The Journal of Maternal-Fetal & Neonatal Medicine
ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: http://www.tandfonline.com/loi/ijmf20
Is there an association between a history of placental abruption and long-term maternal renal complications? E. S. Arazi, R. Kessous, I. Shoham-Vardi, G. Pariente, R. Sergienko & E. Sheiner To cite this article: E. S. Arazi, R. Kessous, I. Shoham-Vardi, G. Pariente, R. Sergienko & E. Sheiner (2015) Is there an association between a history of placental abruption and long-term maternal renal complications?, The Journal of Maternal-Fetal & Neonatal Medicine, 28:14, 1641-1646, DOI: 10.3109/14767058.2014.967206 To link to this article: http://dx.doi.org/10.3109/14767058.2014.967206
Accepted author version posted online: 19 Sep 2014. Published online: 10 Oct 2014. Submit your article to this journal
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Date: 13 November 2015, At: 03:57
http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, 2015; 28(14): 1641–1646 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.967206
ORIGINAL ARTICLE
Is there an association between a history of placental abruption and long-term maternal renal complications? E. S. Arazi1, R. Kessous1, I. Shoham-Vardi2, G. Pariente1, R. Sergienko2, and E. Sheiner1
Downloaded by [University of California, San Diego] at 03:57 13 November 2015
1
Department of Obstetrics and Gynecology, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel and 2Department of Epidemiology and Health Services Evaluation, Ben-Gurion University of the Negev, Beer-Sheva, Israel Abstract
Keywords
Objective: To investigate whether patients with a history of placental abruption have an increased risk for subsequent maternal long-term morbidity. Study design: A population-based study compared the incidence of long-term renal morbidity in cohort of women with and without a history of placental abruption. Deliveries occurred during a 25-year period, with a mean follow-up duration of 11.2 years. Renal morbidity included kidney transplantation, chronic renal failure, hypertensive renal disease, etc. Results: During the study period 99 354 deliveries met the inclusion criteria; 1.8% (n ¼ 1807) occurred in patients with a diagnosis of placental abruption. Patients with placental abruption did not have higher cumulative incidence of renal related hospitalizations, using Kaplan–Meier survival curve. During the follow-up period patients with a history of placental abruption did not have higher rate of renal morbidity (0.2% versus 0.1%; OR 1.8; 95% CI 0.6–4.8; p ¼ 0.261). When performing a Cox proportional hazards model, adjusted for confounders such as parity and diabetes mellitus, a history of placental abruption was not associated with renal related hospitalizations (adjusted HR, 1.6; 95% CI, 0.6–4.2; p ¼ 0.381). Conclusion: Placental abruption, even though considered a part of the ‘‘placental syndrome’’ with possible vascular etiology, is not a risk factor for long-term maternal renal complications.
Obstetric complication, placental abruption, renal morbidity
Introduction Chronic kidney disease (CKD) is a worldwide public health problem. In the United States, there is a rising incidence of kidney failure, with poor outcomes and high costs [1]. Incidence of CKD varies because of differences in underlying disease rates and availability of government-sponsored treatment. Incidence is now reported as high as 200 cases per million per year in many countries [2,3]. Early stages of disease are often asymptomatic, detected during the assessment of comorbid disorders, and can be reversible. Rapidly progressive disease can lead to kidney failure within months; however, most cases evolve over decades and some patients do not progress during many years of follow-up [4]. Many patients with CKD are detected only shortly before the onset of symptomatic kidney failure, when there are few opportunities to prevent adverse outcomes [4–6]. Earlier detection allows more time for evaluation and treatment, but would require explicit testing strategies for asymptomatic
Address for correspondence: Eyal Sheiner, MD, PhD, Department of Obstetrics and Gynecology, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, POB 151, Beer Sheva 84101, Israel. Tel: +972-8-6400111. E-mail: [email protected]
History Received 31 July 2014 Revised 10 September 2014 Accepted 16 September 2014 Published online 9 October 2014
individuals at increased risk [4]. One condition that may predispose to early death in patients with CKD is vascular disease, common in CKD and a risk factor for both further renal decline and mortality [7,8]. Placental abruption is defined as the partial or complete separation of an implanted placenta from the uterine wall before delivery of the fetus [9,10]. It complicates roughly 1 in 100–200 (0.5–1%) pregnancies [9,11,12]. Chronic processes associated with vascular dysfunction, such as preeclampsia, preterm delivery, and fetal growth restrictions [9,13] are strongly association with placental abruption [9,13,14]. These pregnancy complications seem to share some common mechanisms, including diseased spiral arteries, placental ischemia and endothelial dysfunction [9,15,16]. The clustering and shared predisposing factors of these conditions have led to the conception of a ‘‘placentaassociated syndrome’’ [13,14,17]. In recent years several studies have demonstrated a link between common pregnancy complications and future risk for cardiovascular disease. These studies have demonstrated that pregnancy complications such as gestational diabetes mellitus, preeclampsia and preterm delivery are significant and independent risk factors for long-term maternal cardiovascular morbidity and related hospitalizations [18–20].
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Pregnancy is considered a physiological stress test for the pregnant woman and therefore serves as a window of opportunity for physicians to evaluate risk factors for future maternal morbidity. Since vascular pathology is central etiology for both kidney disease and placental abruption as part of the ‘‘placental syndrome’’. The aim of the study was to investigate whether women with a history of one or more pregnancies complicated by placental abruption are at higher risk of developing CKD later in life.
