Background
Chronic Kidney Disease (CKD) is an under-recognised, serious and increasing major health problem, which disproportionately affects Indigenous peoples and lower socioeconomic groups [
1‐
3] . The prevalence of CKD amongst Australian mothers is rising due to the population rise in diabetes, obesity and older age in pregnancy [
4]. Over 5% of Australian women of child-bearing age have albuminuria or abnormal estimated GFR (eGFR) indicating CKD [
2]. In Australia in 2016, 25% of all women with a functioning renal transplant and 51% of all female incident end-stage kidney disease (ESKD) cases were in women of reproductive age (15–44 years) [
5]. Parenthood is a major concern for women with CKD, and women experience important fears and uncertainties about risks to their own and their baby’s health [
6,
7]. Women of childbearing age with CKD may face difficult decisions about parenthood while experiencing significant comorbidity and impairment to activities of daily living. Navigating paths to parenthood via complex shared decision-making can be challenging and accurate outcome data would enable evidence-based risk stratification [
7].
There is a knowledge gap regarding the burden of CKD in pregnancy in the Australian context. Determining the prevalence of kidney disease in pregnancy has not been easy, due to varying definitions, changing staging systems and poor capture of renal markers (serum creatinine and urine protein) in pregnancy cohorts [
8,
9]. The Australia and New Zealand dialysis and transplant registry (ANZDATA) reports pregnancy rates for chronic dialysis and transplant recipients of 3.3/1000 person-years and 20/1000 person-years respectively but is likely under-reported [
10‐
12]. Rates of advanced stage CKD (Stage 3b-4), and non-chronic Acute Kidney Injury (AKI) occurring in pregnancy in Australia are unknown. This information is important when developing maternity and renal services.
There is currently no data on how significant kidney disease in pregnancy (CKD stage 3b-5, dialysis, transplant or AKI) impacts upon pregnancy care and how it is managed in Australia. Registry and perinatal datasets currently active in Australia collect some data items and past analyses of the ANZDATA registry have provided some information on pregnancy rates and basic pregnancy outcomes [
10,
13]. However, these provide minimal insights into obstetric and perinatal adverse events, therapy and interventions required during pregnancy, models of care delivered, and utilisation of health care resources including hospitalisation and other events.
This knowledge is important to obtain as pregnancy in women with CKD is associated with worse obstetric and perinatal outcomes including preterm birth, small for gestational age, and pre-eclampsia and gestational hypertension [
14,
15]. The risk is increased, even in women with Stage 1 CKD [
16,
17] and continues to rise as CKD stage advances [
15,
18,
19]. Pre-conception eGFR< 40 ml/min, poorly controlled hypertension and proteinuria are factors associated with higher rates of obstetric and perinatal complications [
20‐
23]. As pre-conception renal function worsens, the risk of “stage shift” or deterioration in renal function also increases, and may necessitate dialysis during pregnancy [
9,
24,
25].
Pregnancies in women receiving chronic dialysis are rare due to the reduced fertility of women with advanced kidney failure, and are particularly challenging in terms of maternal care [
8]. The recognition that intensive dialysis improves outcomes has led to changes in clinical practice and counselling for women with advanced CKD [
19,
24,
26,
27]. Australian women receiving chronic dialysis have a 27% fetal loss rate compared with 7% among all pregnancies [
10]. Among live births, 75% are preterm and more than 50% of such babies have birth weights less than the 10th centile [
10]. Outcomes are better for women who commence dialysis after conception compared with those who conceive while receiving chronic dialysis [
10,
28]. Even after successful kidney transplantation, these pregnancies continue to have high rates of pre-eclampsia (> 25%), prematurity and poor fetal growth (> 50%) [
12,
13,
29]. Worse graft function (serum creatinine > 110 μmol/L) during pregnancy can predict risk of pre-eclampsia and kidney function trajectory including significantly higher rates of graft loss within 3 years of giving birth [
29].
The incidence of Acute Kidney Injury (AKI) in pregnancy has decreased in recent years in developed countries, mainly due to improvement in peripartum sepsis care [
30]. However, AKI still represents a potentially catastrophic event in pregnancy, caused predominantly by pre-eclampsia [
31]. There is also enhanced awareness and understanding of newer conditions such as atypical haemolytic uraemic syndrome [
32]. AKI in one pregnancy is associated with worse outcomes in the next [
33]. Approximately 1/10,000 pregnancies are complicated by AKI that requires dialysis, which was associated with poor perinatal outcomes and increased maternal death rate in one Canadian study [
34]. There are no Australian data regarding frequency, causes and outcomes of pregnancy-related AKI, and this remains an important area to investigate.
