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Assessment of baseline renal function tests to predict adverse outcomes in women with chronic hypertension

Published:August 07, 2022DOI:https://doi.org/10.1016/j.ajog.2022.08.005

      Objective

      Chronic hypertension is a major health issue, complicating approximately 0.6% to 1.5% of all pregnancies in the United States.
      • Bateman B.T.
      • Bansil P.
      • Hernandez-Diaz S.
      • Mhyre J.M.
      • Callaghan W.M.
      • Kuklina E.V.
      Prevalence, trends, and outcomes of chronic hypertension: a nationwide sample of delivery admissions.
      Because kidneys are the first end organ affected by hypertension, the rate of adverse effects can be related to baseline proteinuria.
      • Sibai B.M.
      • Lindheimer M.
      • Hauth J.
      • et al.
      Risk factors for preeclampsia, abruptio placentae, and adverse neonatal outcomes among women with chronic hypertension. National Institute of Child Health and Human Development Network of maternal-fetal Medicine Units.
      ,
      • Morgan J.L.
      • Nelson D.B.
      • Roberts S.W.
      • Wells C.E.
      • McIntire D.D.
      • Cunningham F.G.
      Association of baseline proteinuria and adverse outcomes in pregnant women with treated chronic hypertension.
      Although the classic cutoff value of urine protein >300 mg/24 h is widely accepted, it is not based on clinical outcomes but rather on expert opinion.
      • Fishel Bartal M.F.
      • Lindheimer M.D.
      • Sibai B.M.
      Proteinuria during pregnancy: definition, pathophysiology, methodology, and clinical significance.
      We sought to examine the relationship between baseline renal function tests and superimposed preeclampsia at <34 weeks’ gestation in women with chronic hypertension.

      Study Design

      This was a retrospective study of pregnant women with chronic hypertension with singleton pregnancies who delivered at ≥20 weeks’ gestation at a tertiary-care center. We excluded women with possible causes of secondary hypertension. Women with missing information for renal function tests (serum creatinine and 24-hour urine protein) before 20 weeks’ gestation were excluded. Our primary outcome was early-onset superimposed preeclampsia, defined as delivery for superimposed preeclampsia with severe features before 34 weeks’ gestation. The association between baseline renal function tests and the primary outcome was assessed using the receiver operating characteristic curve and the area under the curve (AUC). Best cutoff points were determined using the Liu method. Pregnancy outcomes were compared between women with values above and below the cutoffs. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated, controlling for maternal age, body mass index, multiparity, pregestational diabetes mellitus, and low-dose aspirin. Our institutional review board approved this study.

      Results

      Of the 300 women, 51 (17%) had early-onset superimposed preeclampsia (Supplemental Figure). The best cutoffs for baseline serum creatinine, 24-hour urine protein, and protein–creatinine ratio to predict the primary outcome were 0.63 mg/dL (AUC, 0.67; 95% CI, 0.57–0.77), 262 mg/24 h (AUC, 0.66; 95% CI, 0.56–0.76), and 0.15 (AUC, 0.68; 95% CI, 0.61–0.80), respectively. Maternal demographics are presented in Supplemental Table 1, Supplemental Table 2, Supplemental Table 3. Primary and secondary outcomes are presented in the Table. A baseline serum creatinine 0.63 mg/dL vs <0.63 mg/dL was associated with increased odds of the primary outcome (26.8% vs 12.3%; aOR, 2.58 [95% CI, 1.38–4.85]). A baseline urine protein of 262 mg/24 h vs <262 mg/24 h was associated with increased odds of early-onset superimposed preeclampsia (33.0% vs 11.8%; aOR, 3.47 [95% CI, 1.80–6.68]). A baseline protein–creatinine ratio 0.15 vs <0.15 was associated with increased odds of early-onset superimposed preeclampsia (35.1% vs 10.4%; aOR, 4.36 [95% CI, 2.16–8.82]).
      TablePrimary and secondary outcomes
      OutcomesSerum creatinine <0.63 mg/dL (n=203)Serum creatinine ≥0.63 mg/dL (n=97)P valueaOR (95% CI)
      Early-onset superimposed preeclampsia with severe features25 (12.3)26 (26.8)<.012.58 (1.38–4.85)
      Statistically significant.
      Superimposed preeclampsia with severe features64 (31.5)42 (43.3).051.63 (0.98–2.74)
      Iatrogenic preterm delivery <34 wk33 (16.3)34 (35.1)<.0012.79 (1.57–4.93)
      Statistically significant.
      Fetal growth restriction33 (16.3)16 (16.5).961.04 (0.54–2.02)
      Cesarean delivery107 (52.7)59 (60.8).191.28 (0.78–2.12)
      NICU admission85 (42.1)48 (50.0).201.36 (0.82–2.28)
      Urine protein <262 mg/24 h (n=229)Urine protein ≥262 mg/24 h (n=71)P valueaOR (95% CI)
      Early-onset superimposed preeclampsia with severe features27 (11.8)24 (33.0)<.0013.47 (1.80–6.68)
      Statistically significant.
      Superimposed preeclampsia with severe features66 (28.8)40 (56.3)<.0012.78 (1.58–4.90)
      Statistically significant.
      Iatrogenic preterm delivery <34 wk39 (17.0)28 (39.4)<.0012.93 (1.60–5.37)
      Statistically significant.
      Fetal growth restriction39 (17.0)10 (14.1).560.78. (0.36–1.70)
      Cesarean delivery112 (53.6)32 (55.2).830.95 (0.52–1.75)
      NICU admission94 (41.2)39 (55.7).031.53 (0.86–2.72)
      Protein–creatinine ratio <0.15 (n=173)Protein–creatinine ratio ≥0.15 (n=74)P valueaOR (95% CI)
      Early-onset superimposed preeclampsia with severe features18 (10.4)26 (35.1)<.0014.36 (2.16–8.82)
      Statistically significant.
      Superimposed preeclampsia with severe features48 (27.8)42 (56.8)<.0012.98 (1.66–5.36)
      Statistically significant.
      Iatrogenic preterm delivery <34 wk28 (16.2)30 (40.5)<.0013.30 (1.75–6.23)
      Statistically significant.
      Fetal growth restriction28 (16.2)13 (17.6).791.06 (0.50–2.22)
      Cesarean delivery87 (50.3)50 (67.6).011.89 (1.04–3.40)
      Statistically significant.
      NICU admission66 (38.4)45 (61.6)<.012.18 (1.20–3.96)
      Statistically significant.
      Data are shown as number (percentage). Of 300 women, 247 (82%) had data on the protein–creatinine ratio. AORs were controlled for age, body mass index, multiparity, pregestational diabetes mellitus, and low-dose aspirin.
      aOR, adjusted odds ratio; CI, confidence interval; NICU, neonatal intensive care unit.
      Kawakita. Assessment of baseline renal function tests to predict adverse outcomes in women with chronic hypertension. Am J Obstet Gynecol 2022.
      a Statistically significant.

