR¼1.63; 95% CI, 1.32-2.01), and 35 years and older (OR¼1.40; 95% CI, 1.09-1.80) (Table 3). Pregnancy was also associated with postoperative adverse events in women who had no medical conditions (OR¼1.70; 95% CI, 1.50-1.93). Pregnant women who underwent cardiovascular surgery had the highest postoperative adverse event risk compared with nonpregnant women (OR¼2.98; 95% CI, 2.01-4.41). DISCUSSION In this nationwide retrospective cohort study, we analyzed reimbursement claims from Taiwan’s National Health Insurance Research Database and found increased risks of postoperative bleeding, septicemia, pneumonia, urinary tract infection, and in-hospital mortality after nonobstetric surgical procedures in pregnant women. The association between pregnancy and postoperative adverse events was most significant in women undergoing cardiovascular surgical procedures. This study had several strengths in addition to its large sample size and cohort study design. Various types of surgical procedures were analyzed, and a propensity score matching study design and multivariate adjustment also were used. Based on data from previous investigations,25-28 age, socioeconomic status, and level of hospital were associated with postoperative outcomes and thus should be considered as potential confounding factors when investigating associations between pregnancy and postoperative outcomes. In addition, previous studies identified coexisting medical conditions as independent determinants in perioperative complications and mortality, including hypertension,29 diabetes,18 mental disorders,19 congestive heart failure,30 chronic obstructive pulmonary disease,29 ischemic heart disease,29 hyperlipidemia,31 epilepsy,20 liver cirrhosis,21,31 and renal dialysis.22,29 To most accurately investigate postoperative outcomes in pregnant patients, we adjusted for sociodemographic features and coexisting medical conditions in the multivariate regression models. After adjustment for potential confounding factors, the present study found that pregnancy is an independent factor associated with postoperative Mayo Clin Proc. n September 2016;91(9):1166-1172 www.mayoclinicproceedings.org
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TABLE 2. Adverse Events After Nonobstetric Surgery in Pregnant and Nonpregnant Patientsa Adverse event Postoperative complications (%) Septicemia Pneumonia Urinary tract infection Stroke Deep wound infection Acute renal failure Acute myocardial infarction Postoperative bleeding Pulmonary embolism In-hospital mortality (%) ICU stay (%) Adverse events (%)c Medical expenditures ($), mean SD Length of hospital stay (d), mean SD
Nonpregnant patients
Pregnant patients
2.05 0.47 2.34 0.32 0.50 0.21 0.01 0.53 0.05 0.21 5.02 4.74 18913017
3.52 0.68 3.00 0.39 0.47 0.18 0.00 0.63 0.02 0.82 11.52 7.51 34354943
5.89.5
10.916.2
OR (95% CI)b 1.75 1.47 1.29 1.22 0.93 0.85
(1.47-2.07) (1.01-2.13) (1.08-1.54) (0.76-1.97) (0.61-1.42) (0.43-1.69) – 1.19 (0.81-1.73) 0.36 (0.05-2.82) 3.94 (2.62-5.92) 2.46 (2.22-2.73) 1.63 (1.45-1.84) P<.001 P<.001
ICU ¼ intensive care unit; OR ¼ odds ratio. Adjusted for age, low income, operation in a medical center, types of anesthesia and surgery, and coexisting medical conditions. c Adverse events include septicemia, pneumonia, urinary tract infection, and in-hospital mortality. a
b
in-hospital mortality, pneumonia, and septicemia after nonobstetric surgical procedures. We found effect of pregnancy on postoperative adverse events to be significant but varying by age group. Pregnant women 35 years and older still have increased odds of adverse events compared with nonpregnant women, but the odds of adverse events in this age group is lower than that of the 18- to 24-year old group. Previous studies investigated the effects of pregnancy in various clinical situations.2,4,32-34 Two studies found that pregnant women are less likely to be diagnosed as having acute appendicitis than are nonpregnant women.2,32 However, one large-scale investigation revealed that pregnancy may be a risk factor for increased severity of Crohn disease.35 Regarding the effect of pregnancy on the course and severity of breast cancer, various studies have claimed equivalent prognosis, protective effect, and harmful effect.4,33,34 The influence of pregnancy on maternal surgical outcome is still inconclusive.6-17 One study focusing on maternal surgical outcome after appendectomy and cholecystectomy found that pregnancy does not increase postoperative morbidity.12 A second population-based study also stated that
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TABLE 3. Risk of Postoperative Adverse Events in Pregnant and Nonpregnant Patients in a Stratification Analysis by Age, Medical Conditions, and Types of Surgerya Adverse events (No. [%])b
OR (95% CI)c
3900 975
163 (4.18) 72 (7.38)
1.00 (Reference) 1.83 (1.37-2.44)
6688 1672
308 (4.61) 129 (7.72)
1.00 (Reference) 1.73 (1.40-2.14)
7160 1790
326 (4.55) 129 (7.21)
1.00 (Reference) 1.63 (1.32-2.01)
4616 1154
263 (5.70) 90 (7.80)
1.00 (Reference) 1.40 (1.09-1.80)
18,960 4740
885 (4.67) 364 (7.68)
1.00 (Reference) 1.70 (1.50-1.93)
3404 851
175 (5.14) 56 (6.58)
1.00 (Reference) 1.30 (0.95-1.77)
7003 2030
460 (6.57) 182 (8.97)
1.00 (Reference) 1.40 (1.17-1.68)
5324 1329
123 (2.31) 55 (4.14)
1.00 (Reference) 1.83 (1.32-2.52)
Patients (No.) Age 18-24 y Not pregnant Pregnant Age 25-29 y Not pregnant Pregnant Age 30-34 y Not pregnant Pregnant Age 35 y Not pregnant Pregnant No medical conditions Not pregnant Pregnant 1 Medical conditions Not pregnant Pregnant Abdominal surgery Not pregnant Pregnant Musculoskeletal surgery Not pregnant Pregnant Cardiovascular surgery Not pregnant Pregnant Neurosurgery Not pregnant Pregnant Digestive surgery Not pregnant Pregnant
664 171
89 (13.40) 54 (31.58)
1.00 (Reference) 2.98 (2.01-4.4 1)
904 226
46 (5.09) 18 (7.96)
1.00 (Reference) 1.61 (0.92-2.84)
9992 2498
497 (4.97) 196 (7.85)
1.00 (Reference) 1.63 (1.37-1.93)
