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*Corresponding Author: Maria V. Division of Kidney and Hypertension, Lenox Hill Hospital-Northwell Health/Zucker School of Medicine, New York, NY 10075, USA
Citation: Valerie Barta, Nimesh Shah, Stephanie Baum, Christina Zottolla, Jason Schneider, et al. (2021) Trends in Peripartum Serum N-terminal Brain Natriuretic Peptide (NT-proBNP) levels in Patients with Hypertensive Gestational Syndromes. J. Heart and Vasculature, 1(3); Doi: 10.31579/jhv-2021/014
Copyright: © 2021 Maria V. DeVita, This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 07 April 2021 | Accepted: 06 May 2021 | Published: 11 May 2021
Keywords: NT-proBNP; preeclampsia; gestational hypertension
Pregnancy yields physiologic changes to the cardiac circulatory system and alterations in volume status. Since serum NT-proBNP levels rise in response to cardiac ventricular myocyte stretch, it is not surprising that higher NT-proBNP levels are noted throughout pregnancy even in normotensive pregnancies versus non-pregnancy. Patients with hypertensive disorders of pregnancy have been shown to have higher NT-proBNP levels compared to normal pregnancy. We examined the NT-proBNP levels immediately before and after delivery in non hypertensive women and those with hypertensive gestational syndromes including chronic hypertension (cHTN), gestational hypertension (GH) and preeclampsia (PEC).
A total of 97 patients were enrolled. Thirty-five normotensive controls, 14 in the cHTN group, 29 in the GH group and 19 in the PEC group. The mean antepartum NT-proBNP level in the normotensive control group was 65.4pg/dL, 82.1pg/dL in cHTN group, 64.8pg/dL in the GH group and 133.3pg/dL in the PEC group. There was a trend towards higher antepartum NT-proBNP levels in patients with cHTN and PEC as compared to control. The mean postpartum NT-proBNP level in the control group was 209.2pg/dL, 207.7pg/dL in cHTN group, 259.5pg/dL in the GH group and 198.8pg/dL in the PEC group. We found no significant differences in antepartum (p=0.47) or postpartum (p=0.32) NT-proBNP levels between patients in the normotensive control group, cHTN group, GH group or the PEC group. However, the mean antepartum NT-proBNP levels for all groups combined was 90pg/dL (5-988pg/dL). The mean postpartum NT-proBNP was significantly more elevated at 218.5pg/dl (11-1151pg/dL). The change in NT-proBNP level from antepartum to postpartum was significant across groups (p=0.01). The increase in NT-ProBNP was significantly larger in the gestational HTN group compared to the PEC group (194.7pg/dL vs 65.5pg/dL respectively; p=0.004), as the antepartum level was already markedly elevated in the PEC group. A statistically significantly increase in postpartum NT-proBNP was also noted in normotensive controls compared to PEC (mean rise 143.9pg/dL vs. 65.5pg/dL respectively; p=0.0081). Physiologic increases in serum NT-proBNP may be exaggerated in certain patients with hypertensive disorders of pregnancy. It is thought that elevated NT-pro BNP levels in HGS represent cardiac strain due to the failure of the maternal cardiovascular system to adapt to the demands of pregnancy. When comparing antepartum to postpartum NT-proBNP levels in our 4 designated groups there were no differences. However collectively, post partum levels were elevated compared to antepartum levels showing that this 24-48 hour period is very dynamic in terms of cardiac strain. This difference was most significant in the patients with gestational hypertension and preeclampsia as compared to normal controls and chronic hypertensives. Examining the NT-proBNP levels within this narrow window has not been previously described. More research is needed to elucidate whether there is predictive value of NT-proBNP immediate antepartum or postpartum that we can use to aid in the often-difficult diagnosis of exacerbation of chronic or gestational hypertension versus developing preeclampsia.