Materials and methods
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Setting The study was conducted at the Soroka University Medical Center, the sole hospital of the Negev, the southern region of Israel, serving the entire population in this region. Thus, the study is based on a non-selective population data. The Institutional Review Board (in accordance with the Helsinki declaration) approved the study. Study population The study population was composed of all the patients who delivered between the years 1988 and 2012; the follow-up period for renal-related hospitalizations was until 2012. Patients with multiple pregnancies, with known renal disease before or during the index pregnancy and with known congenital renal malformations were excluded from the study. Study design A population-based retrospective cohort study was conducted. The exposure was a history of diagnosis of placental abruption. Patients who for the entire period of follow up were not diagnosed with placental abruption comprised the comparison group. A retrospective follow-up of hospitalizations due to renal morbidity up to 24 years after the index birth was preformed. The exact ICD codes for each sub type of renal morbidity are presented in the Appendix. Data were collected from two databases that were crosslinked and merged: the computerized perinatal database and the hospitalization database of the Soroka University Medical Center. The perinatal database consists of information recorded directly after delivery by an obstetrician. Skilled medical secretaries routinely review the information prior to entering it into the database. Coding was performed after assessing medical prenatal care records together with the
J Matern Fetal Neonatal Med, 2015; 28(14): 1641–1646
routine hospital documents. The hospitalization data-base includes demographic information and ICD 9 codes for all medical diagnoses made during hospitalizations. Statistical analysis Statistical analysis was performed using the SPSS package 17 edition (SPSS Inc, Chicago, IL). Statistical significance was calculated using the chi square test for differences in qualitative variables and the Student t-test for differences in continuous variables. Kaplan–Meier survival curve was used to compare cumulative incidence of renal hospitalizations. Cox proportional hazards models were used to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for long-term renal hospitalizations. p value50.05 was considered statistically significant.
Results During the study period, there were 99 354 deliveries, of which 1807 (1.8%) occurred in patients with placental abruption. Table 1 summarizes characteristics of patients with and without a diagnosis of placental abruption. Women in the placental abruption group were significantly older at the index birth than women in the comparison group and had a higher parity than the comparison group. In addition, Women in the placental abruption group suffered more from post-partum anemia, preeclampsia, had higher rates of small for gestational age (SGA) neonate and had more intrauterine fetal death than women in the comparison group. There were no significant differences in subsequent longterm first hospitalization owing to renal causes during the follow-up period in patients with and without a history of placental abruption (OR, 1.8; 95% CI, 0.6–4.8; p ¼ 0.261; Table 2). Table 3 presents Cox proportional hazard models that were used to estimate the adjusted HRs and 95% CIs for the risk of hospitalizations due to renal causes. After controlling for recognized confounders associated with the risk for renal disease such diabetes mellitus, placental abruption was not independently associated an increased risk of subsequent hospitalizations due to renal causes. Figure 1 presents a Kaplan–Meier survival curve for the cumulative incidence of renal hospitalizations in both study groups (with or without a history of placental abruption).
Table 1. Characteristics of patients with and without a history of placental abruption.
Maternal age at index birth (years ± SD) Preeclampsia Diabetes mellitus (gestational and pre-gestational) Small for gestational age Intrauterine fetal death Obesity (pre- gestational BMI430 kg/m2) Parity at index birth, median (mode) Mean number of years (± SD) from index pregnancy to hospitalization
Placental abruption (n ¼ 1807)
No placental abruption (n ¼ 97 547)
p value
29.6 ± 6 11.7% 6.4% 10.2% 10.9% 0.4% 4.5 ± 3 9.0 ± 9.4
28.9 ± 6 4.9% 6.5% 4.9% 0.6% 1.0% 3.2 ± 2 12.9 ± 6.8
0.001 0.001 0.819 0.001 0.001 0.009 0.001 0.278
Placental abruption and future renal complication
DOI: 10.3109/14767058.2014.967206
Women with a history of diagnosis of placental abruption did not have a significantly higher risk of renal hospitalizations over the whole follow-up period (log rank test, p ¼ 0.204). An additional analysis was performed in order to examine a possible ‘‘dose-response’’ association between the number of past events of placental abruption and renal morbidity. In this analysis a comparison was made between patients with Table 2. Incidence of first hospitalization for all renal causes during the follow-up period in patients with and without a history of placental abruption.
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Placental No placental abruption abruption (n ¼ 1807) (n ¼ 97 547) OR 95% CI p value Total renal related hospitalizations
0.2%
0.1%
1.8
0.6–4.8
0.261
Table 3. Cox multivariable regression models for the risk of hospitalizations due to renal causes.
Placental abruption Parity Gestational diabetes mellitus
Adjusted HR
CI 95%
p value
1.6 1.2 2.5
0.6–4.2 1.15–1.28 1.6–3.8
0.381 0.001 0.001
Figure 1. The Kaplan–Meier survival curve for the cumulative incidence of mortality due to renal causes of women with and without a history of diagnosis of placental abruption.
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no history of placental abruption, patients with one event and patients with two events and more. The analysis revealed no statistically significant association between the number of past events and the risk for future renal morbidity (0.1% versus 0.2% versus 0% respectively; p ¼ 0.450).
