Research Article - Biomedical Research (2017) Volume 28, Issue 3

Potential risk factor of pre-eclampsia among healthy Chinese women: a retrospective case control study

¹Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan 430060, PR China

²Department of Gynecology and Obstetrics, Wuhan Medical & HealthCare Center for Women and Children (Wuhan Children’s Hospital Wuhan Women and Children Care Hospital), Wuhan 430016, PR China

³Department of Gynecology and Obstetrics, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, PR China

⁴Department of Gynecology and Obstetrics, Second People's Hospital of Huanggang City, Huanggang 436315, PR China

*Corresponding Author:

Yang Jing
Department of Gynecology and Obstetrics
Renmin Hospital of Wuhan University, PR China

Accepted date: July 29, 2016

Abstract

Objective: To identify predictive factors which helps in screening the healthy Chinese pregnant women who were at high risk of developing Pre-Eclampsia (PE).

Materials and methods: We have reviewed the medical records of healthy Chinese pregnant women with single gestation and had given birth to baby at department Ggynecology and obstetrics, Wuhan Medical & HealthCare Center for Women and Children (Wuhan Children’s Hospital Wuhan Women and Children Care Hospital) , china between January 2006 and July 2015.We reviewed the medical records of each healthy pregnant woman who were diagnosed pre-eclamptic before labor pain (case), and not diagnosed pre-eclamptic (control), and data were analysed using univariate analysis.

Result: Medical records of 32, 000 pregnant women who were admitted during January 2006 to July 2015 in our hospital were studied. Of total cases, 853 (3%) had PE. Abnormal perinatal outcome was significantly higher in women with PE compared to control women; this indicates that the PE is responsible for adverse maternal and foetal outcome. Incidence of gestational diabetes mellitus (GDM), urinary infection was meaningfully greater among women with PE than women with no PE. Family history of diabetes and hypertension was significantly higher in women with PE when compared with control group. We also observed that the stress score was significantly higher in women with PE than control.

Conclusion: We suggest GDM, family history of DM/high blood pressure; urinary tract infection, fibroids and psychological stress during pregnancy are key predictors of PE among Chinese pregnant women. These prognostic factors help in screening the pregnant women who were at high risk of developing PE.

Keywords

Pre-eclampsia, Pregnancy, Predictive factors, Diabetes, Hypertension.

Introduction

Pre-Eclampsia (PE) is one of most common cause of complications in pregnant women leading to maternal morbidity and mortality [1], and it is the second most common cause of abnormal pregnancy outcome [2]. Pre-eclampsia is commonly observed during second trimester of pregnancy, with blood pressure greater than 140/90 mmHg and presence of albumin in urine (usually more than 300 mg in 24 hour) [3]. The prevalence of PE ranges from 4% to 7% among pregnant women [4]. World Health Organization reports suggested that approximately 70,000 cases of maternal morbidity and mortality occurred due to PE every year worldwide [1]. In women with mild to moderate PE, generally no symptoms reported. In pregnant women with severe PE often experienced increased blood pressure, headache, and proteinuria [5].

The key risk factor of PE includes ethnicity, family history, weight, high blood glucose level, age of women before and after pregnancy, previous history of renal disorder, hypertension and auto-immune disease [6]. Since etiology of PE is remain unclear in spite of several efforts to find the potential reasons, thus there was no established and effective methods to prevent the PE. Therefore, identification of potential risk factor in development of PE helps to prevent incidence of PE. The prevalence of PE among Asian patients was found lower compared to white pregnant women [7,8]. The prevalence and risk factor of PE in healthy Chinese pregnant was not evaluated earlier. Therefore, we designed this study to evaluate prevalence and risk factor of PE among healthy Chinese pregnant women. We also evaluated the relationship between PE and family history of high blood pressure and GDM. The objective of present study was to identify predictive factors that can be used in screening the pregnant women who are at high risk of developing PE, this may help in reducing the incidence of PE related morbidity and mortality in pregnant women.