Pregnancy is characterized by complex physiological changes of the cardiovascular system including a 40-50% increase in blood volume which increases left ventricular mass, left ventricular end diastolic pressure and cardiac output [1]. Interstitial water and sodium are increasingly retained towards the end of pregnancy and there is a 14
The primary objective of the study was to determine differences in NT-proBNP level associated with hypertensive disorder of pregnancy namely cHTN, GH and PEC, as compared to normal control pregnancy. Predictor and baseline variables includes but not limited to NT-proBNP level, patient’s age, race, parity, BMI and gestational age at delivery, family or personal history of preeclampsia, route of delivery, pre-pregnancy weight, serum creatinine, aspartate and alanine transaminases (AST,ALT), hemoglobin, platelet count, uric acid, lactate dehydrogenase, urine analysis, and urine protein to creatinine ratio.
A crude comparison of hypertensive disorders of pregnancy was performed using univariate multinomial logistic regression. Once the confounders are identified (p < 0>
Assuming that pregnancy induced hypertensive disorders group will have higher NT-pro BNP level, and the log-scale common SD of 0.90, the Bonferroni adjusted two-sample t-test with 0.01 two-sided significance level will have 80% power to detect the difference between these log-scale means when the sample size is 30 subjects per group. Based on above justification we aimed to enroll 30 patients in each group in various category of hypertensive disorders as well as normal control pregnancy (total 120 subjects).
A total of 97 patients were enrolled. Thirty-five normotensive controls, 14 in the cHTN group, 29 in the GH group and 19 in the PEC group. Four patients in each of the cHTN and GH group, and 6 in the normotensive group developed peripartum superimposed PEC. These patients were therefore analyzed in the PEC group, resulting in 29 normotensive controls, 10 patients with cHTN, 25 with GH and 33 in the PEC group. The mean gestational age of patients was 38.6 weeks. Serum creatinine (SCr) ranged from 0.37-1.10 mg/dL, (mean 0.63 mg/dL). The mean time from ante-partum serum blood draw to delivery was 9.28 hours (SD +/- 6.8), mean time from delivery to postpartum draw was 12.9 hours (SD +/- 6.5). Oral antihypertensive requirements (labetalol, nifedipine ER, nifedipine IR) during hospitalization included 3/10 (30%) chronic hypertensives, 4/25 (16%) in GH group and 16/33 (48.5%) of preeclamptics. 9/33 (27.3%) preeclamptics required IV antihypertensives (IV labetalol, IV hydralazine) for severe range blood pressures. Vaginal delivery was the most common delivery mode in each group except for the normotensive group in which 18/29 (62%) of patients had caesarian sections. Ten of the 33 preeclamptic patients (33%) exhibited severe features (Table 1).
The mean antepartum NT-proBNP level in the normotensive control group was 65.4pg/dL, 82.1pg/dL in cHTN group, 64.8pg/dL in the GH group and 133.3pg/dL in the PEC group. Although there was a trend towards higher antepartum NT-proBNP levels in patients with cHTN and PEC as compared to control or GH groups, it was not statistically significant (p > .05) The mean postpartum NT-proBNP level in the control group was 209.2pg/dL, 207.7pg/dL in cHTN group, 259.5pg/dL in the GH group and 198.8pg/dL in the PEC group. We found no significant differences in antepartum (p=0.47) or postpartum (p=0.32) NT-proBNP levels between patients in the normotensive control group, cHTN group, GH group or the PEC group. (Table 2)
The mean antepartum NT-proBNP levels for all groups combined was 90pg/dL (5-988pg/dL). The mean postpartum NT-proBNP was significantly more elevated at 218.5pg/dl (11-1151pg/dL). The change in NT-ProBNP level from antepartum to postpartum (i.e. postpartum – antepartum level) did differ significantly across groups (p=0.01). The increase in NT-ProBNP was significantly larger in the gestational HTN group compared to the PEC group (194.7pg/dL vs 65.5pg/dL respectively; p=0.004), as the antepartum level was already markedly elevated in the PEC group. A statistically significantly increase in postpartum NT-proBNP was also noted in normotensive controls compared to preeclamptics (mean rise 143.9pg/dL vs. 65.5pg/dL respectively; p=0.0081). There was not enough evidence to conclude that the increase in NT-ProBNP level differed between any other two groups. (Table 3).
