Postpartum hypertensive disorders in the Emergency Department – A retrospective review of local practice in Calgary, Alberta

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Postpartum hypertensive disorders in the Emergency Department – A retrospective review of local practice in Calgary, Alberta Amita Mahajana, , Anne Kempb, T. Lee-Ann Hawkinsc, Amy Metcalfec,d, Shawn Dowlinge, Kara Nerenbergc,d ⁎

a

Department of Medicine – Division of Endocrinology and Metabolism, Cumming School of Medicine, University of Calgary, Canada Department of Obstetrics and Gynecology, Faculty of Medicine & Dentistry, University of Alberta, Canada c Department of Obstetrics and Gynecology, Cumming School of Medicine, University of Calgary, Canada d Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Canada e Department of Emergency Medicine, Cumming School of Medicine, University of Calgary, Canada b

ARTICLE INFO

ABSTRACT

Keywords: Postpartum hypertension Gestational hypertension Preeclampsia Emergency department Diagnosis Management

Hypertensive disorders of pregnancy (HDP) commonly occur postpartum and are associated with preventable maternal morbidity and mortality. HDP is the most common reason for presentation to the Emergency Department (ED) after delivery. However, given the broad range of non-specific symptoms, recognition and management of postpartum HDP may be delayed leading to serious adverse clinical outcomes. Objectives: To describe: (1) the clinical presentation; (2) ED physician’s diagnosis; and (3) current ED management of women with HDP in Calgary ED’s. Methods: A retrospective review of postpartum women (within 42 days of delivery) attending three Calgary EDs between 2011 and 2012 was performed. Administrative data was used to randomly select 119 women; 44 with diagnostic codes for any HDP (labeled “HDP”) and 75 with diagnostic codes for related diagnoses (e.g., abdominal pain, headache) (labeled “non-HDP”). Charts were reviewed for: maternal demographics; obstetrical history; and ED clinical findings, investigations and management. Results: Maternal characteristics were similar between groups. There was considerable overlap in clinical presentation between groups, with no significant difference for any presenting symptom. Only 52.3% (CI 40.0–64.3%) of women in the “HDP” group had HDP investigations (bloodwork and urinalysis) vs. 30.4% (CI 18.7–58.5%) of “non-HDP” (p = 0.072). HDP was diagnosed by the ED team in 42.9% (CI 31.1–55.5%) of the HDP group of whom only 40.3% (CI 28.7–53.1) received antihypertensive therapy. Conclusions: Postpartum HDP is commonly under-recognized and under-treated in the ED, highlighting opportunities for interventions to improve the recognition and management of postpartum HDP.

1. Background Hypertensive disorders of pregnancy (HDP) are serious and common pregnancy-related disorders affecting 7% of all pregnancies in Canada [1]. Worldwide, HDP are a leading cause of maternal morbidity and mortality [2,3]. A large proportion of the morbidity and mortality associated with HDP occur in the postpartum period [4,5], often due to delayed recognition and management of HDP [6,7]. Another important contributor to postpartum morbidity and mortality is a lack of routine post-discharge outpatient follow-up and screening programs for postpartum hypertension. As a result, many women with postpartum HDP present to the emergency department (ED) for care, and frequently only when symptoms of hypertension (e.g., headache, visual disturbances) ⁎

become severe [4,5,8]. Postpartum HDP refers to the persistence, exacerbation, or de novo development of gestational hypertension or preeclampsia [including eclampsia and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)] following delivery [9]. Importantly, both chronic hypertension and antepartum HDP can be exacerbated by common physiologic changes associated with the early postpartum period, including increased intravascular blood volume due to volume redistribution and catecholamine responses to pain [7,10]. Up to 30% of HDP (5–6% of preeclampsia and up to 44% of all eclamptic episodes) occur in the first six weeks postpartum [5–7]. These values are likely underestimates due to lack of standardized postpartum hypertension screening, reporting, and surveillance strategies. In the United States,

Corresponding author at: Richmond Road Diagnostic and Treatment Center, 1820 Richmond Road SW, Calgary, AB T2T5C7, Canada. E-mail address: [email protected] (A. Mahajan).