Discussion The aim of the present population-based study was to investigate whether women with a history of one or more pregnancies complicated by placental abruption are at higher risk of developing CKD later in life. Although common pathophysiology relationship between placental abruption and CKD may exist, according to the results of our study, placental abruption is not independently associated with an increased risk of subsequent hospitalizations or to mortality due to renal causes. The premise of the study is that pregnancy is a physiological stress test for the pregnant women and as such, allows the existence of a window of opportunity for future diagnostic maternal morbidity. Testing statistical relationship is done by understanding the pathophysiological mechanisms of certain pregnancy complications that characterize long-term chronic illness. ‘‘Placenta-associated syndrome’’, which includes pregnancy complications such as preeclampsia, preterm delivery, and fetal growth restriction [20], which are known to be associated with placental abruption, share a common
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pathophysiology of a decreased vascular function. The pathology of decreased vascular function which is associated with chronic cardiovascular disease is common in CKD and a risk factor for both further renal decline and mortality [18,19]. In a recent study by Pariente et al. [20], examined 47 585 patients; of these, 653 with a history of placental abruption. Authors found that placental abruption was independently associated with long-term cardiovascular mortality (OR ¼ 6.6; 95% CI 2.3– 18.3). The key strength that offers our study is its implementation in Soroka University Medical Center, a large tertiary medical center which is a single provider of medical services to all the population of the Negev, the southern region of Israel. Thus, a patient, as long as she lives in the area, will use medical services provided by this hospital. Therefore, we were able to examine a large sample of women with placental abruption, which is an uncommon pregnancy complication, while making comparisons and drawing statistically valid conclusions. Using computerized files of information which were filled by gynecologists immediately after birth is another strength point. In this way, we minimize the possibility of missing values as well as to avoid the influence affected by recall bias. Lack of information concerning morbidity and mortality in the context of CKD outside the Soroka University Medical Center is the main limitation of our study. It can be assumed that the missing values of the relevant death from CKD which have not taken place at Soroka but outside the area of the Negev are in the same ratio in both study groups and therefore do not alter the assessment of the risk of kidney disease associated with placental abruption. In conclusion, according to the results of our study, placental abruption, even though considered a part of the ‘‘placental syndrome’’, is not a risk factor for long-term maternal renal complications. As the incidence of placental abruption has increased during the last decade, further studies are needed in order to add to existing data about the association of placental abruption and long-term chronic illness. Finding new predictors for renal and cardiovascular diseases will improve medical surveillance and outcome.
Declaration of interest The authors report no conflict of interest
References 1. Levey AS, Coresh J, Balk E, et al, for the National Kidney Foundation. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 2003;139:137–47.
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2. Levey AS, Coresh J. Chronic kidney disease. Lancet 2012;379: 165–80. 3. Kepler J. International comparisons. United States Renal Data System. 2010 Annual Data Report: atlas of chronic kidney disease and end-stage renal disease in the United States, vol 2 Atlas of ESRD. 2010. Available from: http://www.usrds.org/2010/pdf/ v2_12.pdf [last accessed 12 Jun 2011]. 4. Stevens LA, Levey AS. Current status and future perspectives for CKD testing. Am J Kidney Dis 2009;53:S17–26. 5. Kinchen K, Sadler J, Fink N, et al. The timing of specialist evaluation in chronic kidney disease and mortality. Ann Intern Med 2002;137:479–83. 6. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1S266. 7. Grams ME, Coresh J, Segev DL, et al. Vascular disease, ESRD, and death: interpreting competing risk analyses. Clin J Am Soc Nephrol 2012;7:1606–14. 8. Dru¨eke TB, Massy ZA. Atherosclerosis in CKD: Differences from the general population. Nat Rev Nephrol 2010;6:723–35. 9. Pariente G, Shoham-Vardi I, Kessous R, et al. Placental abruption as a significant risk factor for long-term cardiovascular mortality in a follow-up period of more than a decade. Paediatr Perinat Epidemiol 2014;28:32–8. 10. Sheiner E, Shoham-Vardi I, Hadar A, et al. Incidence, obstetric risk factors and pregnancy outcome of preterm placental abruption: a retrospective analysis. J Matern Fetal Neonatal Med 2002;11: 34–9. 11. Ananth CV, Savitz DA, Williams MA. Placental abruption and its association with hypertension and prolonged rupture of membranes: a methodologic review and meta-analysis. Obstet Gynecol 1996;88: 309–18. 12. Ananth CV, Savitz DA, Bowes Jr WA, Luther ER. Influence of hypertensive disorders and cigarette smoking on placental abruption and uterine bleeding during pregnancy. Br J Obstet Gynaecol 1997;104:572–8. 13. Pariente G, Wiznitzer A, Sergienko R, et al. Placental abruption: critical analysis of risk factors and perinatal outcomes. J Matern Fetal Neonatal Med 2011;24:698–702. 14. Sheiner E, Shoham-Vardi I, Hallak M, et al. Placental abruption in term pregnancies: clinical significance and obstetric risk factors. J Matern Fetal Neonatal Med 2003;13:45–9. 15. Granger JP, Alexander BT, Llinas MT, et al. Pathophysiology of hypertension during preeclampsia linking placental ischemia with endothelial dysfunction. Hypertension 2001;38:718–22. 16. Brosens JJ, Pijnenborg R, Brosens IA. The myometrial junctional zone spiral arteries in normal and abnormal pregnancies: a review of the literature. Am J Obstet Gynecol 2002;187:1416–23. 17. Pariente G, Sheiner E, Kessous R, et al. ‘‘Association between delivery of a small-for-gestational-age neonate and long-term maternal cardiovascular morbidity’’. Int J Gynecol Obstet 2013; 123.1:68–71. 18. Kessous R, Shoham-Vardi I, Pariente G, et al. An association between gestational diabetes mellitus and long-term maternal cardiovascular morbidity. Heart 2013;99:1118–21. 19. Irgens HU, Reisaeter L, Irgens LM, et al. Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study. BMJ 2001;323:1213–17. 20. Kessous R, Shoham-Vardi I, Pariente G, et al. An association between preterm delivery and long-term maternalcardiovascular morbidity. Am J Obstet Gynecol 2013;209:368.e1–8.
DOI: 10.3109/14767058.2014.967206
Placental abruption and future renal complication
Appendix Table A1
Table A1. ICD codes for each sub type of renal morbidity.
