Retrospective analysis of the preeclampsia cases delivered in our clinic between 2013 and 2017

Objective

The aim of our study is to analyze and compare obstetric, maternal and fetal outcomes of the cases who delivered with the diagnoses of early-onset and late-onset preeclampsia.

Methods

The data of 149 patients with preeclampsia who delivered between January 2013 and August 2017 were collected and analyzed at Derince Training and Research Hospital. Of the cases, 65 were established with the diagnosis of early-onset preeclampsia and 84 were established with the diagnosis of late-onset preeclampsia. The demographic characteristics, biochemical changes, and perinatal, maternal and obstetric outcomes of both groups were compared.

Results

Between the patient groups with early-onset and late-onset preeclampsia, there was no statistically significant difference in terms of age, gravida, parity, systolic and diastolic blood pressures, laboratory values (liver function tests, hemogram, thrombocyte count), and delivery types (p>0.05). There was statistically significant difference between serum creatinine values (p=0.045). There was statistically significant difference between two groups against early-onset preeclampsia in terms of newborn weight, low birth weight infant, newborn's need for intensive care, maternal complication and intrauterine death (p<0.001).

Conclusion

Our data show that the rates of perinatal and maternal complications are higher in the patients with early-onset preeclampsia. We believe that using new predictive biomarkers is necessary for early diagnosis and labor decision in women with preeclampsia diagnosis. Considering the genetic factors and racial and ethnic differences, multi-centered studies are needed to evaluate preeclampsia-related maternal and fetal complications.

Keywords

Preeclampsia, early-onset preeclampsia, late-onset preeclampsia, maternal outcomes, newborn outcomes

Introduction

Preeclampsia is a gestational disease affecting about 5–10% of pregnant women and increasing the rates of maternal and fetal mortality significantly.[1] Hypertensive disorders are responsible for 14% of maternal mortality rates in the world.[2] Due to the insufficient access to antenatal care services in the underdeveloped and developing countries, mortality rate related with preeclampsia and its complications increases much more.[3]
Measuring blood pressure during prenatal period, the early gestational period or second trimester is quite important to establish the diagnosis of preeclampsia which may develop during pregnancy.[4] High blood pressure and the presence of proteinuria which are found after 20 weeks of gestation in a pregnant woman used to be known normotensive is defined as preeclampsia. However, the presence of proteinuria is not always a must for preeclampsia diagnosis. In the lack of proteinuria, preeclampsia finding can also be established in cases where systemic findings (renal failure, liver dysfunction, pulmonary edema, cerebral and visual symptoms, hemolysis and the presence of thrombocytopenia) accompany hypertension.[5]
The week of gestation when preeclampsia is identified is the most important clinical variable to predict both maternal and prenatal outcomes. When preeclampsia develops before 32 weeks of gestation, it causes 20 times higher maternal mortality than the term pregnancy.[6] Increased maternal and fetal risks observed in the early-onset preeclampsia support the opinion that the pathophysiology of early-onset preeclampsia is different.[7] It has been also reported that the risks of developing cardiovascular disease in the further lives of women who were diagnosed with early-onset preeclampsia are increased.[8] Moreover, early-onset preeclampsia also affects fetal prognosis negatively. Placental dysfunction, intrauterine growth retardation, abnormal uterine and umbilical artery Doppler evaluation, low birth weight and multiple organ dysfunctions may be concurrent with fetal outcomes associated with prenatal death.[9] Late-onset preeclampsia is considered mainly as a maternal disorder. It is frequently associated with a normal placenta, normal fetal development, normal uterine and umbilical artery Doppler evaluation, normal birth weight and more positive maternal and neonatal outcomes.[9,10] Therefore, the opinion that early-onset preeclampsia mostly has more severe clinical course gains importance.[11]
In pregnancies complicated with preeclampsia, many life-threatening maternal complications from ablatio placentae, intracranial bleeding, liver failure, kidney failure, and disseminated intravascular coagulation to death can be seen.[12] As it is a progressive disease, the only treatment option is to complete the pregnancy by delivery in order to prevent fetal and maternal complications. Delivery timing and delivery type should be determined according to the gestational age, preeclampsia severity, and maternal and fetal well-being.[5,10,13]
The aim of this study is to compare patients who were diagnosed with early-onset and late-onset preeclampsia and delivered in our clinic according to their biochemical changes and prenatal and maternal outcomes.