https://doi.org/10.1016/j.preghy.2019.11.009 Received 9 July 2019; Received in revised form 15 October 2019; Accepted 25 November 2019 2210-7789/ © 2019 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Please cite this article as: Amita Mahajan, et al., Pregnancy Hypertension, https://doi.org/10.1016/j.preghy.2019.11.009

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nearly one in twenty postpartum women were seen in the ED in the early postpartum period (i.e., within 42 days of delivery) and HDP were the third most common reason for ED presentation [5]. From a clinical perspective, recognition of postpartum HDP in the ED is often challenging for clinicians since it is associated with a wide range of presenting symptoms ranging from non-specific and mild symptoms (e.g., malaise) to severe symptoms (e.g., severe headache or visual disturbances), and multiple organ systems can be involved (neurological, cardiac, respiratory, gastrointestinal, etc.) [11]. Identification of postpartum HDP is further limited by a lack of patient and physician awareness of the occurrence of HDP in the postpartum period [11]. Further, there is a paucity of evidence-based protocols to guide clinicians in the management of postpartum HDP in the ED aside from general management recommendations which centre around the immediate treatment of severe hypertension (defined as systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥110 mm Hg) to reduce the risk of acute stroke (both hemorrhagic and ischemic) in women with HDP [3,7,11–17]. Given the burden of HDP in the ED and unique clinical challenges, specific information on the clinical presentation and effective management strategies of postpartum HDP in the ED is urgently needed.

symptoms at the time of clinical presentation, investigations, management, ED physician diagnosis, and clinical outcomes in the ED. The hospital charts were systematically reviewed for information relating to the recent pregnancy (antenatal records and delivery admission); postpartum HDP risk factors (i.e., history of preeclampsia or gestational hypertension [including hypertension in antepartum period or chronic hypertension], kidney disease or proteinuria at first visit, pre-pregnancy diabetes mellitus, gestational diabetes, thrombophilia, smoking, multiple pregnancy, or use of reproductive technologies) [15]; as well as fetal outcomes. Data was reviewed independently by one of two reviewers (AM and AK) who were blinded to the grouping of participants (HDP or non-HDP groups). To ensure consistency of data collection, ten charts were reviewed by both reviewers as well as a third independent reviewer (KN). 3.3. Classification of HDP in the ED The data collection forms on all participants were reviewed independently by two clinical experts in Obstetric Medicine who were blinded to the ICD-10-CA codes. Each clinical expert independently classified each participant as either HDP or non-HDP using the International Society for the Study of Hypertension in Pregnancy’s research definition of HDP [18]. Next, a consensus classification of HDP was reached between the two experts and served as the gold standard in the comparison with the ED physician’s diagnosis of HDP or non-HDP. Following this review, the patients classified by the clinical experts as women with HDP were termed “true cases” and women without HDP were termed “true controls”.

2. Objectives As a first step in addressing this important clinical gap, the objectives of this study were to describe: 1) the clinical presentation of women with postpartum HDP; 2) the Emergency Physician’s (EP) recognition of postpartum HDP; and 3) the current management of women with postpartum HDP in the ED in Calgary, Alberta, Canada.

3.4. Data analyses

3. Methods A retrospective cross-sectional study of postpartum women with HDP seen in three Calgary ED’s over the study period of January 1, 2011 to December 31, 2012 was performed. This study was approved by Conjoint Health Research Ethics Board (CHREB) at the University of Calgary (REB16-0442).

Demographic data was summarized using means with standard deviations (SD) and medians with ranges as appropriate. Comparisons between groups were made with chi-square and the Wilcoxon rank sum tests and p-values less than 0.05 were considered to be statistically significant. All analyses were conducted using Stata SE version 14, College Station, TX.

