Altered DNA methylation in children born to mothers with rheumatoid arthritis during pregnancy

Ince-Askan, Hilal; Mandaviya, Pooja R.; Felix, Janine F.; Duijts, Liesbeth; Meurs, Joyce B. J. van; Hazes, Johanna M. W.; Dolhain, Radboud J E M

doi:10.1136/annrheumdis-2018-214930

Cited by 10 publications

(7 citation statements)

References 70 publications

(82 reference statements)

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Section: Discussionmentioning

confidence: 99%

“…An alternative, but not mutually exclusive, hypothesis could be that treatment with TNFi during pregnancy is able to induce epigenetic changes in the fetus, which positively influence fetal growth. In this respect, it has been shown that RA during pregnancy, either related to the disease itself, disease activity or medication, is associated with marked epigenetic changes in the offspring 25. In addition, in several populations of healthy mothers and their children, it has been shown that DNA-methylation in the newborn is associated with birth weight 26…”

Section: Discussionmentioning

confidence: 99%

“…In this respect, it has been shown that RA during pregnancy, either related to the disease itself, disease activity or medication, is associated with marked epigenetic changes in the offspring. 25 In addition, in several populations of healthy mothers and their children, it has been shown that DNA-methylation in the newborn is associated with birth weight. 26 Previous literature shows that TNFi use during pregnancy in patients with a chronic inflammatory conditions is associated with an increased risk of birth via elective and emergency CS.…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

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Tumour necrosis factor inhibitor use during pregnancy is associated with increased birth weight of rheumatoid arthritis patients’ offspring

et al. 2022

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ObjectivesTo study pregnancy outcomes in a closely monitored, well-defined cohort of women with rheumatoid arthritis (RA). In particular, pregnancy outcomes of women that used a TNFi during pregnancy.MethodsPatients were derived from a prospective study on pregnancy and RA (Preconception Counseling in Active RA study) and treated according to a treatment protocol aimed at minimal disease activity. Multivariate linear regression analysis was used to describe which variables influenced birth weight.Results188 patients were included, 92 (48.9%) patients with RA used a TNFi during pregnancy. Disease Activity Score in 28 joints C reactive protein (DAS28CRP) was low at all time points during pregnancy (DAS28CRP in the third trimester: 2.17 (SD 0.73). TNFi use was not associated with an increase of adverse pregnancy outcomes such as low birth weight (<2500 g), (emergency) caesarian section, hypertensive disorders or congenital malformations. TNFi use resulted in less children born small-for-gestational age (p=0.05), however, did not increase the risk of large-for-gestational age (p=0.73). Mean birth weight was 173 g higher in women that used a TNFi during pregnancy (3.344 kg vs 3.171 kg, p=0.03). In the multivariate analysis, maternal age (β −0.023, 95% CI −0.040 to –0.0065, p=0.007), TNFi use (β 0.20, 95% CI 0.066, 0.34, p=0.004), diabetes mellitus (β 0.37, 95% CI 0.12, 0.63, p=0.004) and gestational age (β 0.18, 95% CI 0.15, 0.2, p<0.001) were statistically significant associated with birth weight.ConclusionsThis is the first study to show that TNFi use during pregnancy is associated with increased birth weight of offspring of women with well-controlled RA. The underlying mechanism of TNF-inhibition on birth weight and the long-term consequences for the offspring should be explored in future research.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Rheumatoid Arthritismentioning

confidence: 99%

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Tumour necrosis factor inhibitor use during pregnancy is associated with increased birth weight of rheumatoid arthritis patients’ offspring

et al. 2022

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“…It can be speculated that DNA methylation could influence the long-term outcome of these children and open new interesting scenarios. It remains unknown whether the identified associations are causal, and if so, whether they are caused by either the disease or the treatment during pregnancy ( Ince-Askan et al, 2019b ).…”