Methods

The medical records of 223 patients who were diagnosed with preeclampsia and delivered in the Clinic of Gynecology and Obstetrics of Derince Training and Research Hospital, Health Sciences University between 2013 and 2018 were analyzed retrospectively. The medical records of 149 patients whose files were accessed from hospital database and patient files were analyzed and 13 of them were excluded from the study due to their concomitant diseases (diabetes, autoimmune disease, chronic hypertension).
The diagnosis of preeclampsia was established according to the criteria of ACOG (American College of Obstetricians and Gynecologist).[5] According to these criteria, (1) the presence of 140–159 mmHg or higher persistent systolic blood pressure (BP) or 90–109 mmHg or higher diastolic BP which develops after 20 weeks of gestation in a woman who previously had normal blood pressure, (2) concomitant systemic findings (proteinuria >300 mg/24-hour, thrombocytes <100,000/ dL, at least 2 times increase of transaminase level, creatinine value >1.1 mg/dL, presence of pulmonary edema, presence of cerebral or visual symptoms) in addition to blood pressure of 160/100 mmHg or above with an interval of 15 minutes, and (3) measuring blood pressure ≥160/100 mmHg with 4-hour interval in addition to minimum one systemic finding were considered preeclampsia. When it was found that hemolysis, lactate dehydrogenase was >600 IU/L, total bilirubin was >1.2 mg/dl, aspartate aminotransferase (AST) was >70 IU/L, and thrombocytes were <100,000 cell/mm3 in a patient with preeclampsia, the diagnosis of HELLP syndrome was established. The cases found to have new-onset grand mal seizures were considered eclampsia.
All blood pressure measurements were carried out by a sleeve sphygmomanometer at sitting position as the arm is on heart level.
Although the presence of proteinuria is not among the definitive diagnosis criteria of preeclampsia, we included proteinuria values of our patients in our study. The protein amount in 24-hour urine obtained from patients was measured with precipitation method by using trichloroacetic acid (TCA) (the collected urine amount was measured and 5 ml of it was put in graduated conic tube; by adding 2.5 ml TCA, it was centrifuged at 3500–4000 rpm; the precipitation level obtained was measured and its equivalent value in nomogram was recorded as g/l). Presence of protein more than 300 mg/L in 24-hour urine was considered proteinuria. The presence of proteinuria was evaluated by dipstick test in patients who admitted under emergency conditions and taken to delivery room for labor. In dipstick proteinuria test, the presence of protein ≥1+ was considered proteinuria.
Week of gestation was determined according to crown-rump length (CRL) measurement performed between 8 and 16 weeks of gestation.[10] The patients were categorized in 2 groups according to the week of gestation when preeclampsia developed. The preeclampsia developed before 34 weeks of gestation was defined early-onset, and it was defined late-onset when it developed after 34 weeks of gestation.[14]
Of the pregnant women in both groups, the weeks of gestation when the patients were diagnosed with preeclampsia, their blood pressure measurements when they were diagnosed with preeclampsia, weeks of gestation at labor, delivery types, birth weights, fetal (low birth weight, newborn’s need for intensive care unit, intrauterine death) and maternal (eclampsia, detachment, HELLP syndrome) complications were recorded. The data of the patients on hemogram, routine biochemistry (liver function tests, kidney function tests, total), and the presence of proteinuria which were obtained by file screening were recorded.
All data obtained from the study were analyzed by using “Statistical Packages for the Social Science” (SPSS) 11.5 (SPSS Inc., Chicago, IL, USA) statistics software on Windows operating system. After definitive statistical analyses (frequency, percentage distribution, mean±standard deviation), the conformity of variables to normal distribution was evaluated by Shapiro-Wilks test. Pearson’s chi-squared test was used for the comparisons of categorical variables. p<0.05 was considered statistically significant.