3.1. Study population

4. Results

All postpartum women who presented to three tertiary care EDs within 42 days of delivering a live or stillborn infant in Calgary, Alberta, Canada over the study period were eligible. Women with and without postpartum HDP were identified using the National Ambulatory Care Reporting System (NACRS) database. NACRS is an administrative database that includes information on all individuals who present to an ED in Alberta. A random sample size of 150 women was initially planned (i.e., 50 cases and 100 controls) to ensure a 2:1 control to case ratio for comparative analyses. However, due to incomplete records, a random sample of 119 women was identified (cases n = 44; controls n = 75), which provided roughly a 2:1 control to case ratio for comparisons. Women with HDP (i.e., hypertension, hypertensive urgency/emergency, pregnancy-induced hypertension, preeclampsia, eclampsia, and or HELLP syndrome) were defined using standard diagnostic codes for HDP [Canadian modification of the International Classification of Disease 10 (ICD-10-CA)] (Appendix A) and were classified as the “HDP group” (i.e., “cases”). Postpartum women without HDP who had related diagnostic codes (e.g., abdominal pain, headache, chest pain, etc.) (Appendix A) were classified as “non-HDP group” (i.e., “controls”).

After review of the charts on all 119 participants, 8 women were excluded from the final analysis due to incomplete patient records which limited meaningful data collection, thus 111 women were included in this study. The following results describe women in groups as classified by the expert consensus diagnosis or gold standard (i.e., “true case group” or “true control group”). Participant baseline characteristics are summarized in Table 1. On average, patients in the “true case” group (i.e., women with HDP as classified by expert consensus) were older (median age 31 vs. 29; p = 0.019) but were of similar parity. “True cases” were more likely to be diagnosed with hypertension prior to delivery (43.1% vs. 10.9%; p < 0.001), have risk factors for the development of a postpartum HDP (median number of risk factors 1 vs. 0; p = 0.015), and have used an antihypertensive agent in the recent pregnancy (24.1% vs. 5.4%; p = 0.018). There was no significant difference in the proportion of preterm deliveries between groups. The initial clinical presentation of women in the ED is summarized in Table 2. When compared to “true controls” (i.e., women without HDP as classified by expert consensus), “true cases” more frequently presented to the ED with symptoms of headache (55.4% vs. 26.1%; p = 0.002), visual disturbances (26.2% vs. 8.7%; p = 0.026) and peripheral edema (50.8% vs. 19.6%; p = 0.001). Conversely, there was no significant difference seen in other presenting symptoms including: chest pain, dyspnea, abdominal pain, anuria or a reported symptom of feeling “generally unwell”. “True cases” had significantly higher blood pressure (BP) upon presentation compared to “true controls”: median

3.2. Data extraction and management Data for all participants was extracted from the hospital and ED medical charts using a standardized data collection form. Data extracted from the ED visit included: maternal demographics, initial 2

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Table 1 Baseline participant characteristics. Clinical Variable

“True case” (HDP) N = 65

“True control” (no HDP) N = 46

p-value

Age (years) Number of postpartum HDP risk factors1

Median, Range 31, 19–46 1, 0–4

Median, Range 29.5, 18–37 0, 0–3

0.019 0.015

Primiparous HDP in most recent pregnancy Use of antihypertensive medication in recent pregnancy Preterm delivery (< 37 weeks gestation)

n, % (95% CI) 27, 41.5% (30.1–54.0) 28, 43.1% (31.5–55.5) 13, 24.1% (14.3–37.5) 12, 19.7% (11.4–31.9)

n, % (95% CI) 23, 50% (35.6–64.4) 5, 10.9% (4.5–24.0) 2, 5.4% (1.3–19.9) 4, 11.4% (4.2–2.7)

0.377 < 0.001 0.018 0.297

1 – Postpartum HDP risk factors: history of preeclampsia or gestational hypertension (including hypertension in antepartum period or chronic hypertension), kidney disease or proteinuria at first visit, pre-pregnancy diabetes mellitus, gestational diabetes, thrombophilia, smoking, multiple pregnancy, or use of reproductive technologies (15). Abbreviations: HDP = hypertensive disorder of pregnancy, n = number, CI = confidence interval.