Severe CKD and AKI in pregnancy, while uncommon, cause a high burden of maternal and perinatal morbidity [
14,
15,
34]. A lack of information regarding outcomes for women with these conditions in Australia including the maternal mortality and morbidity, model of care, perinatal outcomes, and access to services, presently limits the health service providers’ ability to counsel and manage affected women. The model of care required for such high risk pregnancies may not be equitably available to all women at higher risk, particularly those who are Indigenous, geographically isolated, from a lower socioeconomic status (SES) or from a culturally and linguistically diverse (CALD) group.
The aim of this study is to determine the Australian prevalence, pregnancy-related and pre-existing maternal and renal morbidity and perinatal outcomes associated with serious maternal kidney disease in pregnancy; and to describe patterns of presentation, pregnancy management and models of care and adequacy of healthcare delivery in these pregnancies. We will achieve this by development of a new framework for capture of maternal and fetal outcomes for cases of significant kidney disease in pregnancy, using the existing Australasian Maternity Outcomes Surveillance System (AMOSS) research platform which is embedded in many maternity units across Australia. We hypothesise that mothers with CKD and AKI will have a substantial pregnancy related and pre-existing medical morbidity, and that babies born to these mothers will have higher prematurity and consequent perinatal morbidity. Adverse outcomes may be related to modifiable factors in pre-pregnancy and antenatal care, including access to specialised services, improved blood pressure management and dialysis treatment, fetal surveillance and timing of delivery. The study findings will inform a guideline and policy development and improve counselling for this high risk cohort.
Discussion
This AMOSS study will highlight the issue of serious kidney disease in pregnancy in Australia, with heightened awareness in approximately 260 maternity units and among obstetric and renal healthcare providers across the country. The study will focus on cases of serious kidney disease in pregnancy that, while uncommon, can cause significant morbidity for mothers and babies, present clinical complexity for clinicians, and place a disproportionate burden on health care resources. The study will fill an important knowledge gap on the prevalence and models of care for this high-risk cohort of women.
The strengths of this study come from the AMOSS research model, which encompasses 96% of hospital births in Australia, and where cases can be identified prospectively and data collected after birth. In addition, multiple sources to identify eligible participants will increase the ability to capture cases, thereby minimising missed cases. The main challenge in this study will be the data collection for women who (1) receive their obstetric and renal care at different locations, or (2) receive renal care at a non-AMOSS site. To overcome these challenges, ethics approval was granted at most sites for the AMOSS Project Coordinator to receive minimal identifying details of prospective patients receiving renal care at one site and pass those details on to the onsite AMOSS data collector at the woman’s maternity hospital. For women receiving renal care at a non-AMOSS site, separate ethical and/or governance approval for data collection at the specialist clinic and matching with maternity data will be sought on a case-by-case basis.
The results of this study will be immediately relevant and enable translation into clinical practice. Specifically, we will.
a)
Improve the evidence base for pre-pregnancy counselling and pregnancy management, and will promote this as an important pathway towards improved outcomes. We will identify healthcare professional groups to target for strategic education in specialist and primary care, and mechanisms to target high-risk women antenatally. Previous AMOSS studies have led to important improvements in safety and quality of care for pregnant women suffering from rare and under-studied conditions, where there is often a lack of data and clinical experience to guide management.
b)
Promote clinical guideline and policy development in Australia by providing an evidence base describing current models of care, and highlighting gaps in care or risk factors for adverse outcomes. Currently, there are no Australian guidelines or policies to facilitate delivery of specialised pregnancy care to women with renal disease.
c)
Disseminate our findings to key stakeholders (clinical providers - medical, midwifery, nursing, allied health, government policy planners and patient/consumer groups) involved in the care of women with CKD and AKI, women with high-risk pregnancy, their babies and their families. We will develop resources for health providers and patients through engagement with renal and pregnancy consumer organisations.
d)
Use this study to form the foundation for developing new systems for ongoing data capture regarding maternal kidney disease, including the potential to re-purpose the data collection instrument into an ongoing registry.
Given that no other studies have explored serious maternal kidney disease in the Australian birth cohort, we anticipate the results will be of great interest to the obstetric and renal community nationally and internationally.
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