Obstetric and neonatal complications among women with autoimmune disease
Introduction
The worldwide estimated cumulative prevalence of autoimmune disease is approximately 5% [1], and increasing [2]. Approximately 66% of autoimmune diseases have a mean age of onset less than 50 years [1], and 80% of autoimmune cases in the U.S. occur among women [3,4]. It is important to understand the effect autoimmune diseases have on pregnant women and their infants.
The physiologic regulation of inflammation during pregnancy plays an important function in obstetric and neonatal outcomes. Inflammation, an immune-mediated response, assists in implantation and placentation early in pregnancy. Inflammation also promotes parturition and placental expulsion [5]. Later in gestation, pro-inflammatory processes at the maternal/fetal interface due to infection or placental abruption may lead to preterm birth, preeclampsia, and other adverse outcomes [6]. Research into the etiology of these outcomes is warranted. Inflammation is a key feature of autoimmune disease [3,4,7]. However, the population-level impact of autoimmune diseases on pregnancy remains understudied. Our previous work found women with asthma or thyroid disease had an increased risk for poor obstetric and infant outcomes [[8], [9], [10]], yet not all cases of asthma or thyroid disease are autoimmune. The underlying biologic mechanisms linking autoimmune disease and increased risk of adverse obstetric and neonatal outcomes are not well understood yet may result from overlapping physiologic adaptations necessary for pregnancy [11,12], their disease states [[13], [14], [15], [16], [17], [18], [19], [20]], the presence of autoantibodies or medications [21,22] required for management during pregnancy [17,21,23,24].
A challenge in studying the association of autoimmune diseases with obstetric and neonatal outcomes is the rarity of both. Research conducted to date is largely among homogenous populations outside the U.S. [[14], [15], [16], [17],22,[25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41]]. Studies conducted among U.S. populations are often limited by small sample sizes [21,30,40] or focused on a specific autoimmune disease and lacked detailed data on multiple obstetric and infant outcomes [34,42,43].
Cesarean delivery and preterm delivery are most frequently examined in the existing literature. Women with type 1 diabetes mellitus (T1DM) [12,32,41,44], systemic lupus erythematosus (SLE) [[45], [46], [47], [48]], Crohn's disease [[49], [50], [51], [52]] or rheumatoid arthritis (RA) [22,53,54] are reported to be at increased risk for cesarean delivery but evidence among women with multiple sclerosis (MS) is mixed. Two population-based studies found women with MS had approximately 40% higher risk for cesarean delivery [27,28], while two other population-based studies [26,55] and two small case-control studies [25,56] found no increased risk. In addition, prior studies did not explore the indications or timing of cesarean deliveries (prelabor or intrapartum).
Similarly, evidence among women with T1DM [14,44], SLE [18,57], Crohn's [52,58,59] or RA [18,31,34] suggests increased risk of preterm birth while reports of preterm birth risk among women with MS are inconsistent. Two population-based studies report an increased preterm birth risk among women with MS [27,28], and four other studies report no increased risk [25,26,29,30]. No data are available regarding precursors of preterm birth or spontaneous versus induced deliveries among women with autoimmune disease.
Evidence for other prevalent complications associated with autoimmune disease is also inconclusive. For example, among women with RA, four studies report an increased risk of small for gestational age (SGA) [21,31,32,60], while four studies report no increased risk of SGA [16,22,33,34]. Evidence regarding neonatal intensive care unit (NICU) admission is also sparse with mixed results [[15], [16], [17],22,33,[35], [36], [37], [38], [39], [40]]. For certain autoimmune diseases like T1DM, and Crohn's disease, studies are limited and none have been conducted among US populations [14,15,39,41].
Using a nationwide US cohort, we aimed to provide a more comprehensive description of the obstetric and neonatal risks among women with autoimmune disease and their infants. To better understand obstetric and neonatal risks associated with maternal autoimmune disease, we examined women in the Consortium on Safe Labor (CSL) diagnosed with T1DM, SLE, Crohn's, MS, or RA. These diseases are heterogeneous and their target tissues vary (pancreatic β-cells for T1DM [61]; various tissues including musculoskeletal, renal, and central nervous system for SLE [62]; bowel in Crohn's [63]; the nervous system in MS [64]; and musculoskeletal system in RA [65]).
Section snippets
Consortium on Safe Labor
The CSL was a U.S. retrospective cohort study from 2002 to 2008 that abstracted labor and delivery information from electronic medical records from 19 U.S. hospitals. Data extracted for deliveries at 23 gestational weeks or later (n = 228,438) included: maternal sociodemographic characteristics, medical, reproductive and prenatal history, labor and delivery summaries, postpartum and newborn data [66]. For these analyses, we excluded multifetal pregnancies (n = 5,063, 2.2%), mothers with thyroid
Prevalence of autoimmune diseases
The prevalence of autoimmune diseases (cases per 1000 pregnancies) for the CSL population by demographic variables are presented in Table 1.
Black women had the highest rates of T1DM (2.9/1000) and SLE (1.3/1000), while white women had the highest rates of Crohn's (1.4/1000), MS (1/1000), and RA (0.8/1000). Women with private insurance had the highest rates of SLE (1.1/1000), Crohn's (1.1/1000), and MS (0.9/1000). Women with public insurance had the highest rate of T1DM (2.9/1000). Rates of
Discussion
Despite advances in management of autoimmune disease that aid women in fulfilling family plans, pregnant women with autoimmune diseases continue to experience increased risk of poor obstetric and neonatal outcomes. We found the risk for cesarean delivery after spontaneous or induced labor was similar among women with T1DM. However, the increased risk of overall cesarean delivery for women with SLE, Crohn's, MS or RA may have been due to increased risk of cesarean delivery after spontaneous
Conflicts of interest
Authors report no conflict of interest.
Source of funding
This research was supported by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), including funding for the Consortium on Safe Labor (Contract No. HHSN267200603425C) and the Air Quality and Reproductive Health Study (Contract No. HHSN275200800002I, Task Order No. HHSN27500008). This paper has been cleared for publication by the NICHD but the funding source had no role in the design,
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