systolic BP 145 mmHg (110–192) vs. 120 mmHg (102–142) (p < 0.001) and median diastolic BP of 90 mmHg (22–111) vs. 76 mmHg (57–92) respectively (p < 0.001). “True cases” were more likely to have abnormal findings on cardiovascular exam (cases 21.2% vs. controls 0%; p = 0.005) and respiratory exam (cases 20.8% vs. controls 2.8%; p = 0.024). There were no differences in neurological, abdominal, or peripheral edema physical exam findings between groups. Investigations are presented in Table 3. Urinalysis was completed more frequently amongst “true cases” compared to “true controls” (52.3% vs. 30.4%; p = 0.022). More HDP-related investigations [i.e., complete blood count (CBC), creatinine, uric acid, alanine transaminase (ALT), international normalized ratio (INR), and urinalysis for protein] were completed in 52.3% of “true cases” and 30.4% of the “true control” group (p = 0.072); yet there were no clinically significant differences in the results of the actual investigation. The ED clinical management of “true cases” differed significantly from “true controls”. As outlined in Table 4, 33.3% of women in the entire cohort had a consultation with a subspecialist in the ED (“true cases” 52.2% vs. “true controls” 11.9%; p < 0.001). The most

commonly requested consult service was Obstetrics and Gynecology (“true cases” 32.3% vs. “true controls” 8.7%; p = 0.005), followed by Internal Medicine (“true cases” 13.8% vs. “true controls” 0%; p = 0.010), Cardiology (“true cases” 7.7%, vs. “true controls” 0%; p = 0.075), and Neurology/Stroke (“true cases” 4.6% vs. “true controls” 0%; p = 0.265). Importantly, less than half of the original case group (i.e., women classified as having HDP using ICD-10-CA codes from NACRS) were diagnosed as having a HDP by the ED physician (42.9%; 95%CI 31.1–55.5) when compared to our gold standard consensus expert diagnosis (“true case” group). Further, only 40.3% (95%CI 28.7–53.1) of “true cases” were treated with an antihypertensive medication. Patients in both the “true cases” and “true controls” group were consistently provided with follow-up plans upon discharge (true cases 93.3% vs. true controls 90.9%; p = 0.647). 5. Discussion Overall, this study found a substantial overlap in the patient demographics, medical profile, and clinical presentation in the ED of postpartum women with or without a postpartum HDP. Importantly,

Table 2 Clinical presentation in the ED. Clinical Variable

“True case” (HDP) N = 65

“True control” (no HDP) N = 46

p-value

Main symptom at presentation Headache Visual disturbances Chest pain Dyspnea Abdominal Pain Severe edema Anuria Generally “unwell”

n, % (95% CI)

n, % (95% CI)

36, 17, 24, 24, 12, 33, 0 19,

12, 26.1% (15.3–40.9) 4, 8.7% (3.2–21.4) 17, 37.0% (24.1–51.9) 15, 32.6% (20.5–47.6) 15, 32.6% (20.5–47.6) 9, 19.6% (10.3–33.9) 1, 2.2% (0.2–14.4) 9, 19.6% (10.4–33.9)

0.002 0.026 0.997 0.639 0.087 0.001 0.414 0.248

Systolic BP on presentation (mmHg) Diastolic BP on presentation (mmHg)

(median, range) 145, 110–192 90, 22–111

(median, range) 120, 102–142 76, 57–92

< 0.001 < 0.001

Respiratory exam documented Abnormal finding Neurological exam documented Abnormal finding Abdominal exam documented Abnormal finding Peripheral edema exam documented Abnormal finding

n, % (95% CI) 53, 81.6% (70.0–89.3) 11, 20.8% (11.8–34.1) 44, 67.7% (55.2–78.1) 13, 29.5% (17.7–45.0) 51, 78.5% (66.6–86.9) 7, 13.7% (6.6–26.5) 34, 52.3% (40.0–64.3) 29, 85.3% (68.3–94.0)

n, % (95% CI) 36, 78.3% (63.8–88.0) 1, 2.8% (0.4–18.1) 22, 47.9% (33.7–62.3) 4, 18.2% (6.7–40.8) 29, 63.0% (48.1–75.9) 7, 24.0% (11.7–43.4) 14, 30.4% (18.7–45.4) 8, 57.1% (30.2–80.5)

0.670 0.024 0.036 0.384 0.074 0.239 0.022 0.058

55.4% 26.2% 36.9% 36.9% 18.5% 50.8%

(43.0–67.1) (16.8–38.4) (25.9–49.4) (25.9–49.4) (10.7–30.0) (38.6–62.9)

29.2% (19.3–41.6)

Abbreviations: BP = blood pressure, ED = emergency department; HDP = hypertensive disorder of pregnancy; n = number; CI = confidence interval. 3