There was no significant findings on multivariate analysis
Physiologic increases in serum NT-proBNP may be exaggerated in certain patients with hypertensive disorders of pregnancy [17, 18]. It is thought that elevated NT-pro BNP levels in HGS represent cardiac strain due to the failure of the maternal cardiovascular system to adapt to the demands of pregnancy [19-21]. In PEC this failure to adapt is most severe [22]. The rate of preeclampsia in the US increased by 25% between 1987 and 2004 [23]. The incidence of severe PEC increased nearly 7 fold comparing births from 1980 to 2003 [24] highlighting the importance of this issue. NT-proBNP has been tested as an early predictor for the later development of PEC in high risk pregnant women but first and second trimester levels do not consistently correlate with those who go on to develop PEC later in pregnancy. Using NT-proBNP in conjunction with other clinical markers as a diagnostic rather than predictive tool for PEC is less clear. We looked at immediate ante and postpartum NT-pro BNP levels in normal pregnancy, cHTN, GH and PEC to investigate trends in peripartum cardiac strain. When comparing antepartum to postpartum NT-proBNP levels in our 4 designated groups there were no differences. However collectively, post partum levels were elevated compared to antepartum levels showing that this 24-48 hour period is very dynamic in terms of cardiac strain.
Gestational hypertensive disorders are increasingly prevalent in the United States due to increases in co-morbidities, maternal age and infertility interventions. This is the first study to prospectively assess the NT-proBNP levels of pregnant normotensives, chronic hypertensives, gestational hypertensives and preeclamptics pre and post-delivery during the period of maximal pregnancy-related cardiovascular strain. Our data show all groups had higher antepartum NT-proBNP levels compared to non-pregnancy. There was a trend towards higher antepartum NT-proBNP in those with chronic hypertension which we think may be secondary to adaptations to longstanding elevated blood volume and pressure. Those with preeclampsia showed an even larger trend towards higher antepartum NT-proBNP which may be an indicator of impending preeclampsia.. More research is needed to elucidate whether there is a negative predictive value NT-proBNP cut off in immediate antepartum NT-proBNP level or degree of rise in postpartum NT-proBNP that we can use to aid in the often difficult diagnosis of exacerbation of chronic or gestational hypertension versus developing preeclampsia.
Given that our study was a small population, some of our findings, in particular the trend towards higher mean postpartum NT-proBNP levels in our PEC cohort may not have reached statistical significance due to sampling error and other confounding factors. Another important note is that 62% of our normotensive controls underwent elective cesarean sections, compared to 20% in the cHTN group, 40% in GH and 39.4% in the PEC group. We prioritized minimizing interventions in this sensitive study population and as such, we enrolled more normotensive patients with planned C-sections because per hospital protocol they already required at least one blood draw. Higher peripartum NT-BNP levels in the normotensive groups may have been related to intra-op cardiovascular stress, anesthesia, intravenous fluids and blood products.
While using NT-proBNP is a validated marker for cardiac strain, it can be affected by other factors that need to be considered, particularly in pregnancy. Obesity, infection and intrauterine growth restriction can increase NT-proBNP levels [15, 17 and 18]. Lev-Sagie et al [26] reported an increase in NT-proBNP in women receiving epidural pain relief versus not. A study from 2007 by Tihtonen et al (27) published in AJOG found higher levels of NT-proBNP in patients with preeclampsia who were treated with antihypertensives versus not. It is unclear whether these factors cause an independent rise in NT-proBNP regardless of the patient’s hemodynamic status or whether the cardiovascular strain conferred by some of these conditions is what drives the rise in NT-proBNP. In those patients with severe PEC and kidney impairment, the reduced clearance of NT-proBNP may lead to exaggerated elevations in peripartum levels.
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