OR ¼ odds ratio. Adverse events include postoperative septicemia, pneumonia, urinary tract infection, and inhospital mortality. c Adjusted for age, low income, operation in a medical center, types of anesthesia and surgery, and coexisting medical conditions. a
b
pregnancy was not a significant predictor for having a surgical complication after cholecystectomy.10 Another study investigated complications after breast cancer surgery and also found similar outcomes between women with and without pregnancy.11 Nevertheless, in a study regarding thyroid and parathyroid surgery, pregnant women have worse clinical and economic outcomes than nonpregnant women.9 Although these studies provided some information, focusing only on specific types of surgery was their main limitation. Unlike these previous 1170
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investigations,6-17 the present study’s strengths were its large sample size, cohort study design, multivariate adjustment, and comparison of various types of surgery. Some possible explanations may clarify why pregnant women had increased postoperative complications and in-hospital mortality after nonobstetric surgical procedures. First, anatomic and physiologic changes during pregnancy may increase the complexity and difficulty of disease diagnosis and management.1,13 The possibility of delayed diagnosis or inappropriate management of surgical disease may consequently contribute to worse outcomes. Second, the “wait and see” strategy is commonly used in pregnant women to postpone invasive procedures to later in pregnancy or to the postpartum period.36 The policy of deferring surgical intervention may allow the surgical disease to progress. Another explanation is that pregnancy per se may influence the severity of some surgical disease,12,37,38 which may become more severe compared with the same condition in nonpregnant women when surgery is ultimately performed. More advanced surgical disease may result in worse postoperative outcomes. Third, pregnancy per se is a factor in increasing susceptibility to or severity of infectious diseases, including viral, bacterial, and parasitic infections; this is why we investigated increased postoperative septicemia in pregnant women.39 Finally, pregnant patients undergoing surgery may receive more attention and monitoring in the postoperative period, and, therefore, there is an increased possibility of longer hospitalization, admission to the intensive care unit, and higher medical expenditures. This study has some limitations. First, detailed socioeconomic and lifestyle information and data on severity of comorbid disease and biochemical measures were not available from Taiwan’s National Health Insurance Research Database. Second, information about pathology and details about the presentation or severity of the surgical disease could not be obtained. Therefore, the influence of surgical disease severity on maternal surgical outcome could not be optimally adjusted for. Third, because the database lacks records regarding gestational age and trimester of pregnancy, we could not investigate differences in postoperative outcome among the trimesters and validate the impact of surgical
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intervention in various trimesters. In addition, the coexisting medical conditions included in this study were based on previous surgical studies’ suggestions.18-22 That other coexisting diseases were not considered is one of the present study’s limitations. Finally, the definition of postoperative adverse events in this study included only pneumonia, septicemia, uninary tract infection, and in-hospital mortality; that it did not include all complications may be considered a study limitation. CONCLUSION This nationwide cohort study associated pregnancy with higher in-hospital mortality and risk of pneumonia, septicemia, and postoperative bleeding after nonobstetric surgery. These data suggest a need to provide better perioperative management and monitoring in this population to prevent or minimize postoperative complications. ACKNOWLEDGMENTS This study is based in part on data obtained from the National Health Insurance Research Database. This database is provided by the Bureau of National Health Insurance of Taiwan’s Ministry of Health and Welfare and is managed by the National Health Research Institutes. The authors’ interpretations and conclusions do not represent those of the Bureau of National Health Insurance, the Ministry of Health and Welfare, or the National Health Research Institutes. Prof. Ta-Liang Chen has equal contribution with the corresponding author. Abbreviations and Acronyms: ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification; ICU = intensive car unit; OR = odds ratio Affiliations (Continued from the first page of this article.): (W.-M.L.); Department of Surgery, China Medical University Hospital, Taichung, Taiwan (C.-C.Y.); Department of Surgery, University of Illinois, Chicago, IL, USA (C.-C.Y.); Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan (T.-L.C., C.-C.L.); Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan (T.-L.C., C.-C.L.); School of Chinese Medicine, China Medical University, Taichung, Taiwan (C.-C.L.) Grant Support: This study was supported in part by grants from Shuang Ho Hospital, Taipei Medical University (104TMU-SHH-23), Taiwan’s Ministry of Science and Technology (MOST104-2314-B-038-027-MY2; NSC1022314-B-038-021-MY3), and Taiwan’s Ministry of Health Mayo Clin Proc. n September 2016;91(9):1166-1172 www.mayoclinicproceedings.org
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and Welfare Clinical Trial and Research Center of Excellence (MOHW105-TDU-B-212-133019). Correspondence: Address to Chien-Chang Liao, PhD, MPH, or Ta-Liang Chen, MD, PhD, Department of Anesthesiology, Taipei Medical University Hospital, 252 Wuxing St, Taipei 110, Taiwan ([email protected]; [email protected]).