      Conclusion

      Kuper et al
      • Kuper S.G.
      • Tita A.T.
      • Youngstrom M.L.
      • et al.
      Baseline renal function tests and adverse outcomes in pregnant patients with chronic hypertension.
      reported that a baseline urine protein-to-creatinine ratio 0.12 and serum creatinine 0.75 mg/dL were associated with increased odds of early-onset superimposed preeclampsia. Consistent with the previous study, we found that values of serum creatinine 0.63 mg/dL, baseline 24-hour urine protein 262 mg/24 h, and protein–creatinine ratio 0.15, which were much lower than traditional cutoffs, were associated with increased odds of early-onset superimposed preeclampsia and other severe adverse pregnancy outcomes. Our findings suggest that even slight renal function damages could be associated with adverse pregnancy outcomes. Our findings can be used when assessing the risk of early-onset superimposed preeclampsia in women with chronic hypertension.

      Appendix

      Figure thumbnail fx1
      Supplemental FigureCohort diagram
      Kawakita. Assessment of baseline renal function tests to predict adverse outcomes in women with chronic hypertension. Am J Obstet Gynecol 2022.
      Supplemental Table 1Maternal demographics according to 24-hour urine protein
      CharacteristicsUrine protein <262 mg/24 h (n=229)Urine protein 262 mg/24 h (n=71)P value
      Age (y)31.6 (±5.7)30.3 (±6.0).11
      First-trimester body mass index (kg/m2)37.1 (±10.7)40.4 (±11.5).03
      Race.34
       Non-Hispanic Black171 (74.7)51 (71.8)
       Non-Hispanic White48 (21.0)18 (25.4)
       Hispanic1 (0.4)1 (1.4)
       Asian1 (0.4)1 (1.4)
       Other8 (3.5)0 (0)
      Multiparas163 (71.2)39 (54.9).01
      Duration of hypertension.40
       <4 y86 (37.6)27 (38.0)
      4 y81 (35.4)30 (42.3)
       Unknown62 (27.1)14 (19.7)
      Antihypertensive medication prepregnancy144 (62.9)49 (69.0).35
      Pregestational diabetes mellitus58 (25.3)29 (40.9).01
      Low-dose aspirin106 (46.3)33 (46.5).98
      Smoking17 (7.4)1 (1.4).06
      Illicit drug use5 (2.2)0 (0).21
      Baseline renal test.38
       Before 14 wk191 (83.4)56 (78.9)
       14–19 wk38 (16.6)15 (21.1)
      Data are shown as number (percentage) or mean (±standard deviation).
      Kawakita. Assessment of baseline renal function tests to predict adverse outcomes in women with chronic hypertension. Am J Obstet Gynecol 2022.
      Supplemental Table 2Maternal demographics according to serum creatinine
      CharacteristicsSerum creatinine <0.63 mg/dL (n=203)Serum creatinine 0.63 mg/dL (n=97)P value
      Age (y)31.1 (±6.0)31.7 (±5.4).39
      First-trimester body mass index (kg/m2)37.0 (±11.0)39.7 (±10.5).05
      Race.04
       Non-Hispanic Black140 (69.0)82 (84.5)
       Non-Hispanic White54 (26.6)12 (12.4)
       Hispanic2 (1.0)0 (0)
       Asian2 (1.0)0 (0)
       Other5 (2.5)3 (3.1)
      Multiparas139 (68.5)63 (65.0).54
      Duration of hypertension.24
       <4 y83 (40.9)30 (30.9)
      4 y72 (35.5)39 (40.2)
      Unknown48 (23.7)28 (28.9)
      Antihypertensive medication prepregnancy126 (62.1)67 (69.1).24
      Pregestational diabetes mellitus56 (27.6)31 (32.0).44