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Table 3 Laboratory investigations in ED. Laboratory Investigations

True case (HDP) N = 65 n, % (95% CI)

True control (no HDP) N = 46 n, % (95% CI)

p-value

Urinalysis Proteinuria Bloodwork1 Any abnormality2 Number of HDP investigations2 0 1 2

34, 23, 58, 53,

14, 12, 35, 28,

30.4% (18.8–45.4) 85.7% (54.9–96.7) 76.1% (61.4–86.4) 80% (63.1–90.4)

0.022 0.200 0.064 0.113

1, 2.2% (0.2–14.4) 31, 67.4% (52.4–79.5) 14, 30.4% (18.7–58.5)

0.072 0.072 0.072

52.3% 67.6% 89.2% 91.4%

(40.0–64.3) (49.8–81.6) (78.9–94.9) (80.6–96.4)

1, 1.5% (0.2–10.5) 30, 46.2% (34.3–58.5) 34, 52.3% (40.0–64.3)

1. Complete blood count, creatinine, uric acid, alanine transaminase, and coagulation profile (INR). 2. Any abnormality according to normal laboratory reported range in urinalysis and bloodwork.1 n = number; CI = confidence interval.

the presence or absence of a single symptom, clinical finding, or lab result did not consistently include or exclude a diagnosis of HDP. Furthermore, the study results suggest that postpartum HDP are both under-recognized by EP’s (compared to gold standard expert consensus diagnosis) and under-treated (i.e., met criteria for postpartum HDP and were symptomatic, but not treated), with a trend towards incomplete investigations. These findings may represent potentially missed diagnosis of HDP amongst women presenting to the ED in the early postpartum period. The baseline characteristics and clinical presentation of women in the “true case” (i.e., women with postpartum HDP) and “true control” (i.e., women without postpartum HDP) groups in this study were fairly similar. However, women with postpartum HDP were older and more frequently had antepartum hypertension and additional risk factors for HDP. When compared with “true controls”, “true cases” more often presented with headaches, visual disturbances, severe peripheral edema, and higher blood pressures on initial assessment in the ED. Physical exam findings were not consistently helpful in distinguishing between women who did and did not have postpartum HDP. The ambiguity and subjective nature of interpreting physical exam findings in this patient population has been previously described [8] and is supported in the current study by the significant overlap in clinical findings between groups. These results highlight the heterogeneous clinical and biochemical findings of HDP which make the diagnosis of postpartum HDP challenging, particularly when index of suspicion for the disorder may be low [7,9,13,14]. One of the most notable findings of the current study was the trend towards incomplete or partial investigations for HDP in the ED of all postpartum women. Both groups of women had incomplete standard investigations assessing end-organ involvement from HDP (i.e.,

urinalysis for proteinuria, CBC, creatinine, uric acid, ALT, etc.). Only 52.3% of “true cases” and 30.4% of “true controls” (p-value = 0.072) had both urinalysis and HDP bloodwork ordered in the ED. This suggests a potential lack of HDP awareness of the role of these investigations in the postpartum period, which may result in missed detection of postpartum HDP in the ED. This is important as approximately 20–30% of women with HELLP syndrome develop laboratory abnormalities > 48 h after delivery [9], up to 44% of all eclamptic seizures occur in the postpartum period [9,13,14], and these conditions may be identified early through the use of routine laboratory investigations. Further use of magnesium sulphate has been demonstrated to reduce the risk of seizure (i.e., eclampsia) in women with HDP, even in the postpartum period [19]. Moreover, as the length of stay after delivery continues to decrease, many women at risk of HDP will be out-patients when symptoms of HDP develop and subsequently present to the ED for initial diagnosis and management [20]. Another important finding of this study is the under-recognition of postpartum HDP by EP’s. Compared with the study’s gold standard (i.e., consensus classification between two clinical experts) only 42.9% of the women classified as “true cases” of HDP were diagnosed by the ED physicians as having HDP and only 40.3% of the “true cases” of HDP received antihypertensive therapy in the ED. This discrepancy in diagnosis is clinically important and may lead to delays in recognition and treatment of postpartum HDP as evidenced by the limited use of antihypertensive therapy. These findings may reflect a lack of awareness of the importance of aggressive and immediate BP lowering in the postpartum period to reduce the risks of hemorrhagic and ischemic stroke [3,11]. Studies examining postpartum HDP have demonstrated findings consistent with the above results, suggesting that postpartum HDP are

