The four Ds—the four things that matter most to ensure rheumatic disease control in pregnancy and beyond
Year: 2025
Type: editorial
Abstract: This editorial refers to ‘Beyond pregnancy in systemic autoimmune diseases: a focus on postpartum experience from a referral centre’ by Dina Zucchi et al., 2025; https://doi.org/10.1093/rheumatology/keaf371. In the book, ‘The four things that matter most’, Dr Ira Bycock describes four phrases that can be entwined into daily life to transform relationships at all stages of life. We propose a different quadruplet of words using an alliteration of Ds—Discuss, Disease, Damage, and Drugs—to frame pregnancy planning consultations and transform the reproductive journey of people with inflammatory rheumatic diseases (IRD). This journal issue includes a study of postpartum outcomes among individuals with IRD by Zucchi and colleagues that will further inform pregnancy planning consultations [1]. Their single-centre, prospective study, conducted over 24 years, describes a high rate of adverse outcomes postpartum. Importantly, active disease in pregnancy was the strongest predictor of postpartum flare. Their findings highlight the importance of disease control to improve outcomes during pregnancy and beyond. There is a rising prevalence of autoimmune diseases in pregnancy, including IRDs such as RA and SLE [2]. Given the predilection of these diseases for females of reproductive age, an appreciable number may be considering and achieving pregnancy. In the UK, based on population figures [3] and prevalence data in females with RA aged 25–45 years [4] and SLE aged 20–49 years [5] there are ∼25 000 females with these conditions who may plan or become pregnant. Information and guidance relating to the management of IRDs in pregnancy and breastfeeding has increased dramatically over the course of the study by Zucchi and colleagues, with increasing recommendations relating to the prescribing of conventional and biologic DMARDs in pregnancy and breastfeeding, including British Society for Rheumatology (BSR) guidelines [6]. The use of these drugs in treat-to-target regimes outside of pregnancy, particularly in RA, has enabled substantial improvements in disease control, resulting in more people considering pregnancy [7]. Although attitudes and treatment paradigms in pregnancy have changed appreciably over the time period of the Zucchi and colleagues’ study, IRDs remain associated with an increased burden of adverse pregnancy outcomes, particularly with active disease, so pregnancy planning for people with IRD is vital [8]. We propose a simple framework—the four Ds—to guide consultations between healthcare professionals and people with IRD. The four Ds are: Discuss, to ask and thus talk about the issues; Disease features, such as diagnosis, autoantibody profile and activity, as all can influence pregnancy management; Damage, to consider the presence, severity and impact of disease related damage and Drugs, which must be reviewed to make sure that disease control is achieved on medications that are compatible with pregnancy (Table 1). Main topics for consideration within the framework of the ‘four Ds’ Pregnancy planning or avoidance Timing of pregnancy Importance of breastfeeding Diagnosis and autoantibody profile Ensure disease control before and during pregnancy Risk of flare in pregnancy and postpartum Presence/degree of organ dysfunction Impact on pregnancy Impact of pregnancy on damage progression Continue compatible and stop harmful drugs Consider the risk/balance of newer drugs Advice on use in lactation Pregnancy planning or avoidance Timing of pregnancy Importance of breastfeeding Diagnosis and autoantibody profile Ensure disease control before and during pregnancy Risk of flare in pregnancy and postpartum Presence/degree of organ dysfunction Impact on pregnancy Impact of pregnancy on damage progression Continue compatible and stop harmful drugs Consider the risk/balance of newer drugs Advice on use in lactation Main topics for consideration within the framework of the ‘four Ds’ Pregnancy planning or avoidance Timing of pregnancy Importance of breastfeeding Diagnosis and autoantibody profile Ensure disease control before and during pregnancy Risk of flare in pregnancy and postpartum Presence/degree of organ dysfunction Impact on pregnancy Impact of pregnancy on damage progression Continue compatible and stop harmful drugs Consider the risk/balance of newer drugs Advice on use in lactation Pregnancy planning or avoidance Timing of pregnancy Importance of breastfeeding Diagnosis and autoantibody profile Ensure disease control before and during pregnancy Risk of flare in pregnancy and postpartum Presence/degree of organ dysfunction Impact on pregnancy Impact of pregnancy