Materials and Methods

We reviewed the medical records of healthy Chinese pregnant women with single gestation and had given birth to baby at Department of Gynecology and Obstetrics, Wuhan Medical & HealthCare Center for Women and Children (Wuhan Children’s Hospital Wuhan Women and Children Care Hospital) from January 2006 to July 2015We used computerized database of maternal and child health care center to collect required data to fulfil the objective of our study. We have excluded the medical records of pregnant women who had diabetes, history of chronic hypertension and/or had hypertension before second trimester of pregnancy and/or had multiple gestations. Also medical records of patients who had BMI of 30 kg/m² or more (obese patients) have been excluded from analysis. Institutional ethics committee approval was obtained from Wuhan Medical & HealthCare Center for Women and Children (Wuhan Children’s Hospital Wuhan Women and Children Care Hospital). Since, this was a retrospective, observational chart review study, and none of patients whose medical records reviewed were contacted, the requirement for obtaining formal informed consent was waived by ethics committee.

The information related to outcome of pregnancy from labor to birth including postpartum interview were captured in medical records of each pregnant woman. We reviewed the medical records of each healthy pregnant woman who were diagnosed pre-eclamptic before labor pain (case), and who were not diagnosed pre-eclamptic (control). The pregnant women who were not diagnosed hypertensive before 2^nd trimester, but their blood pressure was higher than 140/90 mmHg in last trimester with urine albumin level of more than 300 mg were in PE cases group, those who had no higher blood pressure and urine albumin level were considered in control group.

The below risk factors were evaluated in light of potential covariates: Age (≤ 18 year; 19-34 year and ≥ 35 year); smoking status (Smoker; non-smoker); GDM, anxiety during pregnancy; years of schooling; body weight; overweight (25-29 kg/m²); urinary tract infection during pregnancy; Noncancerous growths of the uterus (fibroids); past experience of pre-eclamptic; family history of hypertension and diabetes; blood type; conception technique; gender of born baby. The general protocol/policy of hospital, each pregnant women were asked to rate their stress level during pregnancy using Perceived Stress Scale (PSS), which contain 10 questionnaire, each question score range from 0 to 4; total score was range from 0 to 40 where 0 indicates no stress and, higher score of PSS indicates greater stress during pregnancy. Perinatal outcome related data such as baby weight of less than 1.5 kg; Apgar score (1-min and 5 min of score less than 7); pre-term delivery; kind of delivery (normal or caesarean); requirement of neonatal intensive care unit transfer; fatal/neonatal death; postpartum haemorrhage and abruptio placentae were also captured from medical records of all pregnant women.

Data from each patient was coded and analysed using Graph Pad Prism statistical analysis software (version 6.0). Quantitative variable was presented as mean ± standard deviation, and data were compared using parametric/nonparametric statistical test based number of comparison group and distribution of data, using 2 sided statistical tests. Normality test (Kolmogorov-Smirnov test or Shapiro-Wilks test) will be used to check the distribution of data of quantitative data. Categorical variables was presented as absolute number and/or percentage of subjects in each category, and were compared using Chi-square or fisher exact test based on size of data, using 2 sided statistical tests.

Result

We have reviewed medical records of 32, 000 pregnant women who had visited during January 2006 to July 2015 in our hospital. Of 32,000 cases, 853 (3%) patients had PE. The average age at the time of baby birth was higher in preeclamptic pregnant women than non-pre-eclamptic women. Similar trend was observed when pre-pregnancy weight was compared among women with PE with control. On comparing BMI, significantly higher proportion of overweight women (25-29 kg/m²) was in PE group as compared to control group. This indicates that the majority of women with PE were overweight before pregnancy as shown in Table 1. There was no statistical significant difference in terms of number of year of education was observed among both the groups (p>0.05).

Table 1. Demography and clinical characteristic of pregnant women admitted in Wuhan Medical & HealthCare Center for Women and Children (Wuhan Children’s Hospital Wuhan Women and Children Care Hospital) from January 2006 to july 2015.

