Background/Purpose: Women with SLE are at increased risk for pregnancy complications and specific autoantibodies may result in preferential loss of female offspring. Studies on the male to female (M:F) sex ratio of births in the SLE population have been contradictory. We used a large national population-based cohort of patients with SLE to determine whether the M:F ratio of births to mothers with SLE is different than the general population as well as a population of women with rheumatoid arthritis (RA) to estimate the ratio in another chronic inflammatory disease.

Methods: SLE was defined as ≥2 visits in inpatient or outpatient care (National Patient Register (NPR); 1969-2011) listing an SLE ICD code with ≥1 SLE-coded visit to a specialist. A sample of general population comparators was identified from the Total Population Register. Women with a delivery were identified from the Swedish Medical Birth Register (1973-2011). We used modified Poisson regression with robust sandwich estimators to calculate the risk ratio (RR) for having a male offspring associated with an SLE diagnosis adjusted for age, year and maternal country of birth. Our primary analysis was restricted to first singleton births only. In secondary analyses, we examined all births and restricted to live births only. We also examined antiphospholipid syndrome (APS) history in the SLE population using any ICD10 code before or at delivery, restricted to ≥1997 when the code was available. Lastly, we calculated the M:F ratio of offspring born to women with ≥2 RA-coded visits in the NPR with ≥1 visit to a specialist before delivery.

Results: We identified 604 women with SLE before their first delivery and 1289 singleton deliveries total to women with prevalent SLE. Maternal SLE at delivery had a lower proportion of male offspring compared to the general population. The RR for male offspring associated with SLE was 0.95 (95%CI 0.88, 1.04) for first births and 0.96 (95%CI 0.90, 1.01) for all singleton births (Table). RRs did not change with adjustment by age, year or country of birth. Results were similar among live births only and including multiples. Women with both APS and SLE had a lower odds of having a male child compared to the general population. We identified 1136 women with prevalent RA at first delivery and 2674 singleton deliveries total. The M:F ratio in RA was not significantly different than the general population (first birth RR=0.96 (95%CI 0.91, 1.02), all births OR=0.99 (95%CI 0.95, 1.03)).

Conclusion: We observed a lower proportion of male offspring born to women with prevalent SLE at delivery compared to the general population, which was not statistically significant. We observed a significantly lower odds of male offspring born to women with SLE and APS when all births were considered. In this large study using similar techniques to identify patients as that of a group in Canada, we did not confirm their findings of a male dominance in offspring.

Table. Maternal characteristics and M:F sex ratio among deliveries in Sweden, 1973-2011, comparing mothers with SLE at delivery to mothers from the general population restricted to singleton births
	First births			All births
	Prevalent SLE		General	Prevalent SLE		General
	at delivery		Population	at delivery		Population
N	604		18,226	1,289		45,185
Male baby, N (%)	293 (48.5)		9,303 (51.0)	631 (49.0)		23,204 (51.4)
M:F ratio	0.94		1.04	0.96		1.06
Mother born in Sweden, N (%)	542 (89.7)		16,314 (89.5)	1,145 (88.8)		39,927 (88.4)
Mother’s age, mean (SD)	28.7 (4.6)†		26.5 (5.1)	30.4 (4.8)†		28.8 (5.3)
Stilllbirth*, N (%)	7 (1.2)†		75 (0.41)	12 (0.93)†		173 (0.4)
Male baby, of live births, N (%)	290 (48.6)		9,265 (51.0)	627 (49.1)		23,113 (51.4)
RR¥ (95%CI)	0.95 (0.88, 1.04)		1.0 (ref)	0.96 (0.90, 1.01)		1.0 (ref)
Births 1997-2011φ	SLE and APS+	SLE and APS-		SLE and APS+	SLE and APS-
RR(95%CI)	0.80 (0.50, 1.25)	0.96 (0.86, 1.08)	1.0 (ref)	0.69 (0.51, 0.94)	0.97 (0.90, 1.05)	1.0 (ref)
* fetal death before delivery or during delivery
† significant at alpha=0.05, chi-square test for proportions, 2-sided t-test for means
¥ RR for having a male offspring associated with a maternal SLE diagnosis
φ Presenting RR and 95% CI, restricted to 1997 onwards to account for ICD10 coding of APS.

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