Results

The demographic characteristics and laboratory findings of the patients in the early-onset preeclampsia and late-onset preeclampsia groups included in the study are shown in Table 1. Fifty-one (78.5%) patients diagnosed with early-onset preeclampsia and 84 (100%) patients diagnosed with late-onset preeclampsia had proteinuria (p<0.001). Compared to the infants of pregnant women diagnosed with late-onset preeclampsia, the infants of pregnant women diagnosed with early-onset preeclampsia had higher rates of newborn's need for intensive care and intrauterine death, which was statistically significant. Similarly, maternal complication rate was higher in the group diagnosed with early-onset preeclampsia (Table 2).

Discussion

Preeclampsia is a progressive disease specific to the last half of pregnancy. Examining symptoms and findings specific to the disease during routine antenatal visits is important in terms of preventing maternal and fetal mortality and morbidity.[5]
In our study, we defined the preeclampsia developing before 34 weeks of gestation as “early-onset” while the preeclampsia developing after 34 weeks of gestation as “late-onset”. While some studies have used this classification,[10,11,15] some studies defined early-onset preeclampsia when it developed before 37 weeks of gestation.[16]
In our study, 43.6% (n=65) of preeclampsia patients were early-onset and 56.4% (n=85) of them were late-onset. The studies performed in the past years support the idea that early-onset preeclampsia and late-onset preeclampsia may be different diseases associated with different biochemical markers, risk factors, clinical characteristics and hemodynamic conditions.[17,18] Although the etiology of preeclampsia has not been fully clarified yet, one of the most prominent hypotheses is placental angiogenesis and uteroplacental failure associated with the incomplete placental development.[19] In the early-onset preeclampsia, abnormal placentation and insufficient remodeling in spiral artery are seen specifically; however, these conditions are rarely seen in late-onset preeclampsia.[20]
The previous studies showed that early-onset preeclampsia is significantly associated with high rates of perinatal mortality and morbidity.[20] Quaker et al. found that stillbirth rate decreases as the week of gestation progresses. In their studies, the authors reported that the rate of stillbirth associated with preeclampsia is 0.52%, and that the risk of fetal death associated with preeclampsia starts when preeclampsia becomes clear clinically.[21] In the study of Kumru et al., the authors found the rate of intrauterine death 6.1% in severe preeclampsia cases.[22] Consistent with the literature, we observed intrauterine death in 4 (6.2%) of the cases with early-onset preeclampsia in our study while there was no stillbirth in late-onset preeclampsia group.
Some investigators argue that early-onset preeclampsia is a part of severe preeclampsia.[21] In our study, we found significantly high rate of maternal complication in the early-onset preeclampsia group. We found ablatio placentae and eclampsia in 3 (4.6%) of the patients in the early-onset preeclampsia group, but they were uncontrollable complications as these patients were not being followed up. While there was no difference between the incidences of early-onset and late-onset preeclampsia complicated with HELLP syndrome,[23] we found HELLP syndrome only in 1 patient in the late-onset preeclampsia group in our study.
In 2014, Doddamani et al. reported in their study that perinatal mortality rate increase in direct proportion to the severity of preeclampsia and that the newborn's need for intensive care is 26.6%.[24] In terms of the newborn's need for intensive care unit, we found this rate 38.5% in the cases with early-onset preeclampsia and 4.8% in the cases with late-onset preeclampsia. We believe that the high rate of newborn's need for intensive care in the early-onset preeclampsia group according to the literature is associated with the high rate of cesarean section.
A retrospective cohort study conducted in 2002 reported that birth weights of the newborns of mothers diagnosed with preeclampsia were lower compared to the weeks of gestation in a statistically significant level, but the birth weights of the newborns delivered by preeclamptic pregnant women at 37 weeks of gestation were within normal range.[20] In our study, 17% of the pregnant women with early-onset preeclampsia and 10% of the pregnant women with late-onset preeclampsia delivered newborns with low birth weights. However, these results did not reach a statistically significant level (p<0.270). The literature does not support this result of our study. We think that this result depends on the impacts of ethnic, environmental and genetic factors on newborn birth weights and the low number of patients included in our study group.
It is known that the only treatment option of preeclampsia is to complete the pregnancy by delivery. However, if the labor is completed on time and delayed, maternal (cerebral hemorrhage, hepatic rupture, kidney failure, pulmonary edema, DIC, ablatio placentae, etc.) and fetal complications (intrauterine growth retardation, intrauterine death, etc.) become inevitable.[5,10] NICE clinical guidelines[25] and ACOG[5] recommend conservative treatment by close fetal and maternal monitorization if fetal and maternal conditions are stable during early weeks of gestation in order to avoid fetal sequels associated with premature labor. However, conservative treatment may also cause complications such as maternal mortality and intrauterine death since the preeclampsia is a progressive disease. In our study, we did not find maternal mortality in either group despite the increased newborn’s need for intensive care due to the increased rate of premature labor.
There is different information in the literature about delivery types of preeclampsia cases. Zhang et al. carried out labors by cesarean section in more than half of their patients with preeclampsia and eclampsia.[12] Kumru et al.[22] reported labor by cesarean section in 51.5% of the severe preeclamptic cases. In our study, cesarean section rate is quite higher than the rates reported in the literature. The primary cesarean section rate in study was 78.1% in the early-onset preeclampsia group and 70.2% in the late-onset preeclampsia group. We believe that the patients that we followed up due to preeclampsia should be reconsidered in terms of delivery type in the light of the literature.
It is known that preeclampsia is a multisystemic disease which can develop with liver and kidney dysfunctions. During gestation, blood urea nitrogen (BUN), creatinine and uric acid levels are reliable markers to evaluate the glomerular filtration rate. The studies performed in the past years showed that blood urea nitrogen, creatinine and uric acid are significantly higher in pregnant women who were diagnosed with early-onset and late-onset preeclampsia presenting with severe hypertension than the healthy pregnant women. However, there is no statistically significant difference in the renal functions between the early-onset and late-onset preeclampsia patients.[26] In our study, we found creatinine levels statistically higher in the early-onset preeclampsia group (p=0.045). We think that this statistical difference in the creatinine levels is caused by higher maternal complication rates in the early-onset preeclampsia group. However, new biomarkers are needed to predict the early diagnosis of preeclampsia and to guide us for labor decision.