Abnormal perinatal outcome such as baby weight of less than 1.5 kg and Apgar score (1 min and 5 min of score less than 7) was significantly higher in women with PE compared to control women. Moreover, proportion of pre-mature delivery was significantly higher in women with PE compared to control women. Caesarean delivery remained significantly higher in women with PE compared to control women. We also observed that the requirement of neonatal intensive care unit transfer was significantly higher in women with PE compared to control women. Incidence of postpartum haemorrhage and abortion placenta were significantly higher in women with PE as compared to control as shown in Table 2.

Table 2. Abnormal pregnancy outcome due to pre-eclampsia in pregnant women.

In PE groups, incidence of GDM was significantly higher in comparison to control group. Also incidence of urinary tract infection and fibroids was significantly higher in women with PE than women with no PE. Family history of diabetes and hypertension was significantly higher in women with PE when compared with control group. We also observed that the stress score was significantly higher in women with PE than control. No significant difference between women with PE or control was observed in respects to age of their spouse, use of condom during conception, gender of new born baby, blood group including Rh factor. Incidence of PE was significantly higher in women who were smoker than non-smoker.

Higher risk of PE was found in women with family history of diabetes and hypertension as compared to women with no family history of diabetes and hypertension as shown in Table 3. We found that the risk of PE was double in women who had family history of diabetes and hypertension when compared to women with no family history of diabetes and hypertension. We also noticed that the stress score was significantly higher in women with PE when compared women who had no PE.

Table 3. Prognostic factors for increased incidence of pre-eclampsia in pregnant women.

Discussion

This was the first largest retrospective case control study to determine the prevalence and PE risk factor among healthy Chinese pregnant women. In our study, the prevalence of PE among Chinese pregnant women was lower than Caucasians and other non-Asian pregnant women [9-14]. Lower prevalence of Chinese pregnant women was possibly attributed to body mass index, routine living including living relationship with their spouse [15]. Our study results were consistent with findings of Xiao et al. [15], which suggested that Chinese ethnicity might be accountable for lower prevalence of PE. Our study suggested that PE is comparatively infrequent among Chinese pregnant women.

Our finding showed that pregnant women with GDM were at higher risk of developing PE, GDM was associated with the subsequent development of PE. Our study showed positive relationship between PE and diabetes, and our finding was consistent with previous findings [16-27]. It has been reported that GDM is independently and significantly associated with an increased risk of PE, and even small degree of glucose imbalance lead to development of PE [19-21]. There was positive correlation between insulin resistance and diabetes mellitus with increased blood pressure; hyperinsulinaemia was known to excite the reproduction of muscle cells which thereby activate secretion of neurotransmitter namely noradrenaline and adrenaline which results in increased BP. Hyperinsulinemia also lead to renal sodium retention and associated with endothelial dysfunction. This all alterations after glucose metabolism imbalance may contribute to increased blood pressure [26,27].

Our study results showed that the pregnant women with family history of hypertension were at higher risk of developing PE; our finding is consistent with previous studies [28-30]. Our results showed positive relationship between family history of chronic hypertension and risk of PE. Our results recommended that the family history of chronic hypertension is an alternative measure for hereditary factors that may be one of cause PE [7]. Women with family history of chronic hypertension are one of the most common clinical risk makers of PE compared to the biochemical markers.

In our study, incidence of PE was significantly greater in women with higher stress score compared to women with no stress during pregnancy. Our study results showed positive association of mental stress during pregnancy and development of PE. We observed that the pregnant women with greater stress are at very high risk of developing PE. Increased incidences of PE in women with mental stress could be explained based on the facts that psychosocial strain leads to vasoconstriction and increased uterine artery resistance, which results in development of PE [31-33]. Role of stress disorder such as depression and anxiety in developing PE during pregnancy was well established [34], and positively correlated. Apart from anxiety disorders, any kind of mental stress due to uneasy environment of office and home which could results in biological alterations in pregnant women lead to complications such as PE and pre-mature labor pain [35,36]. Moreover, prenatal stress may changes maternal physiology and immune function; this may also lead to increased risk of PE [29].