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21. Lin CS, Lin SY, Chang CC, et al. Postoperative adverse outcomes after non-hepatic surgery in patients with liver cirrhosis. Br J Surg. 2013;100(13):1784-1790. 22. Cherng YG, Liao CC, Chen TH, et al. Are non-cardiac surgeries safe for dialysis patients? a population-based retrospective cohort study. PLoS One. 2013;8(3):e58942. 23. Rosenbaum PR, Rubin DB. Constructing a control group using multivariate matched sampling methods that incorporate the propensity score. Am Stat. 1985;39:33-38. 24. Wijeysundera DN, Beattie WS, Austin PC, Hux JE, Laupacis A. Epidural anaesthesia and survival after intermediate-to-high-risk non-cardiac surgery: a population-based cohort study. Lancet. 2008;372(9638):562-569. 25. Jin F, Chung F. Minimizing perioperative adverse events in the elderly. Br J Anaesth. 2001;87(4):608-624. 26. Vogel TR, Dombrovskiy VY, Carson JL, et al. Postoperative sepsis in the United States. Ann Surg. 2010;252(6):10651071. 27. Vartak S, Ward MM, Vaughn TE. Do postoperative complications vary by hospital teaching status? Med Care. 2008;46(1):25-32. 28. Bagger JP, Zindrou D, Taylor KM. Postoperative infection with meticillin-resistant Staphylococcus aureus and socioeconomic background. Lancet. 2004;363(9410):706-708. 29. Kristensen SD, Knuuti J, Saraste A, et al. 2014 ESC/ESA guidelines on non-cardiac surgery: cardiovascular assessment and management. Eur Heart J. 2014;35(35):2383-2431. 30. Hernandez AF, Whellan DJ, Stroud S, et al. Outcomes in heart failure patients after major noncardiac surgery. J Am Coll Cardiol. 2004;44(7):1446-1453.
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31. Maia PC, Abelha FJ. Predictors of major postoperative cardiac complications in a surgical ICU. Rev Port Cardiol. 2008;27(3): 321-328. 32. Zingone F, Sultan AA, Humes DJ, et al. Risk of acute appendicitis in and around pregnancy: a population-based cohort study from England. Ann Surg. 2015;261(2):332-337. 33. Azim HA Jr, Santoro L, Pavlidis N, et al. Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies. Eur J Cancer. 2011;47(1):74-83. 34. Cardonick E, Dougherty R, Grana G, et al. Breast cancer during pregnancy: maternal and fetal outcomes. Cancer J. 2010;16(1): 76-82. 35. Hatch Q, Champagne BJ, Maykel JA, et al. The impact of pregnancy on surgical Crohn disease: an analysis of the Nationwide Inpatient Sample. J Surg Res. 2014;190(1):41-46. 36. Nguyen GC, Dinani AM, Pivovarov K. Endoscopic management and outcomes of pregnant women hospitalized for nonvariceal upper GI bleeding: a nationwide analysis. Gastrointest Endosc. 2010;72(5):954-959. 37. Van Mook WN, Peeters L. Severe cardiac disease in pregnancy, part I: hemodynamic changes and complaints during pregnancy, and general management of cardiac disease in pregnancy. Curr Opin Crit Care. 2005;11(5):430-434. 38. Aydin Y, Can SM, Gulkilik A, et al. Rapid enlargement and recurrence of a preexisting intrasellar craniopharyngioma during the course of two pregnancies: case report. J Neurosurg. 1999; 91(2):322-324. 39. Kourtis AP, Read JS, Jamieson DJ. Pregnancy and infection. N Engl J Med. 2014;370(23):2211-2218.
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Outcomes After Nonobstetric Surgery in Pregnant Patients: A Nationwide Study Shih-Yu Huang, MD; Po-Han Lo, MD; Wei-Min Liu, MD; Yih-Giun Cherng, MD, MS; Chun-Chieh Yeh, MD, PhD; Ta-Liang Chen, MD, PhD; and Chien-Chang Liao, PhD, MPH Abstract Objective: To evaluate outcomes after nonobstetric surgical procedures in pregnant patients. Methods: We conducted a retrospective cohort study of 5591 pregnant women who underwent nonobstetric surgical procedures using Taiwan’s National Health Insurance Research Database 2008-2012 claims data. Using a propensity score matching procedure, 22,364 nonpregnant women were selected for comparison. Logistic regression was used to calculate the odds ratios (ORs) and 95% CIs of postoperative complications and in-hospital mortality associated with pregnancy. Results: Pregnant women had higher risks of postoperative septicemia (OR¼1.75; 95% CI, 1.47-2.07), pneumonia (OR¼1.47; 95% CI, 1.01-2.13), urinary tract infection (OR¼1.29; 95% CI, 1.08-1.54), and in-hospital mortality (OR¼3.94; 95% CI, 2.62-5.92) compared with nonpregnant women. Pregnant women also had longer hospital stays and higher medical expenditures after nonobstetric surgical procedures than controls. Higher rates of postoperative adverse events in pregnant women receiving nonobstetric surgery were noted in all age groups. Conclusion: Surgical patients with pregnancy showed more adverse events, with a risk of in-hospital mortality approximately 4-fold higher after nonobstetric surgery compared with nonpregnant patients. These findings suggest the urgent need to revise the protocols for postoperative care for this population. ª 2016 Mayo Foundation for Medical Education and Research
For editorial comment, see page 1151; for related article, see page 1158 From the Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan (S.-Y.H., P.-H.L., Y.G.C.); Department of Anesthesiology, School of Medicine, Taipei Medical University, Taipei, Taiwan (S.Y.H., P.-H.L., Y.-G.C., T.-L.C., C.-C.L.); Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei, Taiwan (W.M.L.); Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan Affiliations continued at the end of this article.