Conclusion

In our study, we showed that perinatal outcomes (intrauterine death, newborn’s need for intensive care) and maternal complications (ablatio placentae, eclampsia) are higher in the patients with early-onset preeclampsia. We believe that the patients should be followed up closely in primary and secondary hospitals in terms of early diagnosis in order to decrease the rates of maternal complications associated with preeclampsia much more. In order to decrease the newborn’s need for intensive care that we found higher rates in our study compared to the literature and to prevent associated fetal complications, hospitalizing patients and following up closely, determining time and type of delivery according to the progression will contribute to the decrease of maternal and fetal mortality rates.

References

1. Wallis AB, Saftlas AF, Hsia J, Atrash HK. Secular trends in the rates of preeclampsia, eclampsia, and gestational hypertension, United States, 1987–2004. Am J Hypertens 2008;21:521–6. [PubMed] [CrossRef] 


2. Say L, Chou D, Gemmill A, Tunçalp Ö, Moller AN, Daniels J; et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health 2014;2:e323–33. [PubMed] [CrossRef] 


3. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol 2009;33:130–7. [PubMed] [CrossRef] 


4. Beksaç MS. Preeklampsinin önceden belirlenmesi ve önlenmesi. Perinatoloji Dergisi 1993;1:31–4. 


5. Roberts JM, August PA, Bakris G, Barton JR, Bernstein IM, Druzin M, et al.; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Washington, DC: The American College of Obstetricians and Gynecologists; 2013. 


6. MacKay AP, Berg CJ, Atrash HK. Pregnancy-related mortality from preeclampsia and eclampsia. Obstet Gynecol 2001;97:533–8. [PubMed] 


7. Dissanayake VH, Samarasinghe HD, Morgan L, Jayasekara RW, Seneviratne HR, Broughton Pipkin F. Morbidity and mortality associated with pre-eclampsia at two tertiary care hospitals in Sri Lanka. J Obstet Gynaecol Res 2007;33:56–62. [PubMed] [CrossRef] 


8. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ 2007;335(7627):974. [PubMed] [CrossRef] 


9. Obed S, Patience A. Birth weight and ponderal index in pre-eclampsia: a comparative study. Ghana Med J 2006;40:8–13. [PubMed] 