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Diagnosis Renal autotransplantation Other kidney transplantation Kidney transplantation (living) Kidney transplantation (cadaver) Chronic renal failure Hypertensive renal disease Malignant hypertensive renal disease Malignant hypertensive renal disease without renal failure Malignant hypertensive renal disease + renal failure Benign hypertensive renal disease Benign hypertensive renal disease without renal failure Benign hypertensive renal disease + renal failure Unspecified hypertensive renal disease Unspecified hypertensive renal disease without renal failure Unspecified hypertensive renal disease + renal failure Hypertensive heart and renal disease Malignant hypertensive heart and renal disease Malignant hypertensive heart 2 renal disease without congestive heart failure or renal failure Malignant hypertensive heart 2 renal disease + congestive heart failure Malignant hypertensive heart 2 renal disease + renal failure Malignant hypertensive heart 2 renal disease + congestive heart 2 renal failure Benign hypertensive heart and renal disease Benign hypertensive heart 2 renal disease without congestive heart failure or renal failure Benign hypertensive heart 2 renal disease + congestive heart failure Benign hypertensive heart 2 renal disease + renal failure Benign hypertensive heart 2 renal disease + congestive heart 2 renal failure Unspecified hypertensive heart and renal disease Unspecified hypertensive heart 2 renal disease without congestive heart failure or renal failure Unspecified hypertensive heart 2 renal disease + congestive heart failure Unspecified hypertensive heart 2 renal disease + renal failure Unspecified hypertensive heart 2 renal disease + congestive heart 2 renal failure Atherosclerosis of renal artery Malignant hypertensive heart and renal disease without mention of heart failure or renal failure Malignant hypertensive heart and renal disease with heart failure Malignant hypertensive heart and renal disease with heart and renal failure Benign hypertensive heart and renal disease without mention heart failure or renal failure Benign hypertensive heart and renal disease with heart failure Benign hypertensive heart and renal disease with heart and renal failure Unspecified hypertensive heart and renal disease without mention heart failure or renal failure Unspecified hypertensive heart and renal disease with heart failure Unspecified hypertensive heart and renal disease with heart and renal failure Atheroembolism of kidney Unspecified hypertensive kidney disease with chronic kidney disease End stage renal disease Hypertensive kidney disease Malignant hypertensive kidney disease Malignant hypertensive kidney disease without chronic kidney disease Malignant hypertensive kidney disease with chronic kidney disease Benign hypertensive kidney disease Benign hypertensive kidney disease without chronic kidney disease Benign hypertensive kidney disease with chronic kidney disease Unspecified hypertensive kidney disease Unspecified hypertensive kidney disease without chronic kidney disease Hypertensive heart and kidney disease Malignant hypertensive heart and kidney disease Malignant hypertensive heart and kidney disease without heart failure or chronic kidney disease
Code Z5561 Z5569 Z55690 Z55691 585 403 4030 40300 40301 4031 40310 40311 4039 40390 40391 404 4040 40400 40401 40402 40403 4041 40410 40411 40412 40413 4049 40490 40491 40492 40493 4401 40400 40401 40403 40410 40411 40413 40490 40491 40493 44581 40391 5856 403 4030 40300 40301 4031 40310 40311 4039 40390 404 4040 40400 (continued )
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Table A1. Continued
Diagnosis
Code
Malignant hypertensive heart and kidney disease with heart failure Malignant hypertensive heart and kidney disease with chronic kidney disease Malignant hypertensive heart and kidney disease with heart failure and chronic kidney disease Benign hypertensive heart and kidney disease Benign hypertensive heart and kidney disease without heart failure or chronic kidney disease Benign hypertensive heart and kidney disease with heart failure Benign hypertensive heart and kidney disease with chronic kidney disease Benign hypertensive heart and kidney disease with heart failure and chronic Kidney disease Unspecified hypertensive heart and kidney disease Unspecified hypertensive heart and kidney disease without heart failure or chronic kidney disease Unspecified hypertensive heart and kidney disease with heart failure Unspecified hypertensive heart and kidney disease with chronic kidney disease Unspecified hypertensive Heart and kidney disease with heart failure and chronic kidney disease Chronic kidney disease, stage I Chronic kidney disease, stage II (mild) Chronic kidney disease, stage III (moderate) Chronic kidney disease, stage IV (severe) Chronic kidney disease, stage V Malignant hypertensive kidney disease with chronic kidney disease stage V or end stage renal disease Benign hypertensive kidney disease with chronic kidney disease stage I through stage IV, or unspecified Benign hypertensive kidney disease with chronic kidney disease stage V or end stage renal disease Unspecified hypertensive kidney disease with chronic kidney disease stage I through stage IV, or unspecified Hypertensive heart and chronic kidney disease Malignant hypertensive heart and kidney disease without heart failure and with chronic kidney disease stage I through stage IV, or unspecified Malignant hypertensive heart and kidney disease with heart failure and with chronic kidney disease stage I through stage IV, or unspecified Malignant hypertensive heart and kidney disease without heart failure and with chronic kidney disease stage V or end stage renal disease Malignant hypertensive heart and kidney disease with heart failure and chronic kidney disease stage V or end stage renal disease Benign hypertensive heart and kidney disease without heart failure and with chronic kidney disease stage I through stage IV, or unspecified Benign hypertensive heart and kidney disease with heart failure and with chronic kidney disease stage I through stage IV, or unspecified Benign hypertensive heart and kidney disease without heart failure and with chronic kidney disease stage V or end stage renal disease Benign hypertensive heart and kidney disease with heart failure and chronic kidney disease stage V or end stage renal disease Unspecified hypertensive heart and kidney disease without heart failure and with chronic kidney disease stage I through stage IV, or unspecified Unspecified hypertensive heart and kidney disease with heart failure and with chronic kidney disease stage I through stage IV, or unspecified Unspecified hypertensive heart and kidney disease without heart failure and with chronic kidney disease stage V or end stage renal disease Unspecified hypertensive heart and kidney disease with heart failure and chronic kidney disease stage V or end stage renal disease