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regnancy is marked by major cardiovascular, respiratory, gastrointestinal, hematologic, endocrine, nervous, and renal system changes that affect preexisting medical conditions and make clinical assessments more complex and challenging.1 Although pregnancy complicates disease status, whether pregnancy itself has protective or harmful effects is not well understood. Some studies have found protective effects of pregnancy, such as a decreased incidence of acute appendicitis and an improved critical illness condition prognosis.2,3 Other studies have suggested that pregnant status is associated with worse breast cancer or traumatic brain injury outcomes.4,5 Pregnant women also experience diseases that require surgical interventions, with an estimated 2% needing nonobstetric surgical procedures during the antepartum period. Mortality from such surgical procedures has been estimated to be 0.006% to 0.25%.6,7 Several recent studies have investigated perioperative outcomes after
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nonobstetric surgical procedures in pregnant women, but the association between pregnancy and postoperative outcomes remains controversial.6-17 Some studies suggested that pregnancy is associated with higher rates of perioperative maternal complications,8,9 and other studies reported no significant differences in postoperative complications and mortality rates between pregnant and nonpregnant women.10-12 However, these previous investigations were limited by several factors, such as focusing on specific types of surgery,8-14 analysis based on smaller samples of pregnant women,11,13-17 studies conducted without matching procedure,6,7,13-16 or inadequate adjustment for potential confounding factors.8-11 Using claims data from Taiwan’s National Health Insurance Research Database, we conducted a nationwide cohort study to compare major complications and in-hospital mortality rates after nonobstetric surgical procedures in pregnant and nonpregnant women.
Mayo Clin Proc. n September 2016;91(9):1166-1172 n http://dx.doi.org/10.1016/j.mayocp.2016.06.021 www.mayoclinicproceedings.org n ª 2016 Mayo Foundation for Medical Education and Research
OUTCOMES IN PREGNANT SURGICAL PATIENTS
METHODS Source of Data Taiwan’s National Health Insurance program was implemented in March 1995 and covers more than 99% of Taiwan’s 23 million residents. This study used reimbursement claims data from Taiwan’s National Health Insurance Research Database. The National Health Research Institutes established this database to record all beneficiaries’ medical services, including inpatient and outpatient demographic characteristics, physicians’ primary and secondary diagnoses, treatment procedures, prescriptions, and medical expenditures. Research articles based on data from this database have been accepted in prominent scientific journals worldwide.18-22 Ethical Approval To protect personal privacy, the electronic database was decoded, with patient identifications scrambled for further public access for research. According to National Health Research Institutes regulations, informed consent is not required because of the use of decoded and scrambled patient identifications. However, this study was evaluated and approved by Taiwan’s National Health Research Institutes and the institutional review board of Taipei Medical University (TMU-JIRB-201505055; TMU-JIRB201404070). This study was conducted in accordance with the Helsinki Declaration. Study Design We examined medical claims and identified 5591 pregnant patients 18 years and older from 591,445 patients who underwent major inpatient nonobstetric surgical procedures from January 1, 2008, through December 31, 2012. These procedures required general, epidural, or spinal anesthesia and hospitalization for more than 1 day. Each pregnant surgical patient was matched with 4 randomly selected nonpregnant female surgical patients. We conducted the analysis using a propensity score matched pair procedure and considered age, low income, whether the operation took place in a medical center, coexisting medical conditions, types of nonobstetric surgery, and types of anesthesia. Measures and Definitions We identified patient income status by defining low income as qualifying for waived medical Mayo Clin Proc. n September 2016;91(9):1166-1172 www.mayoclinicproceedings.org
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copayment because this status is verified by the insurance bureau. Also recorded were whether the surgery was performed in a medical center and the types of nonobstetric surgery and anesthesia. Taiwan defines medical centers as hospitals that (1) provide research, teaching, and high-quality medical care; (2) have at least 500 acute inpatient care beds; and (3) have departments of family medicine, internal medicine, surgical medicine, obstetrics and gynecology, pediatrics, orthopedics, neurosurgery, plastic surgery, urology, otolaryngology, ophthalmology, dermatology, neurology, psychiatry, rehabilitation, anesthesiology, radiology, pathology, nuclear medicine, dentistry, emergency medicine, and occupational medicine. The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) was used to define physicians’ diagnoses in the National Health Insurance system. Based on previous surgical studies,18-22 preexisting medical conditions that were determined from medical claims for the 24-month preoperative period included mental disorders (ICD-9-CM codes 290-319), chronic obstructive pulmonary disease (ICD-9CM codes 490-496), hypertension (ICD-9-CM codes 401-405), diabetes (ICD-9-CM code 250), hyperlipidemia (ICD-9-CM codes 272.0, 272.1, and 272.2), ischemic heart disease (ICD-9-CM codes 410-414), epilepsy (ICD-9CM code 345), liver cirrhosis (ICD-9-CM code 571), and congestive heart failure (ICD-9-CM code 428). Renal dialysis was defined by administration codes (D8 and D9). In-hospital mortality after the index surgery was considered the study’s primary outcome. Nine major postoperative complications were considered secondary outcomes: septicemia (ICD-9-CM codes 038 and 998.5), pneumonia (ICD-9-CM codes 480-486), stroke (ICD-9-CM codes 430-438), urinary tract infection (ICD-9-CM code 599.0), acute renal failure (ICD-9-CM code 584), deep wound infection (ICD-9-CM code 958.3), pulmonary embolism (ICD-9-CM code 415), postoperative bleeding (ICD-9-CM codes 998.0, 998.1, and 998.2), and acute myocardial infarction (ICD-9-CM code 410).18-22 Admission to the intensive care unit, length of hospital stay, and medical expenditures after the index surgery were also compared. Postoperative adverse events noted included septicemia, pneumonia, urinary tract infection, and in-hospital mortality.
