Risk factors for adverse pregnancy outcomes in women with rheumatoid arthritis and follow-up of their offspring

Luo, Liang; Li, Xuerong; Yan, Rui; Zhang, Huijuan; Li, Chun

doi:10.1007/s10067-022-06233-9

Cited by 3 publications

(3 citation statements)

References 40 publications

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“…Previous studies have reported that previous miscarriages, antinuclear antibody positivity and high activity of RA were risk factors for APOs. 33 34 Overall, this suggests that patients with RA should consult their physician about planning for pregnancy, including the discontinuation of teratogenic drugs.…”

Section: Discussionmentioning

confidence: 99%

Medication utilisation trends during pregnancy and factors influencing adverse pregnancy outcomes in patients with rheumatoid arthritis

Song,

Cho,

Jung

et al. 2024

RMD Open

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ObjectivesWe aimed to investigate medication utilisation trends during pregnancy and identify factors associated with adverse pregnancy outcomes (APOs) in patients with rheumatoid arthritis (RA).MethodsFemale patients with RA aged 20–50 years were identified from the Korean national health insurance database between 2010 and 2020. Pregnancy episodes were divided into two groups according to pregnancy outcome: the delivery group and the APO group (abortion and stillbirth). The characteristics and medication utilisation patterns were compared between the two groups, and multivariable logistic regression analysis was conducted to identify the factors associated with APOs.ResultsA total of 5728 pregnancy episodes were included, comprising 4576 delivery episodes and 1152 APO episodes. The mean maternal age for all pregnancy episodes was 33.7 years; 33.3 years in the delivery group and 33.7 years in the APO group. Hydroxychloroquine was the most commonly used conventional synthetic disease-modifying antirheumatic drug (DMARD) during the preconception period and pregnancy in both groups. The prescription rate of all DMARDs decreased rapidly during pregnancy. In the multivariable analysis, use of methotrexate (adjusted OR (aOR): 2.14, 95% CI 1.57 to 2.92) and leflunomide (aOR: 2.68, 95% CI 1.39 to 5.15) within 3 months before conception was associated with APOs.ConclusionMethotrexate and leflunomide are associated with an increased possibility of APOs, emphasising the importance of appropriate medication adjustment when planning for pregnancy.

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Section: Discussionmentioning

confidence: 99%

Medication utilisation trends during pregnancy and factors influencing adverse pregnancy outcomes in patients with rheumatoid arthritis

Song,

Cho,

Jung

et al. 2024

RMD Open

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“…This makes GC a widely used therapy for women at risk of preterm birth to accelerate the maturation of fetal organs. Meanwhile, GC is also a first-line and compulsory treatment for pregnant women with asthma [ 17 ] or an autoimmune disease [ 18 , 19 ], throughout the entire pregnancy until labor.…”

Section: Introductionmentioning

confidence: 99%

Hypermethylation of the Bmp4 promoter dampens binding of HIF-1α and impairs its cardiac protective effects from oxidative stress in prenatally GC-exposed offspring

Gao¹,

Yuan²,

Zhang

et al. 2023

Cell. Mol. Life Sci.

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The exposure to an unhealthy environment in utero can lead to the occurrence of cardiovascular diseases in the offspring. Glucocorticoids (GC) are essential for normal development and maturation of fetal organs and is a first-line treatment for pregnant women affected by autoimmune diseases. However, excess prenatal GC exposure might program the development of fetal organs and cause a number of chronic diseases in later life. Our previous studies indicated that cardiac functions were significantly compromised in rat offspring prenatally exposed to the synthetic glucocorticoid dexamethasone (DEX), only after ischemia–reperfusion. In the present study, we further observed that DNA hypermethylation of bone morphogenetic protein 4 (Bmp4) promoter in cardiomyocytes caused by prenatal DEX exposure substantially dampened the binding activity of transcription factor HIF-1α induced by cardiac ischemia. Therefore, prenatal DEX exposure inhibits the induction of BMP4 upon I/R and attenuates the protective effects of BMP4 in cardiomyocytes, which eventually manifests as malfunction of the adult heart. Moreover, we employed two cardiac-specific Bmp4 knock-in mouse models and found that in vivo BMP4 overexpression could rescue the cardiac dysfunction caused by prenatal GC exposure. In depth mechanistic research revealed that BMP4 protects the cardiomyocytes from mitophagy and apoptosis by attenuating mitochondrial PGC-1α expression in a p-Smad and Parkin-dependent manner. These findings suggest that prenatal GC exposure increases the susceptibility of the offspring’s heart to a “second strike” after birth, due to the failure of hypoxia-induced HIF-1α transactivation of the hypermethylated Bmp4 promoter in cardiomyocytes. Pretreatment with the DNA methylation inhibitor, 5-Aza-2′-deoxycytidine, could be a potential therapeutic method for this programming effect of GC exposure during pregnancy on neonatal cardiac dysfunction.

