Prevention and Screening for Cardiometabolic Disease Following Hypertensive Disorders in Pregnancy in Low-Resource Settings: A Systematic Review and Delphi Study

Hypertensive disorders in pregnancy (HDP) and cardiometabolic and kidney diseases are rising in low- and middle-income countries (LMICs). While HDP are risk factors for cardiometabolic and kidney diseases, cost-effective, scalable strategies for screening and prevention in women with a history of HDP are lacking. Existing guidelines and recommendations require adaptation to LMIC settings. This article aims to generate consensus-based recommendations for the prevention and screening of cardiometabolic and kidney diseases tailored for implementation in LMICs. We conducted a systematic review of guidelines and recommendations for prevention and screening strategies for cardiometabolic and chronic kidney diseases following HDP. We searched PubMed/Medline, Embase and Cochrane Library for relevant articles and guidelines published from 2010 to 2021 from both high-income countries (HICs) and LMICs. No other filters were applied. References of included articles were also assessed for eligibility. Findings were synthesized narratively. The summary of guiding recommendations was subjected to two rounds of Delphi consensus surveys with experts experienced in LMIC settings. Fifty-four articles and 9 guidelines were identified, of which 25 were included. Thirty-five clinical recommendations were synthesized from these and classified into six domains: identification of women with HDP (4 recommendations), timing of first counseling and provision of health education (2 recommendations), structure and care setting (12 recommendations), information and communication needs (5 recommendations), cardiometabolic biomarkers (8 recommendations) and biomarkers thresholds (4 recommendations). The Delphi panel reached consensus on 33 final recommendations. These recommendations for health workers in LMICs provide practical and scalable approaches for effective screening and prevention of cardiometabolic disease following HDP. Monitoring and evaluation of implementation of these recommendations provide opportunities for reducing the escalating burden of noncommunicable diseases in LMICs.

Appendix II: Delphi survey questionnaire based on the thirty-five guiding recommendations summarized from the systematic review process 1. The following pertains to standard definitions of how hypertensive disorders in pregnancy should be identified. It is important that we achieve a unified consensus in its identification for effective management. For each of the following definitions of HDP, indicate your level of agreement with each of the definition and classifications (i.e strongly disagree, disagree, neutral, agree or strongly agree)

Strongly disagree Disagree Neutral Agree Strongly agree
Identifying pregnant women with hypertensive disorders in pregnancy 1.1. As recommended by the International Society for the Study of Hypertension in Pregnancy, HDP should be classified as gestational hypertension, chronic hypertension in pregnancy and pre-eclampsia Any comment?
1.2. Chronic hypertension in pregnancy should be diagnosed as any hypertension with onset before the index pregnancy or diagnosed within the first 20 weeks of the index pregnancy Any comments?
1.3. Gestational hypertension should be diagnosed as any hypertension occurring after the first 20 weeks of pregnancy without significant proteinuria (<2++ of proteinuria on urine dipstick measurement) or any hematological or biochemical abnormality The following statements pertain to optimal setting or structure in which risk counseling services should take place for women with HDP on their risks of future cardiometabolic and kidney diseases. For each of the statements, indicate your level of agreement with the recommended setting/structure (i.e strongly disagree, disagree, neutral, agree or strongly agree) The following statements pertain to the kind of counseling information for women with HDP on their risks of future cardiometabolic and kidney diseases. For each of the statements, indicate your level of agreement with the recommended counselling information to be given to these women (i.e strongly disagree, disagree, neutral, agree or strongly agree))

All women with HDP should be informed of their increased risk of cardiometabolic and chronic kidney diseases in later life
Any comment?

4.2.
Counselling women on behavior modification should express the risk of cardio-metabolic disorders as probability scores, expressed as chances (%) of developing the disease condition Any comment? The following statements pertain to optimal timing and approach for assessing cardiometabolic risk markers in women following HDP. For each of the statements, indicate your level of agreement with the recommended timing and/or approach (i.e strongly disagree, disagree, neutral, agree or strongly agree)

5.1.
Screening for cardiometabolic risk factors should commence at between 6 -8 weeks postpartum (measurement of blood pressure, BMI and fasting blood glucose).
Any comment?

Lipid's profiling (total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides)
should not be undertaken during the 6 -weeks postpartum screening as there is substantial change at this time.
Any comment?

5.3.
If feasible, the first screening schedule at between 6 -8 weeks postpartum should be integrated with the 6 -8 weeks postpartum review by Obstetricians, Midwives, or other maternity care providers, as appropriate, for continuity of care and to enhance compliance Any comment?