Additionally, we found that the prevalence of PE was significantly higher in women with urinary tract infection and fibroids compared to women with no urinary tract infection and fibroids during pregnancy. Our study results showed association of urinary tract infection and fibroids during pregnancy and development of PE. We observed that the pregnant women with urinary tract infection and fibroids are at very high risk of developing PE. Our finding of increased incidences of PE in women with urinary tract infection and fibroids is in consistent with the previous report [37]. In the past decades, many laboratory tests has been advised to discover the potential risk of developing PE in pregnant women, however, such as lab investigations have inadequate sensitivity and costly which was difficult to afford. We suggest family history of hypertension; diabetes; gestational diabetes, and mental stress can be better screening tools to determine risk of PE in pregnancy.

The predictive factors such as gestational diabetes, mental stress are amendable and avoidable risk factor of PE, whereas family history of diabetes and hypertension even could not be modifiable, nonetheless very useful to identify the pregnant women who are at higher risk of PE and need more attention. This help in reducing the incidence of PE related morbidity and mortality in pregnant women. We encourage increasing awareness of risk factor of PE, which could lead to decrease prevalence of PE among pregnant women.

Conclusion

We suggest GDM, family history of high blood pressure and psychological stress during pregnancy is important predictors of PE among Chinese pregnant women since incidence of PE were significantly higher in pregnant women with GDM, family history of high blood pressure and increased mental stress during pregnancy. Moreover, higher incidences of PE were found in pregnant women with urinary tract infection and fibroids during pregnancy, this indicates urinary tract infection and fibroids during pregnancy are also key determinant of PE in pregnant women. These prognostic factors can be used in screening the pregnant women who were at high risk of developing PE. This finding help in reducing the incidence of PE related morbidity and mortality in pregnant women. We encourage increasing awareness of risk factor of PE, which could lead to decrease incidences of PE among pregnant women.

Acknowledgements

All authors would like to thank the subjects for their participation in this observational retrospective study.

References

1. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005; 365: 785-799.
2. Sibai BM, Ewell M, Levine RJ, Klebanoff MA, Esterlitz J, Catalano PM, Goldenberg RL, Joffe G. Risk factors associated with preeclampsia in healthy nulliparous women. The Calcium for Preeclampsia Prevention (CPEP) study group. Am J Obstet Gynecol 1997; 177:1003-1010.
3. Sutapa A, Gagandeep KW. Prevalence and risk factors for symptoms suggestive of pre-eclampsia in Indian women. J Womens Health 2014; 3: 1-9.
4. Landau R, Irion O. Recent data on the physiopathology of preeclampsia and recommendations for treatment. Rev Med Suisse 2005; 1: 292-295.
5. Duley L. Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Caribbean. Br J Obstet Gynaecol 1992; 99: 547-553.
6. Mostello D, Catlin TK, Roman L, Holcomb WL Jr, Leet T. Preeclampsia in the parous woman-who is at risk. Am J Obstet Gynecol 2002; 187: 425-429.
7. Mahomed K, Williams MA, Woelk GB, Jenkins-Woelk L, Mudzamiri S, Longstaff L. Risk factors for pre-eclampsia among Zimbabwean women-maternal arm circumference and other anthropometric measures of obesity. Paediatr Perinat Epidemiol 1998; 12: 253-262.
8. Xiao J, Shen F, Xue Q, Chen G, Zeng K. Is ethnicity a risk factor for developing preeclampsia. An analysis of the prevalence of preeclampsia in China. J Hum Hypertens 2014; 28: 694-698.
9. Sibai BM, Gordon T, Thom E, Caritis SN, Klebanoff M, McNellis D. Risk factors for preeclampsia in healthy nulliparous women: a prospective multicenter study. The national institute of child health and human development network of maternal foetal medicine units. Am J Obstet Gynecol 1995; 172: 642-648.
10. Sibai BM, Ewell M, Levine RJ, Klebanoff MA, Esterlitz J, Catalano PM. Risk factors associated with preeclampsia in healthy nulliparous women. The Calcium for Preeclampsia Prevention CPEP. Study Group. Am J Obstet Gynecol 1997; 177: 1003-1010.
11. Ros HS, Cnattingius S, Lipworth L. Comparison of risk factors for preeclampsia and gestational hypertension in a population-based cohort study. Am J Epidