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Challenging the definition of hypertension in pregnancy: a retrospective cohort study

Published:January 16, 2020DOI:https://doi.org/10.1016/j.ajog.2019.12.272

      Background

      In routine antenatal care, blood pressure is used as a screening tool for preeclampsia and its associated adverse outcomes. As such women with a blood pressure greater than 140/90 mm Hg undergo further investigation and closer follow-up, whereas those with lower blood pressures receive no additional care. In the nonpregnant setting, the American College of Cardiology now endorses lower hypertensive thresholds and it remains unclear whether these lower thresholds should also be considered in pregnancy.

      Objective

      (1) To examine the association between lower blood pressure thresholds (as per the American College of Cardiology guidelines) and pregnancy outcomes and (2) to determine whether there is a continuous relationship between blood pressure and pregnancy outcomes and identify the point of a change at which blood pressure is associated with an increased risk of such outcomes.

      Study Design

      This was a retrospective study of singleton pregnancies at Monash Health, Australia. Data were obtained with regards to maternal characteristics and blood pressure measurements at varying gestational ages. Blood pressures were then categorized as (1) mean arterial pressure and (2) normal, elevated, stage 1 and stage 2 hypertension, as per the American College of Cardiology guidelines. Multivariable regression analysis was performed to identify associations between blood pressure categories and pregnancy outcomes.

      Results

      This study included 18,243 singleton pregnancies. We demonstrated a positive dose–response relationship between mean arterial pressure and the development of preeclampsia in later pregnancy. Across all gestational ages, the risk of preeclampsia was greater in those with “elevated blood pressure” and “stage 1 hypertension” in comparison with the normotensive group (adjusted risk ratio; 2.45, 95% confidence interval, 1.74–3.44 and adjusted risk ratio, 6.60; 95% confidence interval, 4.98–8.73 respectively, at 34–36 weeks’ gestation). There was also an association between stage 1 hypertension, preterm birth, and adverse perinatal outcomes.

      Conclusion

      This study demonstrated that preeclampsia and the associated adverse outcomes are not exclusive to those with blood pressures greater than 140/90 mm Hg. As such, those with prehypertensive blood pressures may also benefit from closer monitoring. Further research is essential to determine whether lowering the blood pressure threshold in pregnancy would improve detection and outcomes.

      Key words

      Hypertension in pregnancy is defined as a systolic blood pressure (SBP) greater than or equal to 140 mm Hg, or a diastolic blood pressure (DBP) greater than or equal to 90 mm Hg on 2 occasions, at least 4 hours apart.
      • Tranquilli A.L.
      • Dekker G.
      • Magee L.
      • et al.
      The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP.
      • Lowe S.A.
      • Bowyer L.
      • Lust K.
      • et al.
      SOMANZ guidelines for the management of hypertensive disorders of pregnancy 2014.
      ACOG Practice Bulletin No
      202: Gestational Hypertension and Preeclampsia.
      • Visintin C.
      • Mugglestone M.A.
      • Almerie M.Q.
      • et al.
      Management of hypertensive disorders during pregnancy: summary of NICE guidance.
      This definition is derived from hypertensive guidelines in nonpregnant individuals and is currently used as a screening tool for preeclampsia (PE) and a prognostic marker for adverse pregnancy outcomes. As a result, women with a blood pressure (BP) greater than 140/90 mm Hg receive increased monitoring with additional antenatal reviews, regular testing for proteinuria and biochemical derangements of PE, and ultrasound scans to assess fetal growth and wellbeing.
      • Lowe S.A.
      • Bowyer L.
      • Lust K.
      • et al.
      SOMANZ guidelines for the management of hypertensive disorders of pregnancy 2014.
      ACOG Practice Bulletin No
      202: Gestational Hypertension and Preeclampsia.
      • Visintin C.
      • Mugglestone M.A.
      • Almerie M.Q.
      • et al.
      Management of hypertensive disorders during pregnancy: summary of NICE guidance.

      Why was the study conducted?

      In current practice, women with a blood pressure greater than 140/90 mm Hg undergo further investigation for preeclampsia and the associated pregnancy complications. Recently, the American College of Cardiology has endorsed lower blood pressure thresholds for the diagnosis of hypertension, and it remains unclear whether these should be used in pregnancy. This study was conducted to determine the association between lower blood pressure thresholds, preeclampsia, and adverse outcomes.

      Key findings

      Women with stage 1 hypertension have an increased risk of preeclampsia, preterm birth, and adverse perinatal outcomes in comparison with the normotensive group. There is also a dose–response relationship between blood pressure and preeclampsia, and this is significant at a mean arterial pressure of 85–95 mm Hg.

      What does the study add to what is known?

      There is a dose–response relationship between blood pressure and preeclampsia and the associated adverse outcomes are not exclusive to those with blood pressures greater than 140/90 mm Hg.
      In the nonpregnant population, there has been a change in the definition of hypertension itself. In 2017, the American College of Cardiology (ACC) endorsed lower thresholds for hypertension such that (1) “elevated blood pressure” is a SBP of 120–129 mm Hg and DBP <80 mm Hg, (2) “stage 1 hypertension” is a SBP of 130–139 mm Hg or DBP of 80–89 mm Hg, and (3) “stage 2 hypertension” is a SBP ≥140 mm Hg or a DBP ≥90 mm Hg.
      • Whelton P.K.
      • Carey R.M.
      • Aronow W.S.
      • et al.
      2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
      These changes have been informed by evidence that targeting lower BPs may reduce the risk of long-term cardiovascular morbidity.
      • Reboussin D.M.
      • Allen N.B.
      • Griswold M.E.
      • et al.
      Systematic Review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
      ,
      • Wright Jr., J.T.
      • Williamson J.D.
      • et al.
      SPRINT Research Group
      A randomized trial of intensive versus standard blood-pressure control.
      However, the ACC guidelines do not comment on whether these thresholds should be adopted in pregnancy, and there is little research in this field. The few studies that have addressed this question support the use of lower BP thresholds, as this likely promotes earlier diagnosis of PE.
      • Hu J.
      • Li Y.
      • Zhang B.
      • et al.
      Impact of the 2017 ACC/AHA guideline for high blood pressure on evaluating gestational hypertension-associated risks for newborns and mothers.
      • Sutton E.F.
      • Hauspurg A.
      • Caritis S.N.
      • Powers R.W.
      • Catov J.M.
      Maternal outcomes associated with lower range stage 1 hypertension.
      • Hauspurg A.
      • Parry S.
      • Mercer B.M.
      • et al.
      Blood pressure trajectory and category and risk of hypertensive disorders of pregnancy in nulliparous women.
      However, most do not examine the impact of lower thresholds on other clinically relevant adverse outcomes such as preterm birth, fetal growth restriction, and perinatal morbidity and mortality. Furthermore, few studies have determined whether there is an optimal threshold for the definition of hypertension in pregnancy.
      This study aims to examine the relationship between BP and adverse pregnancy outcomes. To explore this, we will first examine BP as categorized by the ACC criteria. Using mean arterial pressure (MAP), we will then examine the relationship between BP and pregnancy outcomes as a continuum. With the latter, we aim to identify a point of change at which MAP correlates with PE and adverse pregnancy outcomes.

      Material and Methods

      We conducted a retrospective cohort study and examined medical records of all births at Monash Health between January 1, 2016, and July 31, 2018. Monash Health is a metropolitan university hospital network in Melbourne, Australia, that provides care for approximately 9000 pregnant women per year across 2 secondary obstetric units and 1 tertiary referral obstetric unit. All centers are governed by the same policies, procedures, and guidelines. Multiple pregnancies and pregnancies complicated by major fetal abnormalities were excluded. We also excluded pregnancies where no BP measurements were available in at least one of the prespecified gestational ages. This study was granted exemption from ethics review by Monash Health Human Research Ethics Committee (ID RES-18-0000-664Q). The data that support the findings of this study are available from the corresponding author upon reasonable request.

      Data extraction

      Data were extracted from the Birthing Outcomes System (Melbourne Clinical and Translational Sciences [MCATS], Melbourne, Australia), an electronic database used to record antenatal, intrapartum, and postpartum information pertaining to pregnancy care. Within the hospital network, clinicians complete 46 prespecified fields in the Birthing Outcomes System database throughout pregnancy. Data also were supplemented through electronic medical records, pathology, and I.Patient Manager database (IPM, Sydney, Australia). The variables extracted are listed in Supplemental Table 1 and can be divided into maternal and pregnancy characteristics, medical and obstetric history, BP measurements, and pregnancy outcomes.
      During pregnancy, BP measurements at Monash Health are performed by trained midwifery and medical staff using a sphygmomanometer. BP is measured with women in a seated position, using an appropriately sized cuff for arm circumference. SBP is recorded when Korotkoff I is auscultated and DBP is recorded at Korotkoff V. The first measurement available within the prespecified gestational ages of less than 20 weeks, 20–24 weeks, 28–32 weeks, and 34–36 weeks was extracted for this study. These gestations were chosen for several reasons. First, they encompass points of hemodynamic change in pregnancy including the nadir of BP at 20–24 weeks of gestation. Second, assessment at early gestational ages will provide insight into whether those with prehypertensive BPs at the booking visit are at a greater risk of adverse outcomes. This population may then benefit from being stratified as high risk and receiving closer monitoring and aspirin prophylaxis. We also chose to evaluate BP in later pregnancy, as in the late second and third trimesters the decision to further investigate for PE is determined by a BP ≥140/90 mm Hg. In this population, we aimed to determine whether those with BPs lower than this threshold are also at increased risk and therefore may benefit from earlier evaluation and closer monitoring. Lastly, hospital guidelines require that women receive routine antenatal review at these gestational ages. Thus, these gestations enabled maximization of the number of data points available for analysis.

      Outcomes

      All maternal and perinatal complications were confirmed through manual assessment of medical records and pathology data. The outcomes included small-for-gestational age (SGA) defined as a birthweight <10th percentile for gestational age, preterm birth, PE, and a composite of perinatal outcomes (stillbirth, neonatal death, admission to neonatal intensive care unit for ≥48 hours, or birthweight <3rd percentile). While we examined a composite of adverse maternal outcomes (eclampsia, HELLP syndrome [hemolysis, elevated liver function, low platelets], intensive care unit admission, or maternal death), the incidence of these were too low to analyze. Birthweight percentile was calculated using a published birthweight chart for the Australian population, customized for newborn sex.
      • Dobbins T.A.
      • Sullivan E.A.
      • Roberts C.L.
      • Simpson J.M.
      Australian national birthweight percentiles by sex and gestational age, 1998-2007.
      Preterm birth was defined as delivery before 37 weeks of gestation and was analyzed as overall preterm birth, spontaneous preterm birth, and indicated preterm birth. Gestational hypertension was defined as new-onset hypertension (SBP ≥140 mm Hg or DBP ≥90 mm Hg on 2 occasions) in the absence of other features of PE.
      • Tranquilli A.L.
      • Dekker G.
      • Magee L.
      • et al.
      The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP.
      PE was classified according the American College of Obstetrician and Gynecologists 2018 criteria, which defines PE as de novo hypertension after 20 weeks of gestation with 1 or more features of end-organ dysfunction.
      ACOG Practice Bulletin No
      202: Gestational Hypertension and Preeclampsia.
      In the chronic hypertensive population, superimposed PE was defined as “a rise in blood pressure with the development of proteinuria.”
      • Tranquilli A.L.
      • Dekker G.
      • Magee L.
      • et al.
      The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP.
      Perinatal death was defined as “stillbirth or neonatal death of a baby of 20 or more completed weeks of gestation or of 400 grams or more birthweight when gestational age is unknown.”
      Australian Institute of Health and Welfare
      Perinatal deaths in Australia: 2013–2014. Cat. no. PER 94.

      Statistical analyses

      Categorical variables are reported as number and proportion, and continuous variables are reported as mean and standard deviation or median and interquartile range, depending on distribution. BP measurements were categorized according to the ACC criteria as (1) “normal” (SBP <120 mm Hg AND DBP <80 mm Hg), (2) “elevated” (SBP 120–129 mm Hg AND DBP <80 mm Hg), (3) “stage 1 hypertension” (SBP 130–139 mm Hg OR DBP 80–89 mm Hg), and (4) “stage 2 hypertension” (SBP ≥140 mm Hg or DBP ≥90 mm Hg). To identify possible points of change, we also examined the dose–response relationship between BP and pregnancy outcomes by converting MAP, systolic BP, and diastolic BP into 10 equal and incremental groups. All BP measurements were analyzed at <20 weeks, 20–24 weeks, 28–32 weeks, and 34–36 weeks of gestation.
      Relative risk and 95% confidence intervals (95% CIs) were calculated to determine the risk of maternal and pregnancy outcomes in relation to BP categories. Multivariable Poisson regression with robust variance estimate was then performed to calculate adjusted risk ratios (ARRs). Regression models were adjusted for prespecified confounders identified in the literature. These included maternal age, body mass index (BMI), maternal country of birth, parity, smoking, alcohol and drug use, chronic hypertension, preexisting diabetes, systemic lupus erythematosus or antiphospholipid syndrome, and preexisting renal disease.
      • Wright D.
      • Syngelaki A.
      • Akolekar R.
      • Poon L.C.
      • Nicolaides K.H.
      Competing risks model in screening for preeclampsia by maternal characteristics and medical history.
      The relationship between BP at the prespecified gestational ages and pregnancy outcomes was then analyzed within the regression models as both ACC categories and mean arterial pressure. Of note, to ensure that the association between PE and BP was not confounded by measurements recorded after the diagnosis, postdiagnosis BP readings were excluded from analysis. Using the regression models, marginal effect (a measure of the instantaneous effect that a change in BP category has on the predicted probability of each outcome, when the other covariates are kept fixed) also was calculated and plotted.
      There were no data missing for maternal characteristics and pregnancy outcomes with the exception of BMI (n=24) and maternal country of birth (n=9). Blood pressure measurements were available at <20 weeks for 15,223 pregnancies, 20–24 weeks for 13,597 pregnancies, 28–32 weeks for 14,547 pregnancies, and 34–36 weeks for 15,013 pregnancies. Sensitivity analysis was performed for ACC categories with multiple imputation (5 iterations) of missing values of BP. Analyses were conducted using STATA (Released 2019. Version 16.0. STATA/IC for Windows; StataCorp, College Station, TX).

      Results

      Participants and baseline characteristics

      Between January 1, 2016, and July 31, 2018, a total of 23,187 women gave birth to 23,617 neonates at Monash Health. A total of 4944 women were excluded due to multiple pregnancy (n=417), fetal abnormalities (n=676), or no BP readings recorded during the prespecified gestational ages (n=3851). The 3851 women excluded due to lack of BP data are a result of changes in hospital infrastructure from written to electronic records. It is likely that this encompasses a combination of both high- and low-risk women. The remaining 18,243 women were included in the final analysis.
      Maternal characteristics and pregnancy outcomes are summarized in Table 1. The mean age of participants was 30.8 years and median BMI 25.0 kg/m2. Consistent with Australian data, 60.1% of women were multiparous, and rates of chronic hypertension, preexisting diabetes, systemic lupus erythematosus or antiphospholipid syndrome, and renal disease were 0.8%, 1.3%, 0.1%, and 0.2%, respectively.
      Australian Institute of Health and Welfare
      Australia’s mothers and babies 2017—in brief. Perinatal statistics series no. 35. Cat. no. PER 100.
      The median gestation at delivery was 39.3 weeks, mean birthweight was 3314 g, and the rate of SGA was 9.1%. The overall rate of preterm birth was 7.2%. There were 128 perinatal deaths (0.7%) and 297 neonatal intensive care admissions (1.6%). With regards to maternal outcomes, the rate of PE was 3.2%. There were 3 cases of eclampsia (0.02%), 15 cases of HELLP syndrome (0.1%), 53 maternal intensive care admissions (0.3%), and 2 maternal deaths (0.01%). Of the 18,243 women, 824 (4.5%) women were considered “high risk” for PE based on the 2018 American College of Obstetrician and Gynecologists recommendations, of whom 283 (34.3%) received aspirin prophylaxis.
      ACOG Committee Opinion No
      743: Low-Dose Aspirin Use During Pregnancy.
      Of note, those with 2 or more moderate risk factors were not assessed due to lack of data related to family history, socioeconomic status, and interpregnancy interval.
      Table 1Baseline characteristics
      Characteristics or outcomesNo. participants (%)Mean/median (SD/IQR)
      Maternal characteristics
      Age, y18,243 (100)30.8 (5.1)
      BMI, kg/m218,219 (99.9)25.0 (18.0, 32.0)
      Ethnicity
       Australian, New Zealand7384 (40.5)
       South Asia5407 (29.7)
       South East–East Asia3060 (16.8)
       European833 (4.6)
       Eastern, Western, Southern, Middle Africa490 (2.7)
       Northern Africa341 (1.9)
       Polynesia, Melanesia, Micronesia269 (1.5)
       Western Asia260 (1.4)
       South and Central America123 (0.7)
       North America67 (0.4)
      Parity
       Primiparous7286 (39.9)
       Multiparous10,957 (60.1)
      Drug use
       Any smoking2077 (11.4)
       Alcohol use16 (0.1)
       Other drugs229 (1.3)
      Preexisting conditions
       Chronic hypertension151 (0.8)
       Preexisting diabetes233 (1.3)
       Lupus/antiphospholipid syndrome22 (0.1)
       Preexisting renal disease43 (0.2)
      Newborn outcomes
       Gestational age at birth, wk18,243 (100)39.3 (37.4, 41.1)
       Birthweight, g18,243 (100)3314 (583)
       Birthweight ≤10th centile1707 (9.4)
       Birthweight ≤3rd centile387 (2.1)
       Perinatal death128 (0.7)
       NICU admission ≥48 h297 (1.6)
      Maternal and obstetric outcomes
      Hypertensive disorders
       Gestational hypertension213 (1.2)
       Preeclampsia582 (3.2)
      Early-onset preeclampsia (<34 wk)65 (0.4%)
      Late-onset preeclampsia (>34 wk)517 (2.8%)
       HELLP syndrome15 (0.1)
       Eclampsia3 (0.02)
      Preterm birth
       Overall1308 (7.2)
       Spontaneous preterm birth542 (3.0)
      Spontaneous preterm birth <34 wk154 (0.8)
       Indicated preterm birth766 (4.2)
      Indicated preterm birth <34 wk202 (1.1)
       Maternal intensive care admission53 (0.3)
       Maternal death2 (0.01)
      BMI, body mass index; HELLP, hemolysis, elevated liver function, low platelets; IQR, interquartile range; NICU, neonatal intensive care unit; SD, standard deviation.
      Reddy et al. Challenging the definition of hypertension in pregnancy: a retrospective cohort study. Am J Obstet Gynecol 2020.

      BP and pregnancy outcomes: ACC guidelines

      Table 2 and Supplemental Table 2 summarize the relationship between ACC BP categories and each pregnancy outcome. Data are presented as ARR (Table 2) and unadjusted risk ratio (Supplemental Table 2) as compared with the “normal” BP category. Sensitivity analysis showed a similar pattern of biological gradient between case-wise and multiple imputation datasets (Supplemental Table 3). The risk of developing PE increased with each BP category, and this association was significant across all BP categories and all gestational ages. The risk of PE was 2-fold greater in those with elevated BP (ARR, 2.45; 95% CI, 1.74–3.44 at 34–36 weeks of gestation), 3- to 6-fold greater in stage 1 hypertension (ARR, 6.60; 95% CI, 4.98–8.73 at 34–36 weeks of gestation), and 6- to 16-fold greater in stage 2 hypertension (ARR, 16.50; 95% CI, 11.83–23.01 at 34–36 weeks of gestation). When early-onset PE (<34 weeks of gestation) was assessed, a similar trend was observed with both stage 1 and stage 2 hypertension groups, demonstrating an increased risk of early-onset PE (data not presented). The risk of overall preterm birth was significantly greater across all gestational ages in the stage 1 hypertension (ARR, 1.69; 95% CI, 1.43–2.01 at 28–32 weeks of gestation) and stage 2 hypertension groups (ARR, 5.47; 95% CI, 4.30–6.95 at 34–36 weeks of gestation). This was predominately driven by indicated preterm deliveries. The probability of an adverse composite perinatal outcome was also greater in stage 1 and stage 2 hypertension groups, and this was most significant at 28–32 weeks of gestation (ARR, 1.56; 95% CI, 1.23–1.97 and ARR, 4.56; 95% CI, 3.33–6.24 for stage 1 and stage 2 hypertension, respectively). Overall, the association between SGA and BP was weak, particularly at early gestations. The risk of SGA was similar across all BP categories and only significantly greater in those with stage 2 hypertension after 28 weeks of gestation.
      Table 2Adjusted risk ratio for associations between the 2017 American College of Cardiology BP categories and pregnancy outcomes: case-wise analysis
      BP criteria<20 wk20–24 wk28–32 wk34–36 wk
      Total (no. with outcome)Risk ratio (95% CI)Total (no. with outcome)Risk ratio (95% CI)Total (no. with outcome)Risk ratio (95% CI)Total (no. with outcome)Risk ratio (95% CI)
      Preeclampsia
       Normal BP11,216 (208)1.009636 (219)1.009700 (152)1.009105 (77)1.00
       Elevated BP1929 (105)2.38 (1.88–3.02)2138 (118)2.07 (1.65–2.60)2455 (110)2.49 (1.94–3.20)2577 (59)2.45 (1.74–3.44)
       Stage 1 HTN1871 (136)2.94 (2.34–3.71)1656 (159)3.24 (2.60–4.05)2105 (208)4.95 (3.95–6.20)2839 (193)6.60 (4.98–8.73)
       Stage 2 HTN207 (40)6.45 (4.55–9.14)166 (40)6.60 (4.56–9.57)286 (58)8.84 (6.41–12.18)491 (89)16.50 (11.83–23.01)
      Overall preterm birth
       Normal BP11,216 (720)1.009637 (639)1.009701 (512)1.009106 (302)1.00
       Elevated BP1929 (135)1.02 (0.85–1.22)2138 (174)1.16 (0.99–1.37)2455 (171)1.30 (1.10–1.55)2577 (81)0.92 (0.72–1.18)
       Stage 1 HTN1871 (159)1.21 (1.02–1.44)1656 (166)1.33 (1.12–1.59)2105 (201)1.69 (1.43–2.01)2839 (162)1.63 (1.34–1.97)
       Stage 2 HTN207 (34)1.93 (1.38–2.72)166 (35)2.19 (1.53–3.13)286 (70)3.94 (3.07–5.04)491 (100)5.47 (4.30–6.95)
      Indicated preterm birth
       Normal BP11,216 (419)1.009637 (351)1.009701 (298)1.009106 (174)1.00
       Elevated BP1929 (78)0.96 (0.75–1.22)2138 (96)1.14 (0.90–1.42)2455 (94)1.19 (0.95–1.51)2577 (49)0.96 (0.70–1.31)
       Stage 1 HTN1871 (98)1.16 (0.92–1.45)1656 (111)1.48 (1.18–1.84)2105 (134)1.81 (1.46–2.25)2839 (104)1.74 (1.36–2.23)
       Stage 2 HTN207 (25)2.00 (1.32–3.04)166 (26)2.35 (1.45–3.79)286 (58)4.83 (3.57–6.53)491 (80)7.01 (5.23–9.40)
      Spontaneous preterm birth
       Normal BP11,216 (301)1.009637 (288)1.009701 (214)1.009106 (128)1.00
       Elevated BP1929 (57)1.10 (0.83–1.47)2138 (78)1.21 (0.94–1.56)2455 (77)1.48 (1.13–1.93)2577 (32)0.88 (0.59–1.31)
       Stage 1 HTN1871 (61)1.31 (0.98–1.75)1656 (55)1.13 (0.83–1.54)2105 (67)1.54 (1.15–2.06)2839 (58)1.48 (1.07–2.05)
       Stage 2 HTN207 (9)1.84 (0.98–3.43)166 (9)1.97 (1.07–3.63)286 (12)2.29 (1.30–4.03)491 (20)3.03 (1.82–5.05)
      Small-for-gestational age (birthweight ≤10th centile)
       Normal BP11,216 (1066)1.009637 (925)1.009701 (900)1.009106 (839)1.00
       Elevated BP1929 (154)0.97 (0.82–1.15)2138 (151)0.91 (0.77–1.07)2455 (180)0.87 (0.74–1.03)2577 (196)1.03 (0.88–1.20)
       Stage 1 HTN1871 (152)1.10 (0.93–1.30)1656 (133)1.04 (0.87–1.25)2105 (191)1.19 (1.02–1.39)2839 (237)1.12 (0.97–1.30)
       Stage 2 HTN207 (14)1.19 (0.75–1.87)166 (13)1.33 (0.81–2.20)286 (40)2.36 (1.80–3.08)491 (61)2.16 (1.70–2.75)
      Composite perinatal outcome
       Normal BP11,216 (447)1.009637 (361)1.009701 (308)1.009106 (228)1.00
       Elevated BP1929 (78)0.99 (0.77–1.26)2138 (104)1.27 (1.02–1.59)2455 (77)1.01 (0.79–1.30)2577 (69)1.09 (0.83–1.42)
       Stage 1 HTN1871 (94)1.17 (0.92–1.48)1656 (95)1.41 (1.11–1.79)2105 (109)1.56 (1.23–1.97)2839 (114)1.50 (1.18–1.91)
       Stage 2 HTN207 (16)1.45 (0.87–2.40)166 (23)2.85 (1.74–4.67)286 (47)4.56 (3.33–6.24)491 (29)1.95 (1.28–2.96)
      BP categories are in accordance with the 2017 American College of Cardiology guidelines. Associations were adjusted for maternal age, maternal country of birth, body mass index, parity, smoking, alcohol and drug use and preexisting hypertension, diabetes, systemic lupus erythematosus or antiphospholipid syndrome, and preexisting renal disease.
      BP, blood pressure; CI, confidence interval; HTN, hypertension.
      Reddy et al. Challenging the definition of hypertension in pregnancy: a retrospective cohort study. Am J Obstet Gynecol 2020.
      The predicted probability of each outcome across the 4 BP categories is illustrated in Figure 1. Across all gestational ages, increase in BP category was associated with an increased probability of developing PE. In particular, the probability of developing PE in those with stage 1 hypertension ranged from 5.9% to 8.3%, in comparison with 0.9%–2.4% in the “normal” BP category. Although the trend was less prominent, the probability of preterm birth and adverse perinatal outcomes also increased with each BP category. The predicted probability of SGA was greatest in the stage 2 hypertension group and there was no significant difference in rates of SGA in those with normal BP, elevated BP, or stage 1 hypertension.
      Figure thumbnail gr1
      Figure 1Pregnancy outcomes across BP categories as defined by ACC criteria
      A, Mean predicted probability of developing preeclampsia. B, Mean predicted probability of preterm birth. C, Mean predicted probability of small for gestational age. D, Mean predicted probability of the composite perinatal outcome. The mean predicted probability was determined using Poisson regression model and adjusted for age, parity, body mass index, maternal country of birth, smoking, alcohol and drug use, and medical comorbidities (preexisting hypertension, diabetes, systemic lupus erythematosus or antiphospholipid syndrome, and renal disease).
      ACC, American College of Cardiology; BP, blood pressure; HTM, hypertension.
      Reddy et al. Challenging the definition of hypertension in pregnancy: a retrospective cohort study. Am J Obstet Gynecol 2020.

      BP and pregnancy outcomes: MAP

      The relationship between mean arterial pressure and pregnancy outcomes is illustrated in Figure 2, Table 3, and Supplemental Table 4. Across all gestational ages, the risk of developing PE increased with each incremental rise in MAP. This elevation in risk was statistically significant for a MAP ≥85 mm Hg for BP measurements before 32 weeks, and a MAP ≥95 mm Hg for BP measurements at 34–36 weeks of gestation. This dose–response relationship is not as apparent for preterm birth, where rather than an exponential trend, there appears to be a marked increase in risk at a MAP of ≥100 mm Hg. The increase in risk of preterm birth at a MAP ≥100 mm Hg is predominately driven by indicated delivery (data not presented). Similarly, the risk of the composite perinatal outcome increased significantly after a MAP of 90 mm Hg between 20–24 and 28–32 weeks of gestation. The risk of SGA was also greater in those with a MAP ≥100 mm Hg and at 28 weeks of gestation. There appeared to be a U-shaped relationship between MAP at 34–36 weeks of gestation and SGA risk, with a nadir between 65 and 90 mm Hg. Systolic and diastolic BP were also analyzed separately and demonstrated similar results with regards to the outcomes of PE, preterm birth, and the composite perinatal outcome (Supplemental Tables 5 and 6). At all gestational ages, the risk of PE increased significantly from a systolic BP of 110–114.9 mm Hg and a diastolic BP of 70–74.9 mm Hg (MAP 83–88 mm Hg). The risk of preterm birth and adverse perinatal outcomes also increased from a systolic BP of 130–134.9 mm Hg and diastolic BP of 80–84.9 mm Hg (MAP 97–102 mm Hg) and this was most significant at or after 28 weeks of gestation.
      Figure thumbnail gr2
      Figure 2Pregnancy outcomes across mean arterial pressure categories
      A, Mean predicted probability of developing preeclampsia. B, Mean predicted probability of preterm birth. C, Mean predicted probability of small for gestational age. D, Mean predicted probability of the composite perinatal outcome. The mean predicted probability was determined using Poisson regression model and adjusted for age, parity, body mass index, maternal country of birth, smoking, alcohol and drug use, and medical comorbidities (preexisting hypertension, diabetes, systemic lupus erythematosus or antiphospholipid syndrome, and renal disease).
      Reddy et al. Challenging the definition of hypertension in pregnancy: a retrospective cohort study. Am J Obstet Gynecol 2020.
      Table 3Adjusted risk ratios for associations between MAP categories and pregnancy outcomes: case-wise analysis
      MAP (mm Hg)<20 weeks20–24 wk28–32 wk34–36 wk
      Total (no. with outcome)Risk ratio (95% CI)Total (no. with outcome)Risk ratio (95% CI)Total (no. with outcome)Risk ratio (95% CI)Total (no. with outcome)Risk ratio (95% CI)
      Preeclampsia
       <65432 (5)1.00398 (4)1.00264 (1)1.00169 (1)1.00
       65–69.9756 (10)1.09 (0.38–3.17)587 (9)1.55 (0.48–4.99)467 (1)0.52 (0.03–8.30)343 (0)
       70–74.93611 (37)0.84 (0.33–2.13)3042 (51)1.63 (0.59–4.46)2794 (26)2.15 (0.29–15.77)2366 (8)0.53 (0.07–4.19)
       75–79.92839 (53)1.41 (0.57–3.50)2577 (52)1.80 (0.66–4.93)2597 (40)3.37 (0.46–24.48)2394 (14)0.87 (0.12–6.60)
       80–84.93352 (86)1.84 (0.75–4.51)3222 (111)2.93 (1.09–7.87)3662 (87)5.05 (0.70–36.17)3769 (53)2.03 (0.28–14.56)
       85–89.91907 (98)3.38 (1.38–8.30)1804 (100)4.46 (1.65–12.04)2129 (94)8.56 (1.19–61.40)2300 (47)2.79 (0.39–20.19)
       90–94.91518 (104)4.31 (1.76–10.56)1337 (101)5.68 (2.10–15.37)1723 (132)14.21 (1.99–101.64)2234 (111)6.36 (0.89–45.44)
       95–99.9576 (57)5.45 (2.17–13.68)468 (64)9.48 (3.47–25.93)611 (83)23.05 (3.20–165.91)863 (79)11.20 (1.56–80.52)
       100–104.9156 (19)7.07 (2.64–18.92)124 (31)13.81 (4.86–39.22)186 (33)27.53 (3.75–202.08)310 (50)20.55 (2.84–148.89)
       ≥10576 (20)12.81 (4.79–34.26)37 (13)20.54 (6.63–63.60)113 (31)42.63 (5.82–312.44)264 (55)24.27 (3.35–175.90)
      Overall preterm birth
       <65432 (30)1.00398 (26)1.00264 (16)1.00169 (3)1.00
       65–69.9756 (50)0.97 (0.63–1.50)588 (48)1.23 (0.78–1.94)467 (27)0.96 (0.53–1.73)343 (8)1.34 (0.36–4.95)
       70–74.93611 (236)0.94 (0.65–1.36)3042 (208)1.02 (0.69–1.52)2794 (138)0.83 (0.51–1.36)2366 (61)1.43 (0.45–4.50)
       75–79.92839 (169)0.85 (0.58–1.23)2577 (144)0.80 (0.54–1.20)2598 (145)0.91 (0.56–1.49)2395 (91)2.09 (0.67–6.51)
       80–84.93352 (223)0.91 (0.63–1.32)3222 (227)1.00 (0.68–1.48)3662 (209)0.93 (0.58–1.52)3769 (134)1.99 (0.64–6.20)
       85–89.91907 (137)0.98 (0.66–1.43)1804 (136)1.05 (0.70–1.58)2129 (132)1.00 (0.61–1.64)2300 (79)1.92 (0.61–6.02)
       90–94.91518 (122)1.05 (0.71–1.55)1337 (144)1.43 (0.95–2.16)1723 (142)1.31 (0.80–2.15)2234 (97)2.35 (0.75–7.36)
       95–99.9576 (47)0.97 (0.61–1.52)468 (36)1.00 (0.62–1.63)611 (63)1.62 (0.96–2.76)863 (54)3.43 (1.08–10.90)
       100–104.9156 (19)1.52 (0.88–2.65)124 (36)3.17 (1.93–5.22)186 (37)2.75 (1.56–4.84)310 (40)7.00 (2.18–22.53)
       ≥10576 (20)2.46 (1.39–4.35)37 (10)2.75 (1.29–5.85)113 (46)5.87 (3.44–10.02)264 (78)15.25 (4.84–48.04)
      Small-for-gestational age (birthweight <10th centile)
       <65432 (49)1.00398 (41)1.00264 (22)1.00169 (25)1.00
       65–69.9756 (77)0.96 (0.69–1.34)588 (63)1.06 (0.74–1.52)467 (44)1.03 (0.63–1.68)343 (22)0.44 (0.26–0.74)
       70–74.93611 (348)0.93 (0.70–1.23)3042 (272)0.92 (0.68–1.25)2794 (258)1.08 (0.72–1.64)2366 (218)0.64 (0.44–0.93)
       75–79.92839 (243)0.89 (0.67–1.19)2577 (226)0.96 (0.70–1.30)2598 (224)1.06 (0.69–1.61)2395 (188)0.58 (0.40–0.85)
       80–84.93352 (278)0.89 (0.67–1.18)3222 (271)0.95 (0.70–1.29)3662 (290)1.02 (0.67–1.55)3769 (284)0.58 (0.40–0.84)
       85–89.91907 (153)0.94 (0.70–1.28)1804 (141)0.95 (0.69–1.32)2129 (154)0.99 (0.64–1.52)2300 (169)0.60 (0.41–0.88)
       90–94.91518 (124)0.99 (0.72–1.36)1337 (108)1.02 (0.72–1.43)1723 (147)1.18 (0.77–1.82)2234 (170)0.64 (0.43–0.94)
       95–99.9576 (40)0.90 (0.60–1.34)468 (37)1.06 (0.69–1.63)611 (53)1.36 (0.84–2.21)863 (68)0.73 (0.48–1.12)
       100–104.9156 (11)1.03 (0.55–1.95)124 (16)1.73 (0.99–3.02)186 (23)1.89 (1.08–3.30)310 (41)1.31 (0.82–2.08)
       ≥10576 (9)1.28 (0.65–2.54)37 (4)1.38 (0.52–3.67)113 (30)3.81 (2.26–6.44)264 (42)1.50 (0.95–2.36)
      Composite perinatal outcome
       <65432 (24)1.00398 (9)1.00264 (3)1.00169 (5)1.00
       65–69.9756 (22)0.54 (0.31–0.95)588 (19)1.45 (0.66–3.18)467 (14)2.48 (0.74–8.32)343 (2)0.20 (0.04–1.01)
       70–74.93611 (148)0.74 (0.49–1.12)3042 (121)1.77 (0.90–3.46)2794 (77)2.34 (0.76–7.15)2366 (52)0.73 (0.30–1.81)
       75–79.92839 (95)0.61 (0.40–0.94)2577 (92)1.54 (0.78–3.05)2598 (87)2.84 (0.93–8.68)2395 (60)0.85 (0.34–2.08)
       80–84.93352 (147)0.77 (0.51–1.17)3222 (128)1.70 (0.87–3.33)3662 (127)2.97 (0.98–9.00)3769 (96)0.85 (0.35–2.07)
       85–89.91907 (81)0.76 (0.49–1.19)1804 (85)2.00 (1.00–3.97)2129 (65)2.64 (0.86–8.10)2300 (68)1.00 (0.41–2.44)
       90–94.91518 (67)0.74 (0.47–1.18)1337 (79)2.42 (1.21–4.86)1723 (85)4.16 (1.36–12.74)2234 (85)1.22 (0.50–2.97)
       95–99.9576 (32)0.86 (0.50–1.47)468 (25)2.20 (1.02–4.72)611 (33)4.66 (1.47–14.79)863 (33)1.26 (0.50–3.20)
       100–104.9156 (10)1.05 (0.50–2.18)124 (17)4.83 (2.15–10.87)186 (21)8.47 (2.58–27.73)310 (20)2.03 (0.76–5.41)
       ≥10576 (9)1.32 (0.61–2.86)37 (8)7.41 (2.69–20.43)113 (29)19.71 (6.23–62.33)264 (19)2.03 (0.75–5.47)
      Associations were adjusted for maternal age, maternal country of birth, body mass index, parity, smoking, alcohol and drug use and preexisting hypertension, diabetes, systemic lupus erythematosus or antiphospholipid syndrome, and preexisting renal disease.
      BP, blood pressure; CI, confidence interval; HTN, hypertension; MAP, mean arterial pressure.
      Reddy et al. Challenging the definition of hypertension in pregnancy: a retrospective cohort study. Am J Obstet Gynecol 2020.

      Comment

      Principal findings

      Our findings add to the body of evidence that lower BPs currently accepted in clinical practice as normal are also associated with an increased risk of PE. Furthermore, we have demonstrated that this relationship is a continuum, and the relative risk increases exponentially from a MAP of 85–95 mm Hg. Interestingly, we have also demonstrated that women with prehypertensive BPs (stage 1 hypertension or a MAP ≥90–100 mm Hg) are at an increased relative risk of preterm birth and adverse perinatal outcomes.

      Results of the study in the context of other observations

      Various studies have shown that in the first and second trimester, stage 1 hypertension is associated with an increased incidence of PE.
      • Hu J.
      • Li Y.
      • Zhang B.
      • et al.
      Impact of the 2017 ACC/AHA guideline for high blood pressure on evaluating gestational hypertension-associated risks for newborns and mothers.
      • Sutton E.F.
      • Hauspurg A.
      • Caritis S.N.
      • Powers R.W.
      • Catov J.M.
      Maternal outcomes associated with lower range stage 1 hypertension.
      • Hauspurg A.
      • Parry S.
      • Mercer B.M.
      • et al.
      Blood pressure trajectory and category and risk of hypertensive disorders of pregnancy in nulliparous women.
      In a prospective study of 2947 women, Sutton et al
      • Sutton E.F.
      • Hauspurg A.
      • Caritis S.N.
      • Powers R.W.
      • Catov J.M.
      Maternal outcomes associated with lower range stage 1 hypertension.
      demonstrated that stage 1 hypertension is associated with a 2- to 3-fold increased risk of PE in comparison with the normotensive group. Our study supports this finding in a larger population. Furthermore, using MAP, we have demonstrated that the increased risk of PE does not just apply to the stage 1 and stage 2 hypertension groups but rather increases with each incremental rise in MAP. This suggests that rather than a dichotomous separation at 140/90 mm Hg, there is a dose–response relationship between BP and PE, and perhaps the optimal threshold for defining hypertension in pregnancy is even lower at a MAP of 85–95 mm Hg.
      Possibly of greater clinical significance is the relationship between BP, preterm birth, and adverse perinatal outcomes. This study demonstrated an increased risk of preterm birth and adverse perinatal outcomes at a MAP ≥100 mm Hg and in stage 1 and stage 2 hypertension groups. Nonetheless, the group that assumes the most clinically significant risk of these outcomes is the stage 2 hypertension group or those with a MAP ≥105 mm Hg. These latter thresholds correlate with the current definition of hypertension in pregnancy as SBP ≥140 mm Hg or a DBP ≥90 mm Hg. In the literature, the few studies examining these outcomes have shown disparate results. Sutton et al have demonstrated a 4-fold increased risk of preterm birth in those with stage 1 hypertension. In contrast, Hu et al
      • Hu J.
      • Li Y.
      • Zhang B.
      • et al.
      Impact of the 2017 ACC/AHA guideline for high blood pressure on evaluating gestational hypertension-associated risks for newborns and mothers.
      demonstrated no significant difference in preterm birth rates in the stage 1 hypertension group in comparison with the normotensive population. To our knowledge, no other studies have examined the relationship between BP categorized in accordance with the ACC guidelines, and a composite of adverse perinatal outcomes.

      Clinical and research implications

      The results of this study support the view that SBP ≥140 mm Hg or DBP ≥90 mm Hg may not be the ideal threshold for identifying women at risk of hypertensive disorders of pregnancy. As a corollary, the HAPO study (Hyperglycemia and Adverse Pregnancy Outcomes) demonstrated a continuous relationship between glycemic levels and adverse pregnancy outcomes.
      • Metzger B.E.
      • Lowe L.P.
      • et al.
      HAPO Study Cooperative Research Group
      Hyperglycemia and adverse pregnancy outcomes.
      This landmark study has steered changes to pregnancy guidelines, which now recommend lower glucose thresholds for the diagnosis of gestational diabetes, thus identifying a broader group of women who are at risk of the associated adverse events. However, these guidelines have not been adopted by the American society, due to lacking evidence that intervention at lower glycemic levels improves pregnancy outcomes. Similarly, we have demonstrated that 5%–8% of women with stage 1 hypertension will develop PE in comparison to the baseline risk of 1%–2% in the normotensive population. We have also demonstrated that this risk appears to increase significantly at even lower thresholds (MAP 85–95 mm Hg). Although less significant, we have also shown that the prehypertensive group are at an increased of preterm birth and adverse perinatal outcomes. This is particularly important as BP is currently used as a screening tool for PE and is only one part of a heterogenous syndrome that culminates in these adverse outcomes. Therefore, as a screening tool, lower thresholds may be more appropriate in identifying a larger group of women that could benefit from further investigation, closer monitoring, and at earlier gestations interventions such as aspirin prophylaxis. However, similar to the controversies in gestational diabetes, before implementation there is a need for evidence that identification and intervention within this population group would improve pregnancy outcomes.
      One should also understand that BP does not exist in isolation and when screening women for PE, other risk factors should be considered. The poor predictive value of BP alone is highlighted by our study, as the majority of women with elevated, stage 1 and stage 2 hypertension do not develop PE or the associated adverse outcomes. Perhaps, a multifactorial risk assessment is more appropriate for the prediction of PE and adverse outcomes rather than BP alone. The Fetal Medicine Foundation has developed a predictive algorithm for PE using a combination of maternal characteristics, MAP, uterine artery Doppler, and biochemical markers such as placental growth factor and soluble fms-like tyrosine kinase-1.
      • O'Gorman N.
      • Wright D.
      • Syngelaki A.
      • et al.
      Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 11-13 weeks gestation.
      • Gallo D.M.
      • Wright D.
      • Casanova C.
      • Campanero M.
      • Nicolaides K.H.
      Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 19-24 weeks' gestation.
      • Tsiakkas A.
      • Saiid Y.
      • Wright A.
      • Wright D.
      • Nicolaides K.H.
      Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 30-34 weeks' gestation.
      This algorithm has a detection rate of 75%, 85%, and 98% (10% false-positive rate) for preterm PE in the first, second and third trimesters, respectively, which outperforms risk assessment with BP alone.
      • O'Gorman N.
      • Wright D.
      • Syngelaki A.
      • et al.
      Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 11-13 weeks gestation.
      • Gallo D.M.
      • Wright D.
      • Casanova C.
      • Campanero M.
      • Nicolaides K.H.
      Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 19-24 weeks' gestation.
      • Tsiakkas A.
      • Saiid Y.
      • Wright A.
      • Wright D.
      • Nicolaides K.H.
      Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 30-34 weeks' gestation.
      Certainly, further studies are required before recommending a change of practice. There needs to be careful consideration of the trade-off between sensitivity and specificity and resource implications when implementing a lower BP threshold. A lower threshold will likely increase detection rates for PE at the expense of a greater false-positive rate. For example, in this study if we were to implement further evaluation for all those with stage 1one hypertension, approximately 10%–15% of the population would require additional monitoring in comparison with the 1%–3% that currently undergo evaluation for PE. Furthermore, there is no literature to support that closer monitoring and earlier intervention in the prehypertensive phase changes outcomes. As such, intervention studies within the prehypertensive group are essential. This may include a randomized control trial in which maternal and perinatal outcomes are assessed in women with stage 1 hypertension who are randomized to routine clinical practice or closer monitoring with tighter BP control.

      Strengths and limitations

      The strengths of this study lie in its large sample size and the heterogenous population group, which allows for greater generalizability of the findings. Furthermore, as we have used clinically collected data, the results are reflective of routine clinical practice and have greater applicability. This study is also unique in that we have not limited our analysis to the predefined ACC criteria. Through examining mean arterial pressure, we have also analyzed the relationship as a continuum to identify perhaps more relevant thresholds to pregnancy. An inherent limitation remains in the retrospective study design, which can be associated with inaccurate record keeping, interobserver variability in BP measurement, and an inability to control for all confounding factors. However, to minimize the impact of this design, all adverse pregnancy outcomes were confirmed by thorough examination of individual patient records. Another limitation exists in the volume of missing data. Although analysis revealed that the data is likely missing at random and multiple imputation did not show any difference in results, it is important to recognize that this may have influenced the results. To overcome such limitations, a prospective study with consistent measurement of BP is required.

      Conclusion

      This study demonstrates a dose–response relationship between BP and PE, thereby showing that PE and the associated adverse outcomes are not exclusive to those with BPs greater than 140/90 mm Hg. Therefore, consideration of lower BP thresholds in pregnancy is required as women with prehypertensive BPs may benefit from further investigation. However, before implementation, further research is needed to determine whether identification, closer monitoring, and intervention in these women will improve maternal and perinatal outcomes.

      Acknowledgments

      The authors thank Ms Amanda Kendell for her assistance in providing the Birthing Outcomes System database used for this project. Ms Amanda Kendall is employed by Monash Women’s, Monash Health and declares no conflicts of interest or funding.

      Supplementary Materials

      Supplemental Table 1Variables extracted from the Birthing Outcomes System
      Variables
      Maternal and pregnancy characteristicsAge at delivery
      Country of birth
      Height, cm
      Weight, kg
      Body mass index, kg/m2
      Preexisting medical conditions:
      - chronic hypertension
      - preexisting diabetes
      - systemic lupus erythematosus
      - antiphospholipid syndrome
      - preexisting renal disease
      Smoking, alcohol, drug use
      Gravidity
      Parity
      Plurality
      Blood pressure measurementsBooking (<20 wk)
      20–24 wk
      28–32 wk
      34–36 wk
      Pregnancy outcome dataGestational age at delivery
      Onset of labor
      Mode of delivery
      Birthweight, g
      Maternal obstetric complications
      - Pregnancy-induced hypertension
      - Preeclampsia
      - Placental abruption
      - Intensive care admission
      - Maternal death
      Perinatal complications
      - Stillbirth or neonatal death
      - Admission to neonatal intensive care unit for ≥ 48 hours.
      Pregnancy outcome data also were confirmed through manual review of medical records.
      Reddy et al. Challenging the definition of hypertension in pregnancy: a retrospective cohort study. Am J Obstet Gynecol 2020.
      Supplemental Table 2Unadjusted risk ratios for associations between the 2017 American College of Cardiology BP categories and pregnancy outcomes using case-wise analysis
      <20 wk

      Unadjusted RR (95% CI)
      20-24 wk

      Unadjusted RR (95% CI)
      28-32 wk

      Unadjusted RR (95% CI)
      34-36 wk

      Unadjusted RR (95% CI)
      Preeclampsia
       Normal BP1.001.001.001.00
       Elevated BP2.94 (2.33–3.69)2.43 (1.95–3.02)2.86 (2.25–3.64)2.71 (1.93–3.79)
       Stage 1 HTN3.92 (3.18–4.84)4.23 (3.47–5.15)6.31 (5.14–7.73)8.04 (6.19–10.44)
       Stage 2 HTN10.42 (7.65–14.20)10.60 (7.85–14.31)12.94 (9.79–17.10)21.44 (16.02–28.68)
      Overall preterm birth
       Normal BP1.001.001.001.00
       Elevated BP1.09 (0.91–1.30)1.23 (1.04–1.44)1.32 (1.12–1.56)0.95 (0.74–1.21)
       Stage 1 HTN1.32 (1.12–1.56)1.51 (1.28–1.78)1.81 (1.55–2.12)1.72 (1.43–2.07)
       Stage 2 HTN2.56 (1.87–3.51)3.18 (2.35–4.31)4.64 (3.72–5.78)6.14 (4.99–7.55)
      Indicated preterm birth
       Normal BP1.001.001.001.00
       Elevated BP1.08 (0.85–1.37)1.23 (0.99–1.54)1.25 (0.99–1.57)1.00 (0.73–1.36)
       Stage 1 HTN1.40 (1.13–1.74)1.84 (1.50–2.26)2.07 (1.70–2.53)1.92 (1.51–2.44)
       Stage 2 HTN3.23 (2.21–4.72)4.30 (2.98–6.21)6.60 (5.11–8.52)8.53 (6.65–10.93)
      Spontaneous preterm birth
       Normal BP1.001.001.001.00
       Elevated BP1.10 (0.83–1.46)1.22 (0.95–1.56)1.42 (1.10–1.84)0.88 (0.60–1.30)
       Stage 1 HTN1.21 (0.93–1.59)1.11 (0.84–1.48)1.44 (1.10–1.89)1.45 (1.07–1.98)
       Stage 2 HTN1.62 (0.85–3.101.81 (0.95–3.46)1.90 (1.08–3.36)2.90 (1.82–4.60)
      Small-for-gestational age (birthweight ≤10th centile)
       Normal BP1.001.001.001.00
       Elevated BP0.84 (0.71–0.99)0.74 (0.62–0.87)0.79 (0.68–0.92)0.83 (0.71–0.96)
       Stage 1 HTN0.85 (0.72–1.01)0.84 (0.70–1.00)0.98 (0.84–1.14)0.91 (0.79–1.04)
       Stage 2 HTN0.71 (0.43–1.18)0.82 (0.48–1.38)1.51 (1.12–2.02)1.35 (1.06–1.72)
      Composite perinatal outcome
       Normal BP1.001.001.001.00
       Elevated BP1.01 (0.80–1.28)1.30 (1.05–1.61)0.99 (0.77–1.26)1.07 (0.82–1.39)
       Stage 1 HTN1.26 (1.01–1.57)1.53 (1.23–1.91)1.63 (1.32–2.02)1.60 (1.29–2.00)
       Stage 2 HTN1.94 (1.20–3.13)3.70 (2.50–5.48)5.18 (3.90–6.87)2.36 (1.62–3.43)
      BP, blood pressure; CI, confidence interval; HTN, hypertension; RR, risk ratio.
      Reddy et al. Challenging the definition of hypertension in pregnancy: a retrospective cohort study. Am J Obstet Gynecol 2020.
      Supplemental Table 3Adjusted risk ratios for associations between the 2017 American College of Cardiology blood pressure categories and pregnancy outcomes using data with multiple imputations (5 iterations)
      <20 wk

      Risk ratio (95% CI)
      20–24 wk

      Risk ratio (95% CI)
      28–32 wk

      Risk ratio (95% CI)
      34–36 wk

      Risk ratio (95% CI)
      Preeclampsia
       Normal BP1.001.001.001.00
       Elevated BP2.30 (1.80–2.93)2.00 (1.49–2.69)2.42 (1.89–3.10)2.25 (1.61–3.16)
       Stage 1 HTN2.67 (2.13–3.35)2.99 (2.38–3.75)4.54 (3.61–5.70)5.83 (4.46–7.62)
       Stage 2 HTN5.47 (3.93–7.60)5.71 (3.98–8.20)7.88 (5.73–10.83)14.09 (10.21–19.45)
      Overall preterm birth
       Normal BP1.001.001.001.00
       Elevated BP1.02 (0.85–1.22)1.14 (0.98–1.33)1.28 (1.08–1.52)1.02 (0.85–1.23)
       Stage 1 HTN1.23 (1.04–1.44)1.30 (1.09–1.54)1.55 (1.33–1.81)1.37 (1.14–1.65)
       Stage 2 HTN1.78 (1.26–2.51)2.01 (1.28–3.16)3.05 (2.38–3.91)3.16 (2.60–3.84)
      Indicated preterm birth
       Normal BP1.001.001.001.00
       Elevated BP0.99 (0.78–1.25)1.11 (0.89–1.38)1.17 (0.92–1.48)1.06 (0.82–1.38)
       Stage 1 HTN1.22 (0.99–1.51)1.41 (1.15–1.71)1.62 (1.31–1.99)1.49 (1.18–1.88)
       Stage 2 HTN1.92 (1.29–2.87)2.14 (1.31–3.50)3.94 (2.97–5.23)4.10 (3.08–5.46)
      Spontaneous preterm birth
       Normal BP1.001.001.001.00
       Elevated BP1.06 (0.81–1.39)1.20 (0.93–1.54)1.44 (1.15–1.81)0.98 (0.73–1.31)
       Stage 1 HTN1.24 (0.95–1.62)1.13 (0.80–1.62)1.47 (1.12–1.92)1.24 (0.98–1.58)
       Stage 2 HTN1.55 (0.81–2.96)1.81 (0.85–3.88)1.57 (0.88–2.83)1.91 (1.21–3.01)
      Small-for-gestational age (birthweight ≤10th centile)
       Normal BP1.001.001.001.00
       Elevated BP1.00 (0.84–1.20)0.92 (0.80–1.07)0.93 (0.76–1.13)1.05 (0.89–1.23)
       Stage 1 HTN1.11 (0.94–1.31)1.04 (0.85–1.26)1.14 (0.96–1.34)1.10 (0.90–1.33)
       Stage 2 HTN1.16 (0.71–1.89)1.28 (0.79–2.08)1.98 (1.48–2.64)1.91 (1.51–2.41)
      Composite perinatal outcome
       Normal BP1.001.001.001.00
       Elevated BP1.05 (0.80–1.39)1.17 (0.94–1.45)1.07 (0.85–1.34)1.09 (0.86–1.38)
       Stage 1 HTN1.17 (0.93–1.47)1.32 (1.00–1.72)1.37 (1.08–1.73)1.33 (1.02–1.72)
       Stage 2 HTN1.42 (0.76–2.65)2.29 (1.37–3.81)2.95 (2.15–4.06)1.74 (1.28–2.37)
      Blood pressure categories are in accordance with the 2017 American College of Cardiology Hypertension guidelines. Associations were adjusted for maternal age, maternal country of birth, body mass index, parity, smoking, alcohol and drug use, preexisting hypertension, diabetes, systemic lupus erythematosus or antiphospholipid syndrome, and pre-existing renal disease.
      BP, blood pressure; CI, confidence interval; HTN, hypertension.
      Reddy et al. Challenging the definition of hypertension in pregnancy: a retrospective cohort study. Am J Obstet Gynecol 2020.
      Supplemental Table 4Unadjusted risk ratios for associations between the mean arterial pressure categories and pregnancy outcomes using case-wise analysis
      <20 wk

