Materials and Methods
We conducted a retrospective population-based cohort study utilizing data from the Health Care Cost and Utilization Project-Nationwide Inpatient Sample database (HCUP-NIS) over a period of 11 years, from 2004 to 2014. The HCUP-NIS is the largest inpatient sample database in the United States and is comprised of hospital inpatient stays submitted by hospitals throughout the entire country. Each year, the database provides information relating to 7 million inpatient stays, including patient characteristics, diagnosis, and procedures. The data represent more than 97% of inpatient discharges from community hospitals. A cohort of deliveries between 2004 and 2014 inclusively was created, using international classification of diseases, ninth edition, Clinical Modification (ICD-9-CM) diagnostic codes: 634x-679x, V22x, V23x, or V27x, and ICD-9-CM procedural codes: 72x -75x. Furthermore, the cohort was limited to admissions that resulted in a delivery or a maternal death using ICD-9-CM codes: 650x, 677x, or 651x-676x, and ICD-9-CM procedure codes: 72x, 73x, 74.0, 74.1, 74.2, 74.4 or 74.99, so that each subject was included once per pregnancy. Women with DS were identified using ICD-9 code 758.0, all women negative for DS comprised the control group. ICD-9 codes were also used to identify demographic characteristics, as well as pregnancy, delivery, and neonatal outcomes. Baseline clinical characteristics included age, race, income, insurance type, hospital type, previous Cesarean section (C/S), multiple gestations, tobacco use, obesity defined as body mass index (BMI) ≥30 kg/m2, as well as pre-gestational hypertension (HTN), diabetes, and thyroid disease. Pregnancy outcomes included gestational diabetes, Placenta previa, and pregnancy-induced hypertension as a group of gestational hypertension, preeclampsia, eclampsia, and preeclampsia and eclampsia superimposed on underlying hypertension. Delivery outcomes included preterm delivery, preterm premature rupture of membrane (PPROM), abruption placenta, chorioamnionitis, mode of delivery, wound complication, maternal infection, hysterectomy, blood transfusion, venous thromboembolism (VTE), and maternal death. Maternal infections were composed of chorioamnionitis, septicemia during labor, postpartum endometritis, septic pelvic, or peritonitis. Wound complications were defined as infection, hematoma, hemorrhage or disruption of C/S or perineal wound. VTE included deep vein thrombosis (DVT) and pulmonary embolism during pregnancy, intrapartum or in the postpartum period. The neonatal outcomes included small for gestational age (SGA), congenital anomalies, and intrauterine fetal demise (IUFD). An initial analysis was performed to identify the prevalence of pregnant women with DS per year over the entire duration of the study. We compared the demographic and clinical characteristics of women with DS to those without DS by using Chi-square tests. Pregnant women with DS (study group) were matched based on age and health insurance type to women without DS (control) at a ratio of 1:4. Subsequently, multivariate stepwise logistic regression analyses were conducted to explore associations between DS and maternal and neonatal obstetrical outcomes through the calculation of odds ratios (OR) and 95% confidence intervals (CI). The regression models were adjusted for the potential confounding effects of maternal baseline clinical characteristics that were statistically different (p ≤ 0.05) per group. All analyses were performed using SPSS 23.0 (IBM Corporation, Chicago, USA) software. This study used exclusively publicly accessible, anonymized data; hence, according to articles 2.2 and 2.4 of Tri-Council Policy statement (2010), institutional review board approval was not required.