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TABLE 1. Characteristics of Pregnant and Nonpregnant Surgical Patientsa Patients (No. [%]) Nonpregnant (N¼22,364)
Characteristic Age (y) 18-24 25-29 30-34 35-39 40-44 45-50 Low income Operation in a medical center Types of nonobstetric surgery Digestive Musculoskeletal Kidney, ureter, bladder Respiratory Neurosurgery Breast Cardiovascular Skin Eye Others Types of anesthesia General Epidural or spinal Coexisting medical conditions Mental disorders Chronic obstructive pulmonary disease Hypertension Diabetes Hyperlipidemia Ischemic heart disease Epilepsy Liver cirrhosis Renal dialysis Congestive heart failure a
Pregnant (N¼5591)
3900 6688 7160 3276 872 468 568 8684
(17.4) (29.9) (32.0) (14.7) (3.9) (2.1) (2.5) (38.8)
975 1672 1790 819 218 117 142 2171
(17.4) (29.9) (32.0) (14.6) (3.9) (2.1) (2.5) (38.8)
9992 5324 1120 1120 904 852 696 500 172 1684
(44.7) (23.8) (5.0) (5.0) (4.0) (3.8) (3.1) (2.2) (0.8) (7.5)
2498 1331 280 280 226 213 174 125 43 421
(44.7) (23.8) (5.0) (5.0) (4.0) (3.8) (3.1) (2.2) (0.8) (7.5)
16,024 (71.7) 6340 (28.3) 2144 680 288 252 124 72 48 44 20 8
4006 (71.7) 1585 (28.3)
(9.6) (3.0) (1.3) (1.1) (0.6) (0.3) (0.2) (0.2) (0.1) (0.04)
536 170 72 63 31 18 12 11 5 2
(9.6) (3.0) (1.3) (1.1) (0.6) (0.3) (0.2) (0.2) (0.1) (0.04)
P>.99 for all characteristics.
Statistical Analyses Propensity score matched pairs analyses were used to determine associations between pregnancy and the primary outcome (in-hospital mortality after surgery). We developed a nonparsimonious multivariable logistic regression model to estimate a propensity score for pregnant surgical patients. Clinical significance guided the initial choice of covariates in this model: age, low income, medical center, types of nonobstetric surgery and anesthesia, mental disorders, chronic obstructive pulmonary disease, hypertension, diabetes, hyperlipidemia, ischemic heart disease, epilepsy, liver 1168
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cirrhosis, congestive heart failure, and renal dialysis. We matched pregnant women to nonpregnant women using a greedy matching algorithm (without replacement) with a caliper width of 0.2 SD of the log odds of the estimated propensity score. This method could remove 98% of the bias from measured covariates.23,24 Categorical variables are summarized using frequency (percentage) and were compared between pregnant and nonpregnant surgical patients using a c2 test. Continuous variables are summarized using mean SD and were compared using a t test. Logistic regression was used to calculate the odds ratios (ORs) and 95% CIs of postoperative complications and in-hospital mortality associated with pregnancy. Additional analyses stratified by age, number of medical conditions, and types of surgery were also performed to examine adverse events in pregnant women within these strata. RESULTS Table 1 shows the baseline characteristics of pregnant patients and controls who underwent nonobstetric surgery. After propensity score matching, there were no significant differences in groups of surgical patients with and without pregnancy analyzed by age, low income, whether the operation occurred in a medical center, types of nonobstetric surgery and anesthesia, mental disorders, chronic obstructive pulmonary disease, hypertension, diabetes, hyperlipidemia, ischemic heart disease, epilepsy, liver cirrhosis, renal dialysis, or congestive heart failure. Compared with nonpregnant patients, pregnant patients had higher risks of postoperative septicemia (OR¼1.75; 95% CI, 1.47-2.07), pneumonia (OR¼1.47; 95% CI, 1.01-2.13), urinary tract infection (OR¼1.29; 95% CI, 1.081.54), and in-hospital mortality (OR¼3.94; 95% CI, 2.62-5.92) (Table 2). Pregnancy was also associated with adverse events (OR¼1.63; 95% CI, 1.45-1.84) and admission to the intensive care unit (OR¼2.46; 95% CI, 2.22-2.73) after surgery. Mean SD medical expenditures ($3435$4943 vs $1891$3017; P<.001) and hospital length of stay (10.916.2 vs 5.89.5 days; P<.001) were comparatively greater for pregnant patients. In the stratification analysis, associations between pregnancy and postoperative adverse events were significant in women aged 18 to
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24 years (OR¼1.83; 95% CI, 1.37-2.44), 25 to 29 years (OR¼1.73; 95% CI, 1.40-2.14), 30 to 34 years (OR¼1.63; 95% CI, 1.32-2.01), and 35 years and older (OR¼1.40; 95% CI, 1.09-1.80) (Table 3). Pregnancy was also associated with postoperative adverse events in women who had no medical conditions (OR¼1.70; 95% CI, 1.50-1.93). Pregnant women who underwent cardiovascular surgery had the highest postoperative adverse event risk compared with nonpregnant women (OR¼2.98; 95% CI, 2.01-4.41). DISCUSSION In this nationwide retrospective cohort study, we analyzed reimbursement claims from Taiwan’s National Health Insurance Research Database and found increased risks of postoperative bleeding, septicemia, pneumonia, urinary tract infection, and in-hospital mortality after nonobstetric surgical procedures in pregnant women. The association between pregnancy and postoperative adverse events was most significant in women undergoing cardiovascular surgical procedures. This study had several strengths in addition to its large sample size and cohort study design. Various types of surgical procedures were analyzed, and a propensity score matching study design and