      Unadjusted RR (95% CI)
      20–24 wk

      Unadjusted RR (95% CI)
      28–32 wk

      Unadjusted RR (95% CI)
      34–36 wk

      Unadjusted RR (95% CI)
      Preeclampsia
       <651.001.001.001.00
       65–69.91.14 (0.39–3.32)1.52 (0.47–4.91)0.57 (0.04–9.00)N/A
       70–74.90.89 (0.35–2.24)1.67 (0.61–4.59)2.46 (0.33–18.03)0.57 (0.07–4.54)
       75–79.91.61 (0.65–4.01)2.01 (0.73–5.52)4.06 (0.56–29.45)0.99 (0.13–7.47)
       80–84.92.22 (0.90–5.43)3.43 (1.27–9.24)6.27 (0.88–44.85)2.38 (0.33–17.08)
       85–89.94.44 (1.82–10.84)5.52 (2.04–14.90)11.66 (1.63–83.27)3.45 (0.48–24.88)
       90–94.95.92 (2.43–14.43)7.52 (2.78–20.29)20.23 (2.84–144.04)8.40 (1.18–59.77)
       95–99.98.55 (3.46–21.15)13.61 (5.00–37.03)35.86 (5.02–256.26)15.47 (2.17–110.43)
       100–104.910.52 (4.00–27.70)24.88 (8.96–69.09)46.84 (6.46–339.45)27.26 (3.80–195.58)
       ≥10522.74 (8.80–58.74)34.96 (12.01–101.80)72.42 (10.01–524.10)35.21 (4.92–252.04)
      Overall preterm birth
       <651.001.001.001.00
       65–69.90.95 (0.62–1.47)1.25 (0.79–1.98)0.95 (0.52–1.74)1.31 (0.35–4.89)
       70–74.90.94 (0.65–1.36)1.05 (0.71–1.55)0.81 (0.49–1.35)1.45 (0.46–4.58)
       75–79.90.86 (0.59–1.25)0.86 (0.57–1.28)0.92 (0.56–1.52)2.14 (0.68–6.69)
       80–84.90.96 (0.66–1.38)1.08 (0.73–1.60)0.94 (0.58–1.54)2.00 (0.64–6.22)
       85–89.91.03 (0.71–1.51)1.15 (0.77–1.73)1.02 (0.62–1.69)1.93 (0.62–6.06)
       90–94.91.16 (0.79–1.70)1.65 (1.10–2.47)1.36 (0.82–2.24)2.45 (0.78–7.63)
       95–99.91.18 (0.76–1.83)1.18 (0.72–1.92)1.70 (1.00–2.89)3.52 (1.12–11.14)
       100–104.91.75 (1.02–3.02)4.44 (2.80–7.06)3.28 (1.88–5.72)7.27 (2.28–23.15)
       ≥1053.79 (2.27–6.31)4.14 (0.72–1.92)6.72 (3.98–11.35)16.64 (5.34–51.88)
      Small-for-gestational age (birthweight <10th centile)
       <651.001.001.001.00
       65–69.90.90 (0.64–1.26)1.04 (0.72–1.51)1.13 (0.69–1.84)0.43 (0.25–0.75)
       70–74.90.85 (0.64–1.13)0.87 (0.64–1.18)1.11 (0.73–1.68)0.62 (0.42–0.91)
       75–79.90.75 (0.56–1.01)0.85 (0.62–1.17)1.03 (0.68–1.57)0.53 (0.36–0.78)
       80–84.90.73 (0.55–0.97)0.82 (0.60–1.11)0.95 (0.63-.144)0.51 (0.35–0.74)
       85–89.90.71 (0.52–0.96)0.76 (0.55–1.06)0.87 (0.57–1.33)0.50 (0.34–0.73)
       90–94.90.72 (0.53–0.98)0.78 (0.56–1.10)1.02 (0.67–1.57)0.51 (0.35–0.76)
       95–99.90.61 (0.41–0.91)0.77 (0.50–1.17)1.04 (0.65–1.67)0.53 (0.35–0.82)
       100–104.90.62 (0.33–1.16)1.25 (0.73–2.15)1.48 (0.85–2.58)0.89 (0.56–1.42)
       ≥1051.04 (0.54–2.04)1.05 (0.40–2.77)3.19 (1.92–5.27)1.08 (0.68–1.70)
      Composite perinatal outcome
       <651.001.001.001.00
       65–69.90.52 (0.30–0.92)1.43 (0.65–3.13)2.64 (0.77–9.10)0.20 (0.04–1.01)
       70–74.90.74 (0.48–1.12)1.76 (0.90–3.43)2.43 (0.77–7.63)0.74 (0.30–1.84)
       75–79.90.60 (0.39–0.93)1.58 (0.80–3.10)2.95 (0.94–9.25)0.85 (0.34–2.08)
       80–84.90.79 (0.52–1.20)1.76 (0.90–3.43)3.05 (0.98–9.52)0.86 (0.36–2.09)
       85–89.90.76 (0.49–1.19)2.08 (1.06–4.11)2.69 (0.85–8.49)1.00 (0.41–2.44)
       90–94.90.79 (0.50–1.25)2.61 (1.32–5.16)4.34 (1.38–13.63)1.29 (0.53–3.13)
       95–99.91.00 (0.60–1.67)2.36 (1.12–5.00)4.75 (1.47–15.36)1.29 (0.51–3.26)
       100–104.91.15 (0.56–2.36)6.06 (2.77–13.26)9.94 (3.01–32.83)2.18 (0.83–5.71)
       ≥1052.13 (1.03–4.41)9.56 (3.92–23.30)22.58 (7.02–72.63)2.43 (0.93–6.39)
      CI, confidence interval; N/A, not available; RR, risk ratio.
      Reddy et al. Challenging the definition of hypertension in pregnancy: a retrospective cohort study. Am J Obstet Gynecol 2020.
      Supplemental Table 5Adjusted risk ratios for associations between systolic blood pressure categories and pregnancy outcomes using case-wise analysis
      Systolic blood pressure (mm Hg)<20 wk20–24 wk28–32 wk34–36 wk
      Total (no. with outcome)Risk ratio (95% CI)Total (no. with outcome)Risk ratio (95% CI)Total (no. with outcome)Risk ratio (95% CI)Total (no. with outcome)Risk ratio (95% CI)
      Preeclampsia
       <951601 (13)1.001163 (11)1.00965 (3)1.00745 (1)1.00
       95–99.9967 (8)1.00 (0.42–2.41)631 (6)0.99 (0.37–2.66)509 (8)4.86 (1.30–18.17)542 (1)1.36 (0.86–21.64)
       100–104.93044 (45)1.73 (0.94–3.21)2741 (55)2.01 (1.06–3.82)2651 (32)3.60 (1.10–11.73)2372 (9)2.71 (0.34–21.38)
       105–109.91430 (35)2.72 (1.45–5.12)1203 (19)1.51 (0.72–3.17)1163 (12)3.06 (0.86–10.83)1110 (7)4.40 (0.54–35.66)
       110–114.93569 (88)2.64 (1.48–4.72)3336 (98)2.68 (1.44–4.99)3794 (80)5.85 (1.85–18.54)3838 (47)8.36 (1.15–60.69)
       115–119.91042 (41)3.97 (2.13–7.40)890 (39)3.94 (2.02–7.67)1051 (33)8.61 (2.63–28.12)1076 (21)12.93 (1.73–96.35)
       120–124.92182 (113)5.14 (2.89–9.13)2329 (134)4.95 (2.67–9.21)2662 (133)13.00 (4.12–41.03)3038 (94)20.00 (2.77–144.26)
       125–129.9632 (56)8.20 (4.46–15.06)558 (38)5.49 (2.80–10.75)710 (57)19.00 (5.91–61.08)842 (43)31.82 (4.36–232.53)
       130–134.9512 (50)8.63 (4.63–16.10)491 (59)9.00 (4.67–17.35)687 (80)25.96 (8.12–82.96)868 (79)54.03 (7.44–392.11)
       ≥135244 (49)16.27 (8.74–30.30)255 (55)13.59 (6.92–26.66)355 (66)39.90 (12.38–128.60)582 (91)91.81 (12.65–666.41)
      Overall preterm birth
       <951601 (95)1.001163 (86)1.00965 (57)1.00745 (19)1.00
       95–99.9967 (58)1.01 (0.74–1.39)631 (40)0.88 (0.61–1.25)509 (32)1.07 (0.71–1.63)542 (7)0.50 (0.21–1.18)
       100–104.93044 (208)1.12 (0.89–1.42)2741 (182)0.87 (0.68–1.12)2651 (144)0.90 (0.67–1.21)2372 (75)1.25 (0.76–2.05)
       105–109.91430 (86)0.98 (0.74–1.30)1203 (79)0.87 (0.65–1.16)1163 (57)0.79 (0.56–1.13)1110 (47)1.66 (0.98–2.81)
       110–114.93569 (234)1.01 (0.80–1.28)3336 (220)0.82 (0.65–1.05)3794 (201)0.82 (0.64–1.13)3838 (141)1.44 (0.90–2.32)
       115–119.91042 (74)1.10 (0.81–1.48)890 (54)0.77 (0.55–1.06)1051 (57)0.86 (0.60–1.23)1076 (35)1.30 (0.75–2.26)
       120–124.92182 (162)1.13 (0.88–1.45)2329 (209)1.09 (0.85–1.40)2662 (202)1.20 (0.90–1.61)3038 (114)1.46 (0.90–2.37)
       125–129.9632 (46)1.01 (0.72–1.43)558 (40)0.86 (0.59–1.24)710 (55)1.22 (0.84–1.76)842 (26)1.21 (0.67–2.20)
       130–134.9512 (46)1.15 (0.79–1.66)491 (53)1.22 (0.86–1.72)687 (71)1.51 (1.06–2.16)868 (72)2.98 (1.79–4.97)
       ≥135244 (43)2.16 (1.51–3.08)255 (51)1.69 (1.15–2.47)355 (78)2.93 (2.06–4.15)582 (109)6.75 (4.10–11.10)
      Small-for-gestational age (birthweight ≤10th centile)
       <951601 (180)1.001163 (129)1.00965 (123)1.00745 (88)1.00
       95–99.9967 (96)0.89 (0.71–1.12)631 (61)0.91 (0.68–1.21)509 (55)0.88 (0.66–1.18)542 (51)0.82 (0.59–1.13)
       100–104.93044 (316)0.99 (0.84–1.18)2741 (267)0.96 (0.78–1.16)2651 (268)0.84 (0.69–1.03)2372 (235)0.90 (0.72–1.13)
       105–109.91430 (132)0.93 (0.75–1.15)1203 (113)0.97 (0.77–1.23)1163 (91)0.66 (0.51–0.86)1110 (96)0.83 (0.63–1.09)
       110–114.93569 (292)0.85 (0.71–1.02)3336 (304)0.96 (0.79–1.17)3794 (323)0.75 (0.61–0.91)3838 (336)0.85 (0.69–1.06)
       115–119.91042 (89)0.95 (0.75–1.2)890 (76)0.96 (0.73–1.26)1051 (78)0.66 (0.50–0.87)1076 (85)0.80 (0.60–1.06)
       120–124.92182 (193)1.03 (0.85–1.26)2329 (179)0.89 (0.72–1.12)2662 (226)0.83 (0.67–1.02)3038 (249)0.87 (0.69–1.10)
       125–129.9632 (46)0.89 (0.65–1.22)558 (39)0.87 (0.61–1.23)710 (54)0.76 (0.56–1.04)842 (53)0.69 (0.50–0.96)