10. Heard AR, Dekker GA, Chan A, Jacobs DJ, Vreeburg SA, Priest KR. Hypertension during pregnancy in South Australia, part 1: pregnancy outcomes. Aust N Z J Obstet Gynaecol 2004;44:404–9. [PubMed] [CrossRef] 


11. Von Dadelszen P, Magee LA, Roberts JM. Subclassification of preeclampsia. Hypertens Pregnancy 2003;22:143–8. [PubMed] [CrossRef] 


12. Zhang J, Meikle S, Trumble A. Severe maternal morbidity associated with hypertensive disorders in pregnancy in the United States. Hypertens Pregnancy 2003;22:203–12. [PubMed] [CrossRef] 


13. Vreeburg SA, Jacobs DJ, Dekker GA, Heard AR, Priest KR, Chan A. Hypertension during pregnancy in South Australia, part 2: risk factors for adverse maternal and / or perinatal outcome – results of multivariable analysis. Aust N Z J Obstet Gynaecol 2004;44:410–8. [PubMed] [CrossRef] 


14. Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 2004;350:672–83. [PubMed] [CrossRef] 


15. Tranquilli AL, Dekker G, Magee L, Roberts J, Sibai BM, Steyn W, et al. The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP. Pregnancy Hypertens 2014;4:97–104. [PubMed] [CrossRef] 


16. Wikström AK, Larsson A, Eriksson UJ, Nash P, Olovsson M. Early postpartum changes in circulating pro- and anti-angiogenic factors in early-onset and late-onset pre-eclampsia. Acta Obstet Gynecol Scand 2008;87:146–53. [PubMed] [CrossRef] 


17. Raymond D, Peterson E. A critical review of early-onset and late-onset preeclampsia. Obstet Gynecol Surv 2011;66:497–506. [PubMed] [CrossRef] 


18. Sibai BM, Mercer B, Sarinoglu C. Severe preeclampsia in the second trimester: recurrence risk and long-term prognosis. Am J Obs Gynecol 1991;165:1408–12. [PubMed] [CrossRef] 


19. Roberts JM, Escudero C. The placenta in preeclampsia. Pregnancy Hypertens 2012;2:72–83. [PubMed] [CrossRef] 


20. Lisonkova S, Joseph KS. Incidence of preeclampsia: risk factors and outcomes associated with early- versus late-onset disease. Am J Obs Gynecol 2013;209:544.e1–544.e12. [PubMed] [CrossRef] 


21. Harmon QE, Huang L, Umbach DM, Klungsøyr K, Engel SM, Magnus P, et al. Risk of fetal death with preeclampsia. Obstet Gynecol 2015;125:628–35. [PubMed] [CrossRef] 


22. Kumru P, Kartal ÖP, Köse G, Aka N, Büyükoğlu B. Preeklampsi, eklampsi ve HELLP sendromu olgularımızın değerlendirilmesi. Türkiye Klinikleri Journal of Clinical Obstetrics and Gynecology 2005;15:72–80. 


23. Yildirim G, Gungorduk K, Gul A, Asicioglu O, Sudolmus S, Gungorduk OC, et al. HELLP syndrome: 8 years of experience from a tertiary referral center in western Turkey. Hypertens Pregnancy 2012;31:316–26. [PubMed] [CrossRef] 


24. Doddamani GB, Doddamani UG. Prenatal outcome in pre-eclampsia: a prospective study. Scholars Journal of Applied Medical Sciences 2014;2:291–3. 


25. National Collaborating Centre for Women’s and Children’s Health (UK). Hypertension in pregnancy: the management of hypertensive disorders during pregnancy. NICE Clinical Guidelines, No. 107. London: RCOG Press; 2010. Available from: https://www.ncbi.nlm.nih.gov/books/ NBK62652/ [PubMed]


26. Li XL, Guo PL, Xue Y, Gou WL, Tong M, Chen Q. An analysis of the differences between early and late preeclampsia with severe hypertension. Pregnancy Hypertens 2016;6:47–52. [PubMed] [CrossRef] 

	File/Dsecription
	Table 1. Comparison of two groups in terms of demographic data, blood pressure measurements and laboratory parameters.
	Table 2. Labor characteristics and maternal and fetal outcomes of two groups.