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“…There is evidence that the musculoskeletal system diseases in pregnant women are associated with negative perinatal consequences (preeclampsia, premature birth, fetal growth retardation, postpartum hemorrhage, etc.) [16,17].…”

Section: Introductionmentioning

confidence: 99%

The musculoskeletal system diseases in pregnant women with high infection risk and the single nucleotide rs1544410 polymorphism of the calcitriol receptor gene

Manasova

Диденкул

Zhovtenko

et al. 2023

PJS

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Background. The problem of vitamin D (VD) deficiency in the population, in general, and in pregnant women, in particular, and related diseases, including the musculoskeletal system, remains one of the most widespread medical and social problems of our time. The purpose was to determine the frequency of musculoskeletal diseases in pregnant females at high infection risk (HIR) with impaired vitamin D status and single-nucleotide Bsml polymorphism of its receptor gene. Materials and methods. Fifty-six pregnant women (main group) with HIR and 40 healthy pregnant women (control group) had been examined. The level of 25-hydroxyvitamin D (25(OH)D) in blood was determined by the enzyme-linked immunosorbent assay, and real-time polymerase chain reaction was used to detect the mutant version of Bsml (rs1544410) polymorphism of the gene that is encoding vitamin D receptors (VDR). Statistical processing of the results was done using the resource www.socscistatistics.com. Results. HIR was due to the presence of chronic kidney diseases, carriers of pathogens of the TORCH group of infections and conditionally pathogenic microflora in the urogenital tract. The level of 25(OH)D was lower than the generally accepted optimal level in 76.8 and 15 % of pregnant women, in the main and control groups, respectively (F = 0.03; p = 0.0001). Carriers of the heterozygous genotype A/G were 67.7 % of pregnant women with HIR compared to 35 % of the control group (odd ratio (OR) = 3.95; 95% confidence interval (CI): 2.19–7.1; χ2 = 20.88, p = 0.00001), and the G/G genotype was inherent in 19.6 and 47.5 % of women, respectively (OR = 0.27; 95% CI 0.15–0.51; p = 0.00006). A third of pregnant women from the main group had a history of musculoskeletal diseases (32.14 %) versus 12.5 % in control group (OR = 3.15; 95% CI: 1.54–6.46); 71.4 % of pregnant women with HIR were carriers of A/G genotype (OR = 9.79; 95% CI: 5.10–18.82). Conclusions. The share of vitamin D deficiency/insufficiency in pregnant women with HIR is almost 77 %. The general somatic history of these women is characterized by a high frequency of the kidney diseases (37.5 %) and musculoskeletal diseases (32.1 %). Two-thirds of pregnant women with HIR, as well as with musculoskeletal diseases, are carriers of the heterozygous Bsml of polymorphic genotype A/G of the VDR gene, which probably causes a higher risk of the development of pathology in conditions of calcitriol deficiency. Studying VD status, the genetic personification of disease risks, and correction of modified factors in time, in particular, VD deficiency is seen as a promising direction for improving perinatal outcomes and the quality of life of pregnant women in general, but further research is required.

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Risk factors for adverse pregnancy outcomes in women with rheumatoid arthritis and follow-up of their offspring

Cited by 3 publications

References 40 publications

Medication utilisation trends during pregnancy and factors influencing adverse pregnancy outcomes in patients with rheumatoid arthritis

Medication utilisation trends during pregnancy and factors influencing adverse pregnancy outcomes in patients with rheumatoid arthritis

Hypermethylation of the Bmp4 promoter dampens binding of HIF-1α and impairs its cardiac protective effects from oxidative stress in prenatally GC-exposed offspring

The musculoskeletal system diseases in pregnant women with high infection risk and the single nucleotide rs1544410 polymorphism of the calcitriol receptor gene

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