       130–134.9512 (24)0.61 (0.40–0.94)491 (34)0.93 (0.64–1.35)687 (57)0.88 (0.64–1.20)868 (78)1.04 (0.77–1.40)
       ≥135244 (18)0.97 (0.61–1.54)255 (20)1.05 (0.65–1.70)355 (36)1.15 (0.79–1.68)582 (62)1.32 (0.96–1.81)
      Composite perinatal outcome
       <951601 (65)1.001163 (39)1.00965 (28)1.00745 (15)1.00
       95–99.9967 (27)0.68 (0.44–1.06)631 (23)1.13 (0.68–1.87)509 (11)0.75 (0.38–1.48)542 (7)0.63 (0.26–1.54)
       100–104.93044 (132)1.05 (0.78–1.40)2741 (109)1.18 (0.83–1.70)2651 (90)1.15 (0.76–1.75)2372 (61)1.29 (0.74–2.24)
       105–109.91430 (41)0.69 (0.47–1.02)1203 (41)1.03 (0.67–1.59)1163 (37)1.07 (0.66–1.73)1110 (32)1.45 (0.79–2.65)
       110–114.93569 (148)0.96 (0.72–1.29)3336 (130)1.11 (0.78–1.59)3794 (135)1.20 (0.80–1.79)3838 (103)1.32 (0.77–2.26)
       115–119.91042 (52)1.17 (0.81–1.68)890 (34)1.13 (0.72–1.79)1051 (29)0.94 (0.56–1.57)1076 (30)1.39 (0.76–2.57)
       120–124.92182 (102)1.07 (0.78–1.47)2329 (126)1.54 (1.07–2.23)2662 (92)1.17 (0.77–1.79)3038 (101)1.63 (0.95–2.80)
       125–129.9632 (27)0.91 (0.57–1.44)558 (22)1.11 (0.65–1.88)710 (28)1.32 (0.78–2.24)842 (18)1.04 (0.53–2.08)
       130–134.9512 (20)0.81 (0.48–1.37)491 (29)1.63 (1.00–2.68)687 (48)2.18 (1.34–3.55)868 (33)1.67 (0.89–3.13)
       ≥135244 (21)1.53 (0.92–2.54)255 (30)2.54 (1.48–4.35)355 (43)3.53 (2.14–5.84)582 (40)2.91 (1.58–5.37)
      Associations were adjusted for maternal age, maternal country of birth, body mass index, parity, smoking, alcohol and drug use and preexisting hypertension, diabetes, systemic lupus erythematosus or antiphospholipid syndrome and preexisting renal disease.
      CI, confidence interval.
      Reddy et al. Challenging the definition of hypertension in pregnancy: a retrospective cohort study. Am J Obstet Gynecol 2020.
      Supplemental Table 6Adjusted risk ratios for associations between diastolic blood pressure categories and pregnancy outcomes using case-wise analysis
      <20 wk20–24 wk28–32 wk34–36 wk
      Diastolic blood pressure (mm Hg)Total (no. with outcome)Risk ratio (95% CI)Total (no. with outcome)Risk ratio (95% CI)Total (no. with outcome)Risk ratio (95% CI)Total (no. with outcome)Risk ratio (95% CI)
      Preeclampsia
       <55879 (16)1.00897 (13)1.00696 (6)1.00456 (2)1.00
       55–59.9772 (8)0.57 (0.25–1.32)626 (8)0.90 (0.37–2.14)516 (4)0.87 (0.25–3.07)450 (2)0.48 (0.04–5.22)
       60–64.95733 (84)0.75 (0.44–1.27)5165 (107)1.32 (0.75–2.33)5048 (72)1.46 (0.64–3.35)4465 (36)1.63 (0.39–6.73)
       65–69.91379 (42)1.46 (0.83–2.59)1244 (35)1.62 (0.86–3.03)1211 (25)1.88 (0.78–4.56)1275 (15)2.23 (0.51–9.70)
       70–74.93830 (146)1.72 (1.03–2.87)3624 (160)2.43 (1.39–4.24)4364 (145)3.01 (1.33–6.80)4459 (84)3.40 (0.84–13.81)
       75–79.9875 (56)2.61 (1.50–4.53)623 (40)3.14 (1.70–5.80)841 (52)4.95 (2.13–11.51)1116 (35)5.17 (1.24–21.50)
       80–84.91446 (105)2.84 (1.67–4.83)1230 (113)4.36 (2.46–7.72)1528 (140)7.10 (3.12–16.14)2141 (1218.99 (2.21–36.59)
       85–89.9192 (19)3.45 (1.77–6.72)121 (19)6.24 (3.14–12.37)185 (30)10.93 (4.53–26.39)331 (41)18.46 (4.43–76.97)
       90–94.987 (12)4.52 (2.12–9.61)59 (14)8.15 (3.75–17.70)111 (18)10.10 (4.03–25.33)208 (39)26.66 (6.38–111.37)
       ≥9530 (10)10.39 (4.71–22.91)8 (5)37.36 (16.52–84.51)47 (12)16.85 (6.36–44.66)112 (19)22.31 (5.13–97.09)
      Overall preterm birth
       <55879 (63)1.00897 (70)1.00696 (35)1.00456 (9)1.00
       55–59.9772 (46)0.88 (0.61–1.26)626 (37)0.80 (0.55–1.17)516 (23)0.91 (0.55–1.52)450 (10)1.08 (0.45–2.62)
       60–64.95733 (362)0.89 (0.69–1.15)5165 (330)0.81 (0.64–1.03)5048 (286)1.13 (0.81–1.58)4465 (147)1.58 (0.81–3.06)
       65–69.91379 (82)0.84 (0.61–1.15)1244 (81)0.82 (0.60–1.11)1211 (61)0.97 (0.65–1.45)1275 (44)1.66 (0.82–3.35)
       70–74.93830 (269)0.94 (0.72–1.22)3624 (271)0.90 (0.70–1.16)4364 (265)1.17 (0.83–1.65)4459 (165)1.79 (0.92–3.46)
       75–79.9875 (59)0.86 (0.61–1.22)623 (70)1.34 (0.98–1.84)841 (60)1.37 (0.92–2.04)1116 (40)1.69 (0.83–3.44)
       80–84.91446 (125)1.10 (0.82–1.48)1230 (117)1.05 (0.79–1.40)1528 (133)1.57 (1.10–2.26)2141 (112)2.43 (1.24–4.76)
       85–89.9192 (20)1.23 (0.75–1.99)121 (21)1.74 (1.11–2.73)185 (39)3.63 (2.38–5.53)331 (34)4.96 (2.40–10.24)
       90–94.987 (12)1.49 (0.83–2.66)59 (14)2.06 (1.15–3.69)111 (27)4.24 (2.66–6.78)208 (46)9.78 (4.83–19.79)
       ≥9530 (10)2.68 (1.36–5.29)8 (3)3.84 (1.34–11.04)47 (25)8.41 (5.30–13.33)112 (38)13.23 (6.46–27.09)
      Small-for-gestational age (birthweight ≤10th centile)
       <55879 (94)1.00897 (95)1.00696 (70)1.00456 (46)1.00
       55–59.9772 (74)0.93 (0.70–1.24)626 (64)1.02 (0.76–1.38)516 (47)0.91 (0.65–1.29)450 (43)0.95 (0.64–1.40)
       60–64.95733 (546)0.99 (0.81–1.21)5165 (487)0.95 (0.77–1.16)5048 (464)0.94 (0.75–1.20)4465 (411)0.93 (0.70–1.24)
       65–69.91379 (124)1.01 (0.78–1.29)1244 (95)0.81 (0.62–1.06)1211 (106)0.95 (0.71–1.26)1275 (99)0.79 (0.57–1.09)
       70–74.93830 (333)1.00 (0.80–1.24)3624 (308)0.94 (0.76–1.17)4364 (368)0.94 (0.74–1.20)4459 (357)0.88 (0.66–1.17)
       75–79.9875 (63)0.88 (0.65–1.19)623 (49)0.91 (0.65–1.27)841 (62)0.88 (0.64–1.22)1116 (111)1.08 (0.78–1.49)
       80–84.91446 (128)1.13 (0.88–1.46)1230 (105)1.02 (0.78–1.33)1528 (146)1.12 (0.85–1.47)2141 (182)0.98 (0.73–1.34)
       85–89.9192 (16)1.15 (0.70–1.91)121 (15)1.37 (0.81–2.31)185 (20)1.39 (0.87–2.20)331 (35)1.39 (0.92–2.10)
       90–94.987 (4)0.64 (0.25–1.68)59 (4)0.85 (0.33–2.17)111 (19)2.04 (1.27–3.28)208 (31)1.81 (1.18–2.76)
       ≥9530 (4)1.51 (0.63–3.59)8 (0)N/A47 (9)2.43 (1.24–4.75)112 (18)1.87 (1.13–3.09)
      Composite perinatal outcome
       <55879 (39)1.00897 (29)1.00696 (15)1.00456 (8)1.00
       55–59.9772 (21)0.65 (0.3.9–1.10)626 (17)0.90 (0.50–1.63)516 (11)1.01 (0.47–2.16)450 (8)0.96 (0.37–2.52)
       60–64.95733 (222)0.89 (0.64–1.23)5165 (203)1.20 (0.82–1.76)5048 (161)1.43 (0.85–2.41)4465 (101)1.18 (0.58–2.41)
       65–69.91379 (59)0.99 (0.67–1.46)1244 (40)0.98 (0.61–1.57)1211 (35)1.25 (0.69–2.26)1275 (32)1.28 (0.60–2.77)
       70–74.93830 (160)0.92 (0.65–1.29)3624 (171)1.36 (0.92–2.01)4364 (161)1.63 (0.97–2.74)4459 (124)1.43 (0.70–2.91)
       75–79.9875 (32)0.76 (0.48–1.22)623 (26)1.16 (0.69–1.97)841 (32)1.66 (0.90–3.05)1116 (40)1.72 (0.81–3.66)
       80–84.91446 (79)1.14 (0.77–1.67)1230 (76)1.68 (1.09–2.59)1528 (70)1.90 (1.09–3.32)2141 (87)1.96 (0.95–4.06)
       85–89.9192 (13)1.32 (0.71–2.46)121 (11)2.16 (1.14–4.11)185 (18)3.81 (1.94–7.45)331 (13)1.93 (0.80–4.65)
       90–94.987 (4)0.82 (0.30–2.26)59 (8)2.95 (1.26–6.90)111 (18)6.38 (3.25–12.55)208 (16)3.33 (1.42–7.80)
       ≥9530 (6)2.34 (0.97–5.62)8 (2)6.58 (1.73–24.94)47 (20)15.99 (8.26–30.97)112 (11)3.42 (1.33–8.78)
      Associations were adjusted for maternal age, maternal country of birth, body mass index, parity, smoking, alcohol and drug use and pre-existing hypertension, diabetes, systemic lupus erythematosus or antiphospholipid syndrome, and preexisting renal disease.
      CI, confidence interval.
      Reddy et al. Challenging the definition of hypertension in pregnancy: a retrospective cohort study. Am J Obstet Gynecol 2020.

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