multivariate adjustment also were used. Based on data from previous investigations,25-28 age, socioeconomic status, and level of hospital were associated with postoperative outcomes and thus should be considered as potential confounding factors when investigating associations between pregnancy and postoperative outcomes. In addition, previous studies identified coexisting medical conditions as independent determinants in perioperative complications and mortality, including hypertension,29 diabetes,18 mental disorders,19 congestive heart failure,30 chronic obstructive pulmonary disease,29 ischemic heart disease,29 hyperlipidemia,31 epilepsy,20 liver cirrhosis,21,31 and renal dialysis.22,29 To most accurately investigate postoperative outcomes in pregnant patients, we adjusted for sociodemographic features and coexisting medical conditions in the multivariate regression models. After adjustment for potential confounding factors, the present study found that pregnancy is an independent factor associated with postoperative Mayo Clin Proc. n September 2016;91(9):1166-1172 www.mayoclinicproceedings.org
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TABLE 2. Adverse Events After Nonobstetric Surgery in Pregnant and Nonpregnant Patientsa Adverse event Postoperative complications (%) Septicemia Pneumonia Urinary tract infection Stroke Deep wound infection Acute renal failure Acute myocardial infarction Postoperative bleeding Pulmonary embolism In-hospital mortality (%) ICU stay (%) Adverse events (%)c Medical expenditures ($), mean SD Length of hospital stay (d), mean SD
Nonpregnant patients
Pregnant patients
2.05 0.47 2.34 0.32 0.50 0.21 0.01 0.53 0.05 0.21 5.02 4.74 18913017
3.52 0.68 3.00 0.39 0.47 0.18 0.00 0.63 0.02 0.82 11.52 7.51 34354943
5.89.5
10.916.2
OR (95% CI)b 1.75 1.47 1.29 1.22 0.93 0.85
(1.47-2.07) (1.01-2.13) (1.08-1.54) (0.76-1.97) (0.61-1.42) (0.43-1.69) – 1.19 (0.81-1.73) 0.36 (0.05-2.82) 3.94 (2.62-5.92) 2.46 (2.22-2.73) 1.63 (1.45-1.84) P<.001 P<.001
ICU ¼ intensive care unit; OR ¼ odds ratio. Adjusted for age, low income, operation in a medical center, types of anesthesia and surgery, and coexisting medical conditions. c Adverse events include septicemia, pneumonia, urinary tract infection, and in-hospital mortality. a
b
in-hospital mortality, pneumonia, and septicemia after nonobstetric surgical procedures. We found effect of pregnancy on postoperative adverse events to be significant but varying by age group. Pregnant women 35 years and older still have increased odds of adverse events compared with nonpregnant women, but the odds of adverse events in this age group is lower than that of the 18- to 24-year old group. Previous studies investigated the effects of pregnancy in various clinical situations.2,4,32-34 Two studies found that pregnant women are less likely to be diagnosed as having acute appendicitis than are nonpregnant women.2,32 However, one large-scale investigation revealed that pregnancy may be a risk factor for increased severity of Crohn disease.35 Regarding the effect of pregnancy on the course and severity of breast cancer, various studies have claimed equivalent prognosis, protective effect, and harmful effect.4,33,34 The influence of pregnancy on maternal surgical outcome is still inconclusive.6-17 One study focusing on maternal surgical outcome after appendectomy and cholecystectomy found that pregnancy does not increase postoperative morbidity.12 A second population-based study also stated that
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TABLE 3. Risk of Postoperative Adverse Events in Pregnant and Nonpregnant Patients in a Stratification Analysis by Age, Medical Conditions, and Types of Surgerya Adverse events (No. [%])b
OR (95% CI)c
3900 975
163 (4.18) 72 (7.38)
1.00 (Reference) 1.83 (1.37-2.44)
6688 1672
308 (4.61) 129 (7.72)
1.00 (Reference) 1.73 (1.40-2.14)
7160 1790
326 (4.55) 129 (7.21)
1.00 (Reference) 1.63 (1.32-2.01)
4616 1154
263 (5.70) 90 (7.80)
1.00 (Reference) 1.40 (1.09-1.80)
18,960 4740
885 (4.67) 364 (7.68)
1.00 (Reference) 1.70 (1.50-1.93)
3404 851
175 (5.14) 56 (6.58)
1.00 (Reference) 1.30 (0.95-1.77)
7003 2030
460 (6.57) 182 (8.97)
1.00 (Reference) 1.40 (1.17-1.68)
5324 1329
123 (2.31) 55 (4.14)
1.00 (Reference) 1.83 (1.32-2.52)
Patients (No.) Age 18-24 y Not pregnant Pregnant Age 25-29 y Not pregnant Pregnant Age 30-34 y Not pregnant Pregnant Age 35 y Not pregnant Pregnant No medical conditions Not pregnant Pregnant 1 Medical conditions Not pregnant Pregnant Abdominal surgery Not pregnant Pregnant Musculoskeletal surgery Not pregnant Pregnant Cardiovascular surgery Not pregnant Pregnant Neurosurgery Not pregnant Pregnant Digestive surgery Not pregnant Pregnant
664 171
89 (13.40) 54 (31.58)
1.00 (Reference) 2.98 (2.01-4.4 1)
904 226
46 (5.09) 18 (7.96)
1.00 (Reference) 1.61 (0.92-2.84)
9992 2498
497 (4.97) 196 (7.85)
1.00 (Reference) 1.63 (1.37-1.93)
OR ¼ odds ratio. Adverse events include postoperative septicemia, pneumonia, urinary tract infection, and inhospital mortality. c Adjusted for age, low income, operation in a medical center, types of anesthesia and surgery, and coexisting medical conditions. a
b