40401 40402 40403 4041 40410 40411 40412 40413 4049 40490 40491 40492 40493 5851 5852 5853 5854 5855 40301 40310 40311 40390 404 40400 40401 40402 40403 40410 40411 40412 40413 40490 40491 40492 40493
ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: http://www.tandfonline.com/loi/ijmf20
Is there an association between a history of placental abruption and long-term maternal renal complications? E. S. Arazi, R. Kessous, I. Shoham-Vardi, G. Pariente, R. Sergienko & E. Sheiner To cite this article: E. S. Arazi, R. Kessous, I. Shoham-Vardi, G. Pariente, R. Sergienko & E. Sheiner (2015) Is there an association between a history of placental abruption and long-term maternal renal complications?, The Journal of Maternal-Fetal & Neonatal Medicine, 28:14, 1641-1646, DOI: 10.3109/14767058.2014.967206 To link to this article: http://dx.doi.org/10.3109/14767058.2014.967206
Accepted author version posted online: 19 Sep 2014. Published online: 10 Oct 2014. Submit your article to this journal
Article views: 37
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ijmf20 Download by: [University of California, San Diego]
Date: 13 November 2015, At: 03:57
http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, 2015; 28(14): 1641–1646 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.967206
ORIGINAL ARTICLE
Is there an association between a history of placental abruption and long-term maternal renal complications? E. S. Arazi1, R. Kessous1, I. Shoham-Vardi2, G. Pariente1, R. Sergienko2, and E. Sheiner1
Downloaded by [University of California, San Diego] at 03:57 13 November 2015
1
Department of Obstetrics and Gynecology, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel and 2Department of Epidemiology and Health Services Evaluation, Ben-Gurion University of the Negev, Beer-Sheva, Israel Abstract
Keywords
Objective: To investigate whether patients with a history of placental abruption have an increased risk for subsequent maternal long-term morbidity. Study design: A population-based study compared the incidence of long-term renal morbidity in cohort of women with and without a history of placental abruption. Deliveries occurred during a 25-year period, with a mean follow-up duration of 11.2 years. Renal morbidity included kidney transplantation, chronic renal failure, hypertensive renal disease, etc. Results: During the study period 99 354 deliveries met the inclusion criteria; 1.8% (n ¼ 1807) occurred in patients with a diagnosis of placental abruption. Patients with placental abruption did not have higher cumulative incidence of renal related hospitalizations, using Kaplan–Meier survival curve. During the follow-up period patients with a history of placental abruption did not have higher rate of renal morbidity (0.2% versus 0.1%; OR 1.8; 95% CI 0.6–4.8; p ¼ 0.261). When performing a Cox proportional hazards model, adjusted for confounders such as parity and diabetes mellitus, a history of placental abruption was not associated with renal related hospitalizations (adjusted HR, 1.6; 95% CI, 0.6–4.2; p ¼ 0.381). Conclusion: Placental abruption, even though considered a part of the ‘‘placental syndrome’’ with possible vascular etiology, is not a risk factor for long-term maternal renal complications.
Obstetric complication, placental abruption, renal morbidity
Introduction Chronic kidney disease (CKD) is a worldwide public health problem. In the United States, there is a rising incidence of kidney failure, with poor outcomes and high costs [1]. Incidence of CKD varies because of differences in underlying disease rates and availability of government-sponsored treatment. Incidence is now reported as high as 200 cases per million per year in many countries [2,3]. Early stages of disease are often asymptomatic, detected during the assessment of comorbid disorders, and can be reversible. Rapidly progressive disease can lead to kidney failure within months; however, most cases evolve over decades and some patients do not progress during many years of follow-up [4]. Many patients with CKD are detected only shortly before the onset of symptomatic kidney failure, when there are few opportunities to prevent adverse outcomes [4–6]. Earlier detection allows more time for evaluation and treatment, but would require explicit testing strategies for asymptomatic
Address for correspondence: Eyal Sheiner, MD, PhD, Department of Obstetrics and Gynecology, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, POB 151, Beer Sheva 84101, Israel. Tel: +972-8-6400111. E-mail: [email protected]
History Received 31 July 2014 Revised 10 September 2014 Accepted 16 September 2014 Published online 9 October 2014
individuals at increased risk [4]. One condition that may predispose to early death in patients with CKD is vascular disease, common in CKD and a risk factor for both further renal decline and mortality [7,8]. Placental abruption is defined as the partial or complete separation of an implanted placenta from the uterine wall before delivery of the fetus [9,10]. It complicates roughly 1 in 100–200 (0.5–1%) pregnancies [9,11,12]. Chronic processes associated with vascular dysfunction, such as preeclampsia, preterm delivery, and fetal growth restrictions [9,13] are strongly association with placental abruption [9,13,14]. These pregnancy complications seem to share some common mechanisms, including diseased spiral arteries, placental ischemia and endothelial dysfunction [9,15,16]. The clustering and shared predisposing factors of these conditions have led to the conception of a ‘‘placentaassociated syndrome’’ [13,14,17]. In recent years several studies have demonstrated a link between common pregnancy complications and future risk for cardiovascular disease. These studies have demonstrated that pregnancy complications such as gestational diabetes mellitus, preeclampsia and preterm delivery are significant and independent risk factors for long-term maternal cardiovascular morbidity and related hospitalizations [18–20].
1642
E. S. Arazi et al.
Pregnancy is considered a physiological stress test for the pregnant woman and therefore serves as a window of opportunity for physicians to evaluate risk factors for future maternal morbidity. Since vascular pathology is central etiology for both kidney disease and placental abruption as part of the ‘‘placental syndrome’’. The aim of the study was to investigate whether women with a history of one or more pregnancies complicated by placental abruption are at higher risk of developing CKD later in life.
