Preterm birth phenotypes in women with autoimmune disease

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Women with autoimmune rheumatic diseases have an elevated risk of various preterm birth (PTB) phenotypes, according to a large population-based, retrospective cohort study. Hence, the study in BJOG strongly advocates preconception counseling and close monitoring during pregnancy.

Methods
All live singleton births in California between 2007 and 2011 were analyzed, representing maternally linked hospital and birth certificate records of 2,481,516 deliveries. Patients with five prevalent autoimmune rheumatic diseases at the time of delivery were identified by ICD‐9 codes: systemic lupus erythematosus (SLE) (n = 2,272); systemic sclerosis (SSc) (n = 88); rheumatoid arthritis (RA) (n = 1,501); polymyositis/dermatomyositis (DM/PM) (n = 38); and juvenile idiopathic arthritis (JIA) (n = 187).

PTB was defined as birth between 20 weeks and less than 37 gestational weeks, based on the obstetric estimate. It was also subcategorized by gestational age: early (20 to less than 32 weeks) and late (32 to less than 37 weeks). PTB was due to either preterm premature rupture of membranes (PPROM), spontaneous, or medically indicated.

The investigators compared patients with autoimmune disease to the general obstetric population, while adjusting for maternal age, race/ethnicity, body mass index (BMI), smoking, education, payer, parity and prenatal care.

Results
Patients with autoimmune disease had an increased relative risk (RR) for PTB for each of the five autoimmune diseases evaluated: SLE (RR 3.27; 95% confidence interval [CI]: 3.01 to 3.56); RA (RR 2.04; 95% CI: 1.79 to 2.33), SSc (RR 3.74; 95%CI: 2.51 to 5.58); JIA (RR 2.23; 95% CI: 1.54 to 3.23); and DM/PM (RR 5.26; 95%CI: 3.12 to 8.89).

“These elevated risks were observed for the majority of preterm birth phenotypes as well,” wrote the authors from Stanford University School of Medicine.

At least 90% of the women with maternal autoimmune disease started prenatal care within the first 5 months of pregnancy and were nonsmokers. In addition, 64.7% of these women were nulliparous. Furthermore, women with autoimmune diseases were more likely to be non-Hispanic White, with the exception of those with SLE.

Results (cont.)
Women with autoimmune diseases also had a higher incidence of pre-existing hypertension, pregnancy-induced hypertension, pre-existing diabetes and gestational diabetes compared to the general obstetric population. However, for SLE, the rate of gestational diabetes was similar for the two groups: 7.22% vs. 7.17%.

But women with SLE had a higher risk for early overall PTB, as well as for medically indicated and spontaneous PTB, compared to corresponding late PTB phenotypes. Women with DM/PM and SSc also trended toward a comparable higher risk for many early preterm phenotypes as opposed to late preterm phenotypes.

For the autoimmune disease cohort as a whole, the frequencies of preeclampsia/eclampsia; small for gestational age/intrauterine growth restriction; and a placental abruption, complicated medically indicated preterm birth were 21.4%, 16.2% and 3.9%, respectively.

Furthermore, the relative risk of any form of preeclampsia was significantly elevated for each of the five autoimmune diseases, with risk of severe preeclampsia particularly high among women with SLE (RR 4.5; 95% CI: 3.7 to 5.4) and with SSc (RR 6.1; 95% CI: 2.7 to 13.5). Multiparous women with SLE also showed a higher risk of preeclampsia than in nulliparous women.

One study limitation is the reliance on ICD-9 codes, which may have resulted in misclassification. Also, the positive predictive value for the maternal diagnosis of SLE is only 50% to 60% with physician billing and hospital discharge.