pregnancy was not a significant predictor for having a surgical complication after cholecystectomy.10 Another study investigated complications after breast cancer surgery and also found similar outcomes between women with and without pregnancy.11 Nevertheless, in a study regarding thyroid and parathyroid surgery, pregnant women have worse clinical and economic outcomes than nonpregnant women.9 Although these studies provided some information, focusing only on specific types of surgery was their main limitation. Unlike these previous 1170
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investigations,6-17 the present study’s strengths were its large sample size, cohort study design, multivariate adjustment, and comparison of various types of surgery. Some possible explanations may clarify why pregnant women had increased postoperative complications and in-hospital mortality after nonobstetric surgical procedures. First, anatomic and physiologic changes during pregnancy may increase the complexity and difficulty of disease diagnosis and management.1,13 The possibility of delayed diagnosis or inappropriate management of surgical disease may consequently contribute to worse outcomes. Second, the “wait and see” strategy is commonly used in pregnant women to postpone invasive procedures to later in pregnancy or to the postpartum period.36 The policy of deferring surgical intervention may allow the surgical disease to progress. Another explanation is that pregnancy per se may influence the severity of some surgical disease,12,37,38 which may become more severe compared with the same condition in nonpregnant women when surgery is ultimately performed. More advanced surgical disease may result in worse postoperative outcomes. Third, pregnancy per se is a factor in increasing susceptibility to or severity of infectious diseases, including viral, bacterial, and parasitic infections; this is why we investigated increased postoperative septicemia in pregnant women.39 Finally, pregnant patients undergoing surgery may receive more attention and monitoring in the postoperative period, and, therefore, there is an increased possibility of longer hospitalization, admission to the intensive care unit, and higher medical expenditures. This study has some limitations. First, detailed socioeconomic and lifestyle information and data on severity of comorbid disease and biochemical measures were not available from Taiwan’s National Health Insurance Research Database. Second, information about pathology and details about the presentation or severity of the surgical disease could not be obtained. Therefore, the influence of surgical disease severity on maternal surgical outcome could not be optimally adjusted for. Third, because the database lacks records regarding gestational age and trimester of pregnancy, we could not investigate differences in postoperative outcome among the trimesters and validate the impact of surgical
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intervention in various trimesters. In addition, the coexisting medical conditions included in this study were based on previous surgical studies’ suggestions.18-22 That other coexisting diseases were not considered is one of the present study’s limitations. Finally, the definition of postoperative adverse events in this study included only pneumonia, septicemia, uninary tract infection, and in-hospital mortality; that it did not include all complications may be considered a study limitation. CONCLUSION This nationwide cohort study associated pregnancy with higher in-hospital mortality and risk of pneumonia, septicemia, and postoperative bleeding after nonobstetric surgery. These data suggest a need to provide better perioperative management and monitoring in this population to prevent or minimize postoperative complications. ACKNOWLEDGMENTS This study is based in part on data obtained from the National Health Insurance Research Database. This database is provided by the Bureau of National Health Insurance of Taiwan’s Ministry of Health and Welfare and is managed by the National Health Research Institutes. The authors’ interpretations and conclusions do not represent those of the Bureau of National Health Insurance, the Ministry of Health and Welfare, or the National Health Research Institutes. Prof. Ta-Liang Chen has equal contribution with the corresponding author. Abbreviations and Acronyms: ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification; ICU = intensive car unit; OR = odds ratio Affiliations (Continued from the first page of this article.): (W.-M.L.); Department of Surgery, China Medical University Hospital, Taichung, Taiwan (C.-C.Y.); Department of Surgery, University of Illinois, Chicago, IL, USA (C.-C.Y.); Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan (T.-L.C., C.-C.L.); Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan (T.-L.C., C.-C.L.); School of Chinese Medicine, China Medical University, Taichung, Taiwan (C.-C.L.) Grant Support: This study was supported in part by grants from Shuang Ho Hospital, Taipei Medical University (104TMU-SHH-23), Taiwan’s Ministry of Science and Technology (MOST104-2314-B-038-027-MY2; NSC1022314-B-038-021-MY3), and Taiwan’s Ministry of Health Mayo Clin Proc. n September 2016;91(9):1166-1172 www.mayoclinicproceedings.org
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and Welfare Clinical Trial and Research Center of Excellence (MOHW105-TDU-B-212-133019). Correspondence: Address to Chien-Chang Liao, PhD, MPH, or Ta-Liang Chen, MD, PhD, Department of Anesthesiology, Taipei Medical University Hospital, 252 Wuxing St, Taipei 110, Taiwan ([email protected]; [email protected]).