Materials and methods
Downloaded by [University of California, San Diego] at 03:57 13 November 2015
Setting The study was conducted at the Soroka University Medical Center, the sole hospital of the Negev, the southern region of Israel, serving the entire population in this region. Thus, the study is based on a non-selective population data. The Institutional Review Board (in accordance with the Helsinki declaration) approved the study. Study population The study population was composed of all the patients who delivered between the years 1988 and 2012; the follow-up period for renal-related hospitalizations was until 2012. Patients with multiple pregnancies, with known renal disease before or during the index pregnancy and with known congenital renal malformations were excluded from the study. Study design A population-based retrospective cohort study was conducted. The exposure was a history of diagnosis of placental abruption. Patients who for the entire period of follow up were not diagnosed with placental abruption comprised the comparison group. A retrospective follow-up of hospitalizations due to renal morbidity up to 24 years after the index birth was preformed. The exact ICD codes for each sub type of renal morbidity are presented in the Appendix. Data were collected from two databases that were crosslinked and merged: the computerized perinatal database and the hospitalization database of the Soroka University Medical Center. The perinatal database consists of information recorded directly after delivery by an obstetrician. Skilled medical secretaries routinely review the information prior to entering it into the database. Coding was performed after assessing medical prenatal care records together with the
J Matern Fetal Neonatal Med, 2015; 28(14): 1641–1646
routine hospital documents. The hospitalization data-base includes demographic information and ICD 9 codes for all medical diagnoses made during hospitalizations. Statistical analysis Statistical analysis was performed using the SPSS package 17 edition (SPSS Inc, Chicago, IL). Statistical significance was calculated using the chi square test for differences in qualitative variables and the Student t-test for differences in continuous variables. Kaplan–Meier survival curve was used to compare cumulative incidence of renal hospitalizations. Cox proportional hazards models were used to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for long-term renal hospitalizations. p value50.05 was considered statistically significant.
Results During the study period, there were 99 354 deliveries, of which 1807 (1.8%) occurred in patients with placental abruption. Table 1 summarizes characteristics of patients with and without a diagnosis of placental abruption. Women in the placental abruption group were significantly older at the index birth than women in the comparison group and had a higher parity than the comparison group. In addition, Women in the placental abruption group suffered more from post-partum anemia, preeclampsia, had higher rates of small for gestational age (SGA) neonate and had more intrauterine fetal death than women in the comparison group. There were no significant differences in subsequent longterm first hospitalization owing to renal causes during the follow-up period in patients with and without a history of placental abruption (OR, 1.8; 95% CI, 0.6–4.8; p ¼ 0.261; Table 2). Table 3 presents Cox proportional hazard models that were used to estimate the adjusted HRs and 95% CIs for the risk of hospitalizations due to renal causes. After controlling for recognized confounders associated with the risk for renal disease such diabetes mellitus, placental abruption was not independently associated an increased risk of subsequent hospitalizations due to renal causes. Figure 1 presents a Kaplan–Meier survival curve for the cumulative incidence of renal hospitalizations in both study groups (with or without a history of placental abruption).
Table 1. Characteristics of patients with and without a history of placental abruption.
Maternal age at index birth (years ± SD) Preeclampsia Diabetes mellitus (gestational and pre-gestational) Small for gestational age Intrauterine fetal death Obesity (pre- gestational BMI430 kg/m2) Parity at index birth, median (mode) Mean number of years (± SD) from index pregnancy to hospitalization
Placental abruption (n ¼ 1807)
No placental abruption (n ¼ 97 547)
p value
29.6 ± 6 11.7% 6.4% 10.2% 10.9% 0.4% 4.5 ± 3 9.0 ± 9.4
28.9 ± 6 4.9% 6.5% 4.9% 0.6% 1.0% 3.2 ± 2 12.9 ± 6.8
0.001 0.001 0.819 0.001 0.001 0.009 0.001 0.278
Placental abruption and future renal complication
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Women with a history of diagnosis of placental abruption did not have a significantly higher risk of renal hospitalizations over the whole follow-up period (log rank test, p ¼ 0.204). An additional analysis was performed in order to examine a possible ‘‘dose-response’’ association between the number of past events of placental abruption and renal morbidity. In this analysis a comparison was made between patients with Table 2. Incidence of first hospitalization for all renal causes during the follow-up period in patients with and without a history of placental abruption.
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Placental No placental abruption abruption (n ¼ 1807) (n ¼ 97 547) OR 95% CI p value Total renal related hospitalizations
0.2%
0.1%
1.8
0.6–4.8
0.261
Table 3. Cox multivariable regression models for the risk of hospitalizations due to renal causes.
Placental abruption Parity Gestational diabetes mellitus
Adjusted HR
CI 95%
p value
1.6 1.2 2.5
0.6–4.2 1.15–1.28 1.6–3.8
0.381 0.001 0.001
Figure 1. The Kaplan–Meier survival curve for the cumulative incidence of mortality due to renal causes of women with and without a history of diagnosis of placental abruption.
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no history of placental abruption, patients with one event and patients with two events and more. The analysis revealed no statistically significant association between the number of past events and the risk for future renal morbidity (0.1% versus 0.2% versus 0% respectively; p ¼ 0.450).