5.8.
Women with hypertensive disorders in pregnancy with persistent proteinuria and/or hypertension at 6-8 weeks postpartum should be re-assessed at between 3 -6 months postpartum. Women with ongoing proteinuria, decreased estimated glomerular filtration rate (eGFR) (< 60 mL/min), or another indication of renal disease, such as abnormal urinary sediment should be referred for a nephrology review Any comment?

Target indicators of abnormal cardiometabolic markers women should be informed of?
The following statements pertain to what screening indicator(s) should be targeted and communicated in the assessment of women with HDP on their risks of future cardiometabolic and kidney diseases. For each of the statements, indicate your level of agreement with the recommended thresholds (i.e strongly disagree, disagree, neutral, agree or strongly agree) 6.1. Both the women and their caregivers should be informed that their body mass index should be maintained at ≤25kg/m 2 Any comment?

6.2.
Both the women and their caregivers should be informed that lipids profiles should maintained at < 1.7mmol/l for triglycerides and < 1.29mmol/l for high density lipoproteins cholesterol Any comment? 6.3. Both the women and their caregivers should be informed that blood pressure should be at ≤130mmHg for systolic blood pressure and ≤85mmHg for diastolic blood pressure Any comment? 6.4. Both the women and their caregivers should be informed that their fasting blood glucose should be maintained at < 5.6mmol/l or <100mg/dl

Any comment?
Appendix III: Summary of consensus for the various outcomes (i.e., in/out/no consensus).

Round on inclusion when consensus was reached Round on exclusion when consensus was reached Identifying women with HDP
As recommended by the ISSHP, HDP should be classified as Chronic hypertension in pregnancy, gestational hypertension and pre-eclampsia (round 1) Chronic hypertension in pregnancy should be diagnosed as any hypertension with onset before the index pregnancy or diagnosed within the first 20 weeks of the index pregnancy (round 2) Gestational hypertension should be diagnosed as any hypertension occurring after the first 20 weeks of pregnancy without significant proteinuria (<2++ of proteinuria on urine dipstick measurement) or any hematological or biochemical abnormality (round 2) Preeclampsia should be diagnosed as hypertension with onset after the first 20 weeks of pregnancy with significant proteinuria (≥2++ of proteinuria on urine dipstick measurement) or the presence of any hematological and biochemical abnormality (round 2) Timing of first counseling/health education Counseling on cardiometabolic risk following HDP should start early in pregnancy as this period provides a better teachable moment for adoption of healthy living (round 1) If counselling was not provided during the pregnancy, the next best opportunities should be either in the immediate postpartum period before discharge OR during the 2 weeks postpartum review (round 1)

Structure and setting of care
Counseling should be performed at facilities that women can access and by any available trained health care provider regardless of their specialties (round 1) Postpartum care counseling should be delivered within a trauma-informed model as women with post-traumatic experience are less likely to return to health facilities for regular monitoring (round 1) Where feasible, women with hypertensive disorders in pregnancy should be reviewed within a multi-disciplinary clinic involving Obstetricians/Midwives, primary care physicians, cardiologists and mental health experts to reduce inequities in health (round 1) Obstetricians, midwives, and maternity care providers should routinely counsel women with hypertensive disorders in pregnancy on their risk for cardiometabolic and kidney disorders (round 1) Where practicable, a dedicated postpartum clinic for hypertensive disorders in pregnancy be established to facilitate transition of care and to provide window of opportunities to focus on improving cardiometabolic health, primary prevention of CVD and counselling on risk factors modification (round 1) Adopt inclusion and utilization of best practice alerts in electronic medical records to facilitate risks identification and improve follow up (round 1) All maternity centers should formulate a dedicated guideline for women with hypertensive disorders in pregnancy for their continuity of care from Obstetricians/Midwives, primary care physicians or specialists as appropriate (round 1) All maternity centers should develop a comprehensive pregnancy history tool for CVD risk assessment to enable elucidation of non-traditional CVD risk factors (for example, gestational diabetic, intra-uterine growth restriction and preterm delivery) (round 1) Women with other non-traditional risk factor for cardiometabolic diseases such as gestational diabetes, intra-uterine growth restriction and preterm delivery should also be counseled and monitored postpartum (round 1) Where feasible, antenatal care card/folder/record should be modified to include section on documentation of postpartum risk assessment and monitoring of longterm risks of chronic medical conditions associated HDP and other pregnancy complications (round 1) All health care providers of maternity services should be trained on the links between hypertensive disorders in pregnancy, cardiometabolic and chronic kidney disorders (round 1) A health care provider checklist should be provided as working tool to ensure detailed and balanced communication of cardio-metabolic disease risks to patients with hypertensive disorders in pregnancy (round 1)

Counseling information needs for women identified with HDP
All women with HDP should be informed of their increased risk of cardiometabolic and chronic kidney diseases in later life (round 1)