      Low-dose aspirin93 (45.8)46 (47.4).79
      Smoking14 (6.9)4 (4.1).34
      Illicit drug use4 (2.0)1 (1.0).55
      Baseline renal test.78
       Before 14 wk168 (82.8)79 (81.4)
       14–19 wk35 (17.2)18 (18.6)
      Data are shown as number (percentage) or mean (±standard deviation).
      Kawakita. Assessment of baseline renal function tests to predict adverse outcomes in women with chronic hypertension. Am J Obstet Gynecol 2022.
      Supplemental Table 3Maternal demographics according to protein–creatinine ratio
      CharacteristicsProtein–creatinine ratio <0.15 (n=173)Protein–creatinine ratio 0.15 (n=74)P value
      Age (y)31.9 (5.7)30.9 (6.2).18
      First-trimester BMI (kg/m2)38.0 (10.9)38.6 (11.7).67
      Race.21
       Non-Hispanic Black129 (74.6)55 (74.3)
       Non-Hispanic White36 (20.8)17 (23.0)
       Hispanic1 (0.6)1 (1.4)
       Asian0 (0)1 (1.4)
       Other7 (4.1)0 (0)
      Multiparas122 (70.5)43 (58.1).06
      Duration of hypertension.88
       <4 y68 (39.3)28 (37.8)
      4 y62 (35.8)29 (39.2)
      Unknown43 (24.9)17 (23.0)
      Antihypertensive medication prepregnancy113 (65.3)45 (60.8).50
      Pregestational diabetes mellitus41 (23.7)33 (44.6)<.01
      Low-dose aspirin85 (49.1)34 (46.0).65
      Smoking11 (6.4)2 (2.7).24
      Illicit drug use4 (2.3)0 (0).19
      Baseline renal test.39
       Before 14 wk154 (89.0)63 (85.1)
       14–19 wk19 (11.0)11 (14.9)
      Of 300 women, 247 (82%) had data on the protein–creatinine ratio. Data are shown as number (percentage).
      BMI, body mass index.
      Kawakita. Assessment of baseline renal function tests to predict adverse outcomes in women with chronic hypertension. Am J Obstet Gynecol 2022.

      References

        • Bateman B.T.
        • Bansil P.
        • Hernandez-Diaz S.
        • Mhyre J.M.
        • Callaghan W.M.
        • Kuklina E.V.
        Prevalence, trends, and outcomes of chronic hypertension: a nationwide sample of delivery admissions.
        Am J Obstet Gynecol. 2012; 206 (e1–8): 134
        • Sibai B.M.
        • Lindheimer M.
        • Hauth J.
        • et al.
        Risk factors for preeclampsia, abruptio placentae, and adverse neonatal outcomes among women with chronic hypertension. National Institute of Child Health and Human Development Network of maternal-fetal Medicine Units.
        N Engl J Med. 1998; 339: 667-671
        • Morgan J.L.
        • Nelson D.B.
        • Roberts S.W.
        • Wells C.E.
        • McIntire D.D.
        • Cunningham F.G.
        Association of baseline proteinuria and adverse outcomes in pregnant women with treated chronic hypertension.
        Obstet Gynecol. 2016; 128: 270-276
        • Fishel Bartal M.F.
        • Lindheimer M.D.
        • Sibai B.M.
        Proteinuria during pregnancy: definition, pathophysiology, methodology, and clinical significance.
        Am J Obstet Gynecol. 2022; 226: S819-S834
        • Kuper S.G.
        • Tita A.T.
        • Youngstrom M.L.
        • et al.
        Baseline renal function tests and adverse outcomes in pregnant patients with chronic hypertension.
        Obstet Gynecol. 2016; 128: 93-103