Discussion The aim of the present population-based study was to investigate whether women with a history of one or more pregnancies complicated by placental abruption are at higher risk of developing CKD later in life. Although common pathophysiology relationship between placental abruption and CKD may exist, according to the results of our study, placental abruption is not independently associated with an increased risk of subsequent hospitalizations or to mortality due to renal causes. The premise of the study is that pregnancy is a physiological stress test for the pregnant women and as such, allows the existence of a window of opportunity for future diagnostic maternal morbidity. Testing statistical relationship is done by understanding the pathophysiological mechanisms of certain pregnancy complications that characterize long-term chronic illness. ‘‘Placenta-associated syndrome’’, which includes pregnancy complications such as preeclampsia, preterm delivery, and fetal growth restriction [20], which are known to be associated with placental abruption, share a common
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pathophysiology of a decreased vascular function. The pathology of decreased vascular function which is associated with chronic cardiovascular disease is common in CKD and a risk factor for both further renal decline and mortality [18,19]. In a recent study by Pariente et al. [20], examined 47 585 patients; of these, 653 with a history of placental abruption. Authors found that placental abruption was independently associated with long-term cardiovascular mortality (OR ¼ 6.6; 95% CI 2.3– 18.3). The key strength that offers our study is its implementation in Soroka University Medical Center, a large tertiary medical center which is a single provider of medical services to all the population of the Negev, the southern region of Israel. Thus, a patient, as long as she lives in the area, will use medical services provided by this hospital. Therefore, we were able to examine a large sample of women with placental abruption, which is an uncommon pregnancy complication, while making comparisons and drawing statistically valid conclusions. Using computerized files of information which were filled by gynecologists immediately after birth is another strength point. In this way, we minimize the possibility of missing values as well as to avoid the influence affected by recall bias. Lack of information concerning morbidity and mortality in the context of CKD outside the Soroka University Medical Center is the main limitation of our study. It can be assumed that the missing values of the relevant death from CKD which have not taken place at Soroka but outside the area of the Negev are in the same ratio in both study groups and therefore do not alter the assessment of the risk of kidney disease associated with placental abruption. In conclusion, according to the results of our study, placental abruption, even though considered a part of the ‘‘placental syndrome’’, is not a risk factor for long-term maternal renal complications. As the incidence of placental abruption has increased during the last decade, further studies are needed in order to add to existing data about the association of placental abruption and long-term chronic illness. Finding new predictors for renal and cardiovascular diseases will improve medical surveillance and outcome.
Declaration of interest The authors report no conflict of interest
References 1. Levey AS, Coresh J, Balk E, et al, for the National Kidney Foundation. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 2003;139:137–47.
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2. Levey AS, Coresh J. Chronic kidney disease. Lancet 2012;379: 165–80. 3. Kepler J. International comparisons. United States Renal Data System. 2010 Annual Data Report: atlas of chronic kidney disease and end-stage renal disease in the United States, vol 2 Atlas of ESRD. 2010. Available from: http://www.usrds.org/2010/pdf/ v2_12.pdf [last accessed 12 Jun 2011]. 4. Stevens LA, Levey AS. Current status and future perspectives for CKD testing. Am J Kidney Dis 2009;53:S17–26. 5. Kinchen K, Sadler J, Fink N, et al. The timing of specialist evaluation in chronic kidney disease and mortality. Ann Intern Med 2002;137:479–83. 6. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1S266. 7. Grams ME, Coresh J, Segev DL, et al. Vascular disease, ESRD, and death: interpreting competing risk analyses. Clin J Am Soc Nephrol 2012;7:1606–14. 8. Dru¨eke TB, Massy ZA. Atherosclerosis in CKD: Differences from the general population. Nat Rev Nephrol 2010;6:723–35. 9. Pariente G, Shoham-Vardi I, Kessous R, et al. Placental abruption as a significant risk factor for long-term cardiovascular mortality in a follow-up period of more than a decade. Paediatr Perinat Epidemiol 2014;28:32–8. 10. Sheiner E, Shoham-Vardi I, Hadar A, et al. Incidence, obstetric risk factors and pregnancy outcome of preterm placental abruption: a retrospective analysis. J Matern Fetal Neonatal Med 2002;11: 34–9. 11. Ananth CV, Savitz DA, Williams MA. Placental abruption and its association with hypertension and prolonged rupture of membranes: a methodologic review and meta-analysis. Obstet Gynecol 1996;88: 309–18. 12. Ananth CV, Savitz DA, Bowes Jr WA, Luther ER. Influence of hypertensive disorders and cigarette smoking on placental abruption and uterine bleeding during pregnancy. Br J Obstet Gynaecol 1997;104:572–8. 13. Pariente G, Wiznitzer A, Sergienko R, et al. Placental abruption: critical analysis of risk factors and perinatal outcomes. J Matern Fetal Neonatal Med 2011;24:698–702. 14. Sheiner E, Shoham-Vardi I, Hallak M, et al. Placental abruption in term pregnancies: clinical significance and obstetric risk factors. J Matern Fetal Neonatal Med 2003;13:45–9. 15. Granger JP, Alexander BT, Llinas MT, et al. Pathophysiology of hypertension during preeclampsia linking placental ischemia with endothelial dysfunction. Hypertension 2001;38:718–22. 16. Brosens JJ, Pijnenborg R, Brosens IA. The myometrial junctional zone spiral arteries in normal and abnormal pregnancies: a review of the literature. Am J Obstet Gynecol 2002;187:1416–23. 17. Pariente G, Sheiner E, Kessous R, et al. ‘‘Association between delivery of a small-for-gestational-age neonate and long-term maternal cardiovascular morbidity’’. Int J Gynecol Obstet 2013; 123.1:68–71. 18. Kessous R, Shoham-Vardi I, Pariente G, et al. An association between gestational diabetes mellitus and long-term maternal cardiovascular morbidity. Heart 2013;99:1118–21. 19. Irgens HU, Reisaeter L, Irgens LM, et al. Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study. BMJ 2001;323:1213–17. 20. Kessous R, Shoham-Vardi I, Pariente G, et al. An association between preterm delivery and long-term maternalcardiovascular morbidity. Am J Obstet Gynecol 2013;209:368.e1–8.
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Appendix Table A1
Table A1. ICD codes for each sub type of renal morbidity.