Table 4 Management in ED. True case (HDP) N = 65

True control (no HDP) N = 46

p-value

Consultations Any consult Internal Medicine Obstetrics & Gynecology Neurology/Stroke Cardiology Obstetric Medicine Nephrology

(n, %, 95% CI)

(n, %, 95% CI)

32, 49.2% (37.1–61.4) 9, 13.8% (7.3–24.8) 21, 32.3% (21.9–44.8) 3, 4.6% (1.5–13.6) 5, 7.7% (3.2–7.4) 0 0

5, 10.9% (4.5–26.0) 0 4, 8.7% (3.2–21.4) 0 0 0 0

< 0.001 0.010 0.005 0.265 0.075

Any antihypertensive used in ED or for home after discharge1 Any follow-up plan provided

25, 40.3% (28.7–53.1) 56, 93.3% (83.3–97.5)

0, 0% 40, 90.9% (77.7–96.6)

< 0.001 0.647

From any drug class – e.g., labetalol, hydralazine, nifedipine etc. 4

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clinically heterogeneous [9] making accurate diagnosis and prompt treatment challenging. Yancey et al. also found there were no universal, disease-specific, presenting symptoms or signs to identify preeclampsia amongst 22 women who presented to the ED with postpartum preeclampsia [8]. Similarly, a recent study found no consistent clinical predictors for postpartum eclampsia [6]. Interestingly, several authors report women may present with a de-novo postpartum HDP without evidence of HDP in the antenatal or peripartum period [5,7,8,14], with the highest rate of eclampsia seen in patients without an antenatal diagnosis of HDP [4]. It is hypothesized, this increased risk of eclampsia may be partly due to lack of healthcare provider and patient knowledge that the risk of HDP persists into the postpartum period, even without a previous antenatal diagnosis [5,7,10]. In a multicentre study done by Chames et al., 91% of women with postpartum preeclampsia reported at least one non-specific symptom (i.e., headache, abdominal pain, blurry vision etc.), but only 33% sought medical care for these symptoms, suggesting that education needs to target both healthcare providers and postpartum women [4]. Thus targeted knowledge dissemination strategies educating ED healthcare providers about postpartum HDP may be an ideal strategy as early postpartum women are frequently evaluated in the ED [10]. This study has notable strengths. First, the study findings are generalizable to other Canadian centres due to the use of three tertiary care EDs from a single Canadian city that serves a wide range of patient demographics and ethnicities and the use of an inclusive eligibility criteria. Additionally, these findings are broadly applicable to countries outside of Canada, given a similar lack of specific national clinical practice guideline recommendations for management of postpartum hypertension in the ED [12,16,21]. A second strength was the comprehensive collection of clinical variables through detailed chart review which supplemented the basic administrative data. These strengths, however, must be taken into consideration along with the study’s limitations which include the relatively small sample size of 111 women, and the cross-sectional study design. To mitigate the bias associated with the small sample size, we intentionally used a ratio of approximately 2:1 cases:controls. The study design, (i.e., reliance on ED physician charting of findings) may have limited collection of clinically relevant variables, and therefore the study’s findings may underestimate the associations of specific clinical variables with the diagnosis of HDP, however, this ought not impact the main finding of underclassification and under-treatment of HDP in the postpartum period.

management of postpartum HDP in the ED. Future steps include the development, implementation and evaluation of a clinical practice management protocol for postpartum HDP in the ED and determine whether use of a postpartum HDP management protocol impacts clinically important maternal outcomes. Acknowledgements None. Funding support A. Kemp was supported by a studentship from Emergency Strategic Clinical Network. A. Metcalfe is supported by a New Investigator Award from the Canadian Institutes of Health Research (CIHR). K. Nerenberg was supported by a New Investigator Award from the Heart and Stroke Foundation (HSF) as well as the Women’s Heart and Brain Health Research Chair from the HSF and CIHR. Declarations of interest None. Author contributions A. Mahajan: I declare I participated in the study design, data collection, and final manuscript writing and that I have seen and approved the final version. I have no conflicts of interest. A. Kemp: I declare I participated in the data collection and that I have seen and approved the final version. I have no conflicts of interest. A. Metcalfe: I declare I participated in the study design, data analysis, and manuscript editing and that I have seen and approved the final version. I have no conflicts of interest. T.L. Hawkins: I declare I participated in the study design and manuscript editing and that I have seen and approved the final version. I have no conflicts of interest. S. Dowling: I declare I participated in the study design and manuscript editing and that I have seen and approved the final version. I have no conflicts of interest. K. Nerenberg: I declare I participated in the study design and final manuscript editing and review, and that I have seen and approved the final version. I have no conflicts of interest.