on damage progression Continue compatible and stop harmful drugs Consider the risk/balance of newer drugs Advice on use in lactation Discuss highlights the importance of having pregnancy planning conversations as they are often overlooked in time-limited consultations. Worldwide, a lack of knowledge about sex and pregnancy, and contraceptive failure or non-use, contributes to an unintended pregnancy rate of 45%. Lack of pregnancy planning in people with IRD is associated with an increased incidence of adverse pregnancy outcomes [9], and restrictions on reproductive rights mean that not all females can access abortion services, despite the potential adverse socioeconomic and health consequences of unplanned pregnancy [10]. Therefore, early and regular family planning conversations led by rheumatology healthcare professionals are vital to optimize maternal and infant outcomes [11]. Disease considerations include diagnosis, autoantibody profile and activity. Diagnosis is relevant since the risk of adverse pregnancy outcomes is increased in SLE and other IRD with internal organ involvement, compared with inflammatory arthritis. The presence of certain autoantibodies, principally anti-Ro and antiphospholipid antibodies, has implications for modifications of treatment and monitoring of IRD in pregnancy [8]. Increased disease activity is associated with an increased risk of adverse pregnancy outcomes: pre-term delivery, preterm birth and small for gestational age, and pre-eclampsia in RA and SLE pregnancies [7, 8]. Therefore, the presence of active disease should trigger advice to delay conception until a period of disease quiescence on pregnancy-compatible medication has been achieved. Damage related to significant organ dysfunction due to any IRD greatly increases the prospect of maternal and/or fetal morbidity/mortality. Renal dysfunction due to SLE and chronic kidney disease (CKD) of various aetiologies is associated with increased risks of adverse maternal and fetal outcomes, and people with advanced CKD before pregnancy have an increased risk of accelerated decline in renal function during or shortly after pregnancy [8]. Specific conditions, including pulmonary hypertension, severe interstitial lung disease or advanced heart failure, are associated with particularly high rates of maternal and fetal mortality [8]. In general, pregnancy is considered ‘contraindicated’ in these settings, and should prompt advice to avoid pregnancy, access reliable contraception, and, if available, dedicated pre-pregnancy counselling from a physician with expertise in maternal medicine. Drug therapy must be maintained to ensure suppression to no/low levels of disease activity and reduce the increased risk of adverse outcomes with poorly controlled (moderate/high levels of) disease activity before, during and after pregnancy. Information supporting increasing use of biological DMARDs to control disease, plus guidance on whether/when to stop them before or during pregnancy, is now available [6]. Medication alterations before, during and after pregnancy are often required to maintain disease control with medications that are compatible with pregnancy and lactation, with avoidance of teratogenic drugs. These discussions should take place before conception, particularly in those with active disease, damage related to disease or on teratogenic medication, and then continue through pregnancy and postpartum to minimize the risk of adverse pregnancy outcomes. The study by Zucchi and colleagues highlights the risks of the postpartum period, and chimes with findings from maternal surveillance in the general population, showing that 70% of maternal deaths occur in the first 6 weeks postpartum, compared with 30% in pregnancy itself (MBBRACE-UK). We propose a simple framework to discuss important issues in relation to the management of IRD in pregnancy. These four Ds—Discuss, Disease, Damage and Drugs—really do matter most when guiding healthcare professionals to have these vital conversations to optimize the pregnancy journey of people with IRDs. No new data were generated or analysed in support of this article. No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this manuscript. Disclosure statement: I.G. has received unrestricted research grants from Union Chimique Belge (UCB), honoraria from MGP as a coauthor on an educational review article in 2020 and speaker fees from UCB and has participated in advisory boards for UCB. B.G. has received speaker fees from GSK. B.G. is supported by Vs Arthritis (grant number 22975).
Source: Lara D. Veeken
Authors: Bethan Goulden, Ian Giles
Institution: University College London
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: UCB, Union Chimique Belge
OpenAlex ID: W4413140894