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Diagnosis Renal autotransplantation Other kidney transplantation Kidney transplantation (living) Kidney transplantation (cadaver) Chronic renal failure Hypertensive renal disease Malignant hypertensive renal disease Malignant hypertensive renal disease without renal failure Malignant hypertensive renal disease + renal failure Benign hypertensive renal disease Benign hypertensive renal disease without renal failure Benign hypertensive renal disease + renal failure Unspecified hypertensive renal disease Unspecified hypertensive renal disease without renal failure Unspecified hypertensive renal disease + renal failure Hypertensive heart and renal disease Malignant hypertensive heart and renal disease Malignant hypertensive heart 2 renal disease without congestive heart failure or renal failure Malignant hypertensive heart 2 renal disease + congestive heart failure Malignant hypertensive heart 2 renal disease + renal failure Malignant hypertensive heart 2 renal disease + congestive heart 2 renal failure Benign hypertensive heart and renal disease Benign hypertensive heart 2 renal disease without congestive heart failure or renal failure Benign hypertensive heart 2 renal disease + congestive heart failure Benign hypertensive heart 2 renal disease + renal failure Benign hypertensive heart 2 renal disease + congestive heart 2 renal failure Unspecified hypertensive heart and renal disease Unspecified hypertensive heart 2 renal disease without congestive heart failure or renal failure Unspecified hypertensive heart 2 renal disease + congestive heart failure Unspecified hypertensive heart 2 renal disease + renal failure Unspecified hypertensive heart 2 renal disease + congestive heart 2 renal failure Atherosclerosis of renal artery Malignant hypertensive heart and renal disease without mention of heart failure or renal failure Malignant hypertensive heart and renal disease with heart failure Malignant hypertensive heart and renal disease with heart and renal failure Benign hypertensive heart and renal disease without mention heart failure or renal failure Benign hypertensive heart and renal disease with heart failure Benign hypertensive heart and renal disease with heart and renal failure Unspecified hypertensive heart and renal disease without mention heart failure or renal failure Unspecified hypertensive heart and renal disease with heart failure Unspecified hypertensive heart and renal disease with heart and renal failure Atheroembolism of kidney Unspecified hypertensive kidney disease with chronic kidney disease End stage renal disease Hypertensive kidney disease Malignant hypertensive kidney disease Malignant hypertensive kidney disease without chronic kidney disease Malignant hypertensive kidney disease with chronic kidney disease Benign hypertensive kidney disease Benign hypertensive kidney disease without chronic kidney disease Benign hypertensive kidney disease with chronic kidney disease Unspecified hypertensive kidney disease Unspecified hypertensive kidney disease without chronic kidney disease Hypertensive heart and kidney disease Malignant hypertensive heart and kidney disease Malignant hypertensive heart and kidney disease without heart failure or chronic kidney disease
Code Z5561 Z5569 Z55690 Z55691 585 403 4030 40300 40301 4031 40310 40311 4039 40390 40391 404 4040 40400 40401 40402 40403 4041 40410 40411 40412 40413 4049 40490 40491 40492 40493 4401 40400 40401 40403 40410 40411 40413 40490 40491 40493 44581 40391 5856 403 4030 40300 40301 4031 40310 40311 4039 40390 404 4040 40400 (continued )
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Table A1. Continued
Diagnosis
Code
Malignant hypertensive heart and kidney disease with heart failure Malignant hypertensive heart and kidney disease with chronic kidney disease Malignant hypertensive heart and kidney disease with heart failure and chronic kidney disease Benign hypertensive heart and kidney disease Benign hypertensive heart and kidney disease without heart failure or chronic kidney disease Benign hypertensive heart and kidney disease with heart failure Benign hypertensive heart and kidney disease with chronic kidney disease Benign hypertensive heart and kidney disease with heart failure and chronic Kidney disease Unspecified hypertensive heart and kidney disease Unspecified hypertensive heart and kidney disease without heart failure or chronic kidney disease Unspecified hypertensive heart and kidney disease with heart failure Unspecified hypertensive heart and kidney disease with chronic kidney disease Unspecified hypertensive Heart and kidney disease with heart failure and chronic kidney disease Chronic kidney disease, stage I Chronic kidney disease, stage II (mild) Chronic kidney disease, stage III (moderate) Chronic kidney disease, stage IV (severe) Chronic kidney disease, stage V Malignant hypertensive kidney disease with chronic kidney disease stage V or end stage renal disease Benign hypertensive kidney disease with chronic kidney disease stage I through stage IV, or unspecified Benign hypertensive kidney disease with chronic kidney disease stage V or end stage renal disease Unspecified hypertensive kidney disease with chronic kidney disease stage I through stage IV, or unspecified Hypertensive heart and chronic kidney disease Malignant hypertensive heart and kidney disease without heart failure and with chronic kidney disease stage I through stage IV, or unspecified Malignant hypertensive heart and kidney disease with heart failure and with chronic kidney disease stage I through stage IV, or unspecified Malignant hypertensive heart and kidney disease without heart failure and with chronic kidney disease stage V or end stage renal disease Malignant hypertensive heart and kidney disease with heart failure and chronic kidney disease stage V or end stage renal disease Benign hypertensive heart and kidney disease without heart failure and with chronic kidney disease stage I through stage IV, or unspecified Benign hypertensive heart and kidney disease with heart failure and with chronic kidney disease stage I through stage IV, or unspecified Benign hypertensive heart and kidney disease without heart failure and with chronic kidney disease stage V or end stage renal disease Benign hypertensive heart and kidney disease with heart failure and chronic kidney disease stage V or end stage renal disease Unspecified hypertensive heart and kidney disease without heart failure and with chronic kidney disease stage I through stage IV, or unspecified Unspecified hypertensive heart and kidney disease with heart failure and with chronic kidney disease stage I through stage IV, or unspecified Unspecified hypertensive heart and kidney disease without heart failure and with chronic kidney disease stage V or end stage renal disease Unspecified hypertensive heart and kidney disease with heart failure and chronic kidney disease stage V or end stage renal disease
40401 40402 40403 4041 40410 40411 40412 40413 4049 40490 40491 40492 40493 5851 5852 5853 5854 5855 40301 40310 40311 40390 404 40400 40401 40402 40403 40410 40411 40412 40413 40490 40491 40492 40493
