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.