6. Conclusion/future steps This study identified important clinical gaps in the recognition and Appendix A

Table A1 ICD-10-CA codes used to classify patients as cases (women with HDP) and controls (women without HDP) [22]. ICD-10-CA Code

Case Definitions

ICD-10-CA Code

Control Definitions

I10.x I11.x I12.x I13.x I15.x I42.x I50.x J81.x N17.x O10.x

Essential (primary) hypertension Hypertensive heart disease Hypertensive renal disease Hypertensive heart and renal disease Secondary hypertension Cardiomyopathy Heart failure Pulmonary oedema Acute Renal Failure Pre-existing hypertension complicating pregnancy, childbirth and the puerperium Pre-existing hypertensive disorder with superimposed proteinuria

D64.8 D64.9 D69.3 F05.x G43.x G44.x G45.x H53.x H57.1 H81.3

Other specified anaemias Anaemia, unspecified Idiopathic thrombocytopenic purpura Delirium, not induced by alcohol and other psychoactive substances Migraine Other headache syndromes Transient cerebral ischaemic attacks and related syndromes Visual disturbances Ocular pain Other peripheral vertigo

H81.4

Vertigo of central origin

O11.x

(continued on next page) 5

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Table A1 (continued) ICD-10-CA Code

Case Definitions

ICD-10-CA Code

Control Definitions

O12.x

Gestational [pregnancy-induced] oedema and proteinuria without hypertension Gestational [pregnancy-induced] hypertension without significant proteinuria Gestational [pregnancy-induced] hypertension with significant proteinuria Eclampsia Unspecified maternal hypertension Cardiomyopathy in the puerperium Postpartum acute renal failure Migraine Other headache syndromes Spinal and epidural anaesthesia-induced headache during pregnancy Spinal and epidural anaesthesia-induced headache during labour and delivery Spinal and epidural anaesthesia-induced headache during the puerperium Headache

I46.x

Cardiac arrest

I48.x

Atrial fibrillation and flutter

I49.x

Other cardiac arrhythmias

I51.4 I64.x N10.x N11.x N12.x N15.x O26.9

Myocarditis, unspecified Stroke, not specified as haemorrhage or infarction Acute tubulo-interstitial nephritis Chronic tubulo-interstitial nephritis Tubulo-interstitial nephritis, not specified as acute or chronic Other renal tubulo-interstitial diseases Pregnancy-related condition, unspecified

O29.4

Spinal and epidural anaesthesia-induced headache during pregnancy

O74.5

Spinal and epidural anaesthesia-induced headache during labour and delivery Spinal and epidural anaesthesia-induced headache during the puerperium Anaemia complicating pregnancy, childbirth and the puerperium Diseases of the circulatory system complicating pregnancy, childbirth and the puerperium Diseases of the respiratory system complicating pregnancy, childbirth and the puerperium Abnormalities of heart beat Elevated blood-pressure reading, without diagnosis of hypertension Precordial pain Other chest pain Chest pain, unspecified Disorientation, unspecified Other and unspecified symptoms and signs involving cognitive functions and awareness Dizziness and giddiness Headache Malaise and fatigue Syncope and collapse Convulsions, not elsewhere classified Oedema, not elsewhere classified

O13.x O14.x O15.x O16.x O90.3 O90.4 G43.x G44.x O29.4 O74.5 O89.4 R51.x

O89.4 O99.0 O99.4 O99.5 R00.x R03.0 R07.2 R07.3 R07.4 R41.0 R41.8 R42.x R51.x R53.x R55.x R56.x R60.x

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