Original article
Neurodevelopment in the offspring of Japanese systemic lupus erythematosus patients

https://doi.org/10.1016/j.braindev.2009.06.006Get rights and content

Abstract

Objective: To evaluate pregnancy outcome of systemic lupus erythematosus (SLE) and the neuropsychological outcomes in offspring of SLE mothers. Study design: Pregnancy outcomes of SLE patients from 1989 to 2006 were determined and the neuropsychological development of the children born to SLE patients was examined suited for their age; Bayley Scales of Infant Development up to four years and Kauffmann Assessment Battery for Children from four years onwards. Results: Of the 233 deliveries, 58 (24.7%) were preterm, 72 (30.9%) were low-birth-weight, and 46 (19.7%) were IUGR. Twenty-six children enrolled in this study had normal intelligence. The mean MDI and PDI were 95.8 ± 10.1 and 94.6 ± 14.1, respectively. The mean scores for the Sequential Processing scale, Simultaneous Processing scale, and Mental Processing composite were 103.1 ± 13.3, 104.2 ± 10.2, and 104.2 ± 12.2, respectively. In the children with anti-Ro/SS-A antibody-positive mothers, mean gestational age and birth weight were significantly lower (p < 0.05), as a result, the mean score of Sequential Processing and Mental Processing were significantly lower than that of negative mothers. The presence of maternal antiphospholipid antibody was not related to gestational age, birth weight and any score on the intelligence tests, except for the rate of IUGR. Conclusion: The rates of preterm delivery and IUGR were frequent in the SLE patients and careful monitoring and management of the disease during pregnancy are still necessary. We should examine the neurodevelopment of the children born from mothers with anti-Ro/SS-A antibody prospectively.

Introduction

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that occurs mainly in women during their childbearing years. The results of pregnancies in women with SLE were once discouraging because of the possible worsening of the disease and negative effects on fetal outcome [1]. Recently, however, the diagnosis and management of SLE have improved greatly. As a result, the disease can now be controlled sufficiently and SLE patients are not discouraged from bearing children. Therefore, an increasing number of women with SLE are becoming pregnant.

However, for SLE patients, the pregnancy outcome commonly includes preterm delivery (21–52%), intrauterine growth retardation (10–30%), and pregnancy loss (10–50%) [2], [3]. In particular, women with antiphospholipid antibodies tend to experience recurrent miscarriage and fetal death. Maternal anti-Ro/SS-A antibodies confer a risk of developing congenital heart block (CHB) in the fetus and other clinical manifestations in newborns such as skin rashes, hepatic abnormalities, and thrombocytopenia, which are generally referred to as neonatal lupus syndrome (NLS).

Now that many women with SLE can expect a safe pregnancy and delivery, they are becoming more interested in the healthy growth and development of their children, rather than the pregnancy itself. Previous studies on the long-term neuropsychological development of children of SLE mothers show that their level of intelligence is normal, but they are more like to have developmental disorders, especially in males, such as left handedness, attention deficit, dyslexia, and learning disabilities (LD) compared to children of mothers who do not have SLE [4], [5]. Neri et al. [6] studied neuropsychological development using intelligence tests and specific tests for LD in the children of SLE patients; all children had normal IQs, but 14% of the school-aged children were diagnosed as dyslexic, suggesting that the occurrence of LD is associated with maternal antiphospholipid antibodies.

We investigated retrospectively the pregnancy outcome of SLE patients attending our hospital and evaluated the neuropsychological development of the children born to SLE patients with assessments suitable for their age. We focused on the relationship between developmental outcome and maternal autoantibodies during pregnancy.

Section snippets

Mothers: the pregnancies

Between 1998 and 2006, we delivered 233 SLE patients at Juntendo University Hospital, Tokyo, Japan. Our hospital is a tertiary medical care center and has experience with pregnancies in mothers with autoimmune diseases. All of the patients met the adjusted American College of Radiology (ACR) classification criteria for SLE. They were also informed about the criteria for the admission of SLE pregnancies at our institution (Table 1) and underwent blood examinations and echography by experienced

Pregnancy outcomes

In the 19 years between 1989 and 2006, we delivered 233 SLE patients at our Hospital. Preterm birth and IUGR were frequent: 58 (24.8%) were preterm, 72 (30.9%) were low-birth-weight, and 46 (19.7%) were IUGR. The mean maternal age was 31.5 years (range 19–40). The mean birth weight and gestational age were 2563 g (range 338–3740) and 37.4 weeks (range 24.7–41.3), respectively. Five children developed neonatal lupus syndrome (NLS): two with congenital heart block (CHB) and three with skin erythema.

Discussion

The overall prevalence of pregnancy outcomes in SLE patients was similar to those in previous reports. The rates of preterm delivery and IUGR were 24.8% and 19.7%, respectively, which fall within the reported ranges [10], [11]. The rates of preterm delivery and IUGR are affected by the disease activity, maternal antiphospholipid antibodies, and drugs such as high doses of corticosteroids or immunosuppressive drugs, which cause ovarian insufficiency, hypertensive complications in the second

Acknowledgement

We are indebted to Professor Yoshinari Takasaki; Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan; for his advice on the autoimmune diseases, to Dr Toshitaka Tanaka; Department of Obstetric and Gynecology, Juntendo University School of Medicine; for his help in the investigation of pregnancy outcomes. We also wish to acknowledgement all the families for their kind participation in our study.

Sponsor and grant: We had no any grant and sponsor

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