REFERENCES 1. Tan EK, Tan EL. Alterations in physiology and anatomy during pregnancy. Best Pract Res Clin Obstet Gynaecol. 2013;27(6):791-802. 2. Andersson RE, Lambe M. Incidence of appendicitis during pregnancy. Int J Epidemiol. 2001;30(6):1281-1285. 3. Neligan PJ, Laffey JG. Clinical review: special populations: critical illness and pregnancy. Crit Care. 2011;15(4):227. 4. Ali SA, Gupta S, Sehgal R, et al. Survival outcomes in pregnancy associated breast cancer: a retrospective case control study. Breast J. 2012;18(2):139-144. 5. Berry C, Ley EJ, Mirocha J, et al. Do pregnant women have improved outcomes after traumatic brain injury? Am J Surg. 2011;201(4):429-432. 6. Cohen-Kerem R, Railton C, Oren D, et al. Pregnancy outcome following non-obstetric surgical intervention. Am J Surg. 2005; 190(3):467-473. 7. Erekson EA, Brousseau EC, Dick-Biascoechea MA, et al. Maternal postoperative complications after nonobstetric antenatal surgery. J Matern Fetal Neonatal Med. 2012;25(12):2639-2644. 8. Abbasi N, Patenaude V, Abenhaim H. Management and outcomes of acute appendicitis in pregnancy-population-based study of over 7000 cases. BJOG. 2014;121(12):1509-1514. 9. Kuy S, Roman SA, Desai R, et al. Outcomes following thyroid and parathyroid surgery in pregnant women. Arch Surg. 2009; 144(5):399-406. 10. Kuy S, Roman SA, Desai R, et al. Outcomes following cholecystectomy in pregnant and nonpregnant women. Surgery. 2009; 146(2):358-366. 11. McMaster J, Dua A, Desai SS, et al. Short-term outcomes following breast cancer surgery in pregnant women. Gynecol Oncol. 2014;135(3):539-541. 12. Silvestri MT, Pettker CM, Brousseau EC, et al. Morbidity of appendectomy and cholecystectomy in pregnant and nonpregnant women. Obstet Gynecol. 2011;118(6):1261-1270. 13. Yates MT, Soppa G, Smelt J, et al. Perioperative management and outcomes of aortic surgery during pregnancy. J Thorac Cardiovasc Surg. 2015;149(2):607-610. 14. Jeong JS, Ryu DH, Yun HY, et al. Laparoscopic appendectomy is a safe and beneficial procedure in pregnant women. Surg Laparosc Endosc Percutan Tech. 2011;21(1):24-27. 15. Fardiazar Z, Derakhshan I, Torab R, et al. Maternal-neonatal outcome in pregnancies with non-obstetric laparotomy during pregnancy. Pak J Biol Sci. 2014;17(2):260-265. 16. Sadot E, Telem DA, Arora M, et al. Laparoscopy: a safe approach to appendicitis during pregnancy. Surg Endosc. 2010; 24(2):383-389. 17. Moore HB, Juarez-Colunga E, Bronsert M, et al. Effect of pregnancy on adverse outcomes after general surgery. JAMA Surg. 2015;150(7):637-643. 18. Yeh CC, Liao CC, Chang YC, et al. Adverse outcomes after noncardiac surgery in patients with diabetes: a nationwide population-based retrospective cohort study. Diabetes Care. 2013;36(10):3216-3221. 19. Liao CC, Chiu WT, Yeh CC, et al. Risk and outcomes for traumatic brain injury in patients with mental disorders. J Neurol Neurosurg Psychiatry. 2012;83(12):1186-1192. 20. Chang CC, Hu CJ, Lam F, et al. Postoperative adverse outcomes in surgical patients with epilepsy: a population-based study. Epilepsia. 2012;53(6):987-994.
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