Section: The Long-term Outcome Of Children Born To Women With Inflammmentioning

confidence: 99%

The Influence of Treatment of Inflammatory Arthritis During Pregnancy on the Long-Term Children’s Outcome

et al. 2021

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The management of reproductive issues in women with inflammatory arthritis has greatly changed over decades. In the 1980–1990s, women with refractory forms of arthritis were either not able to get pregnant or did choose not to get pregnant because of their disabling disease. Hence, the traditional belief that pregnancy can induce a remission of arthritis. The availability of biologic agents has allowed a good control of aggressive forms of arthritis. The main topic of discussion during preconception counselling is the use of drugs during pregnancy and breastfeeding. Physicians are now supported by international recommendations released by the European League Against Rheumatism and the American College of Rheumatology, but still they must face with cultural reluctance in accepting that a pregnant woman can take medications. Patient-physician communication should be centered on the message that active maternal disease during pregnancy is detrimental to fetal health. Keeping maternal disease under control with drugs which are not harmful to the fetus is the best way to ensure the best possible outcome for both the mother and the baby. However, there might be concerns about the influence of the in utero exposure to medications on the newborn’s health conditions. Particularly, studies suggesting an increased risk of autism-spectrum-disorders in children born to women with rheumatoid arthritis has raised questions about neuropsychological impairment in the offspring of women with chronic arthritis. As a multidisciplinary group of rheumatologists and child neuropsychiatrists, we conducted a study on 16 women with chronic forms of arthritis whose diagnosis was determined before pregnancy and their 18 school-age children. The children underwent a complete neurological examination and validated tests/questionnaires. Behavioral aspects of somatization and anxiety/depression (internalizing problem) or an “adult profile” were found in nearly one third of children. Children at a high risk of neurodevelopmental problems were born to mothers with a longer history of arthritis and were breastfeed for less than 6 months of age or were not breastfeed at all. No association was found with other maternal characteristics such as autoantibody existence and disease activity during and after the pregnancy.

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“…CT is to apply X-rays or c-rays to scan a certain part of the human body together with a highly sensitive detector, which is featured with fast scanning time and clear scanned images [5]. In recent years, CT images have been extensively used in the field of medical clinical diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Machine Learning Based Image Feature Recognition and Clinical Nursing of Children’s Rheumatoid Arthritis-Related Lung Injury

2021

Scientific Programming

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This work was aimed at investigating image feature recognition and clinical nursing of children’s rheumatoid arthritis- (CRA-) related lung injury under maximum correlation minimum redundancy algorithm of machine learning. In this study, 18 children with CRA in the hospital were selected as the rheumatoid group to explore the nursing method, and 18 healthy children were selected as the control group. The maximum correlation minimum redundancy algorithm of machine learning was compared with the information gain algorithm and the Fisher score algorithm and applied in computed tomography (CT) images of 18 CRA children. The classification accuracy of the algorithm in this study (94.52%) was higher than that of the information gain algorithm (88.64%) and Fisher score algorithm (81.24%). CT alveolitis score (2.35 ± 0.72 points) of children from the rheumatoid group was markedly higher than that of the control group (1.21 ± 0.24 points) (t = 2.147 and P < 0.05 ). The nitric oxide level (14.00 ppb) of children from the rheumatoid group increased greatly compared with the control group (10.00 ppb) ( P < 0.05 ). CRA can cause a decline of lung function in children, while the nitric oxide level exhaled by children can assess the activity of RA. In addition, adopting active nursing methods can help children get better.

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Altered DNA methylation in children born to mothers with rheumatoid arthritis during pregnancy

Cited by 10 publications

References 70 publications

Tumour necrosis factor inhibitor use during pregnancy is associated with increased birth weight of rheumatoid arthritis patients’ offspring

Tumour necrosis factor inhibitor use during pregnancy is associated with increased birth weight of rheumatoid arthritis patients’ offspring

The Influence of Treatment of Inflammatory Arthritis During Pregnancy on the Long-Term Children’s Outcome

Machine Learning Based Image Feature Recognition and Clinical Nursing of Children’s Rheumatoid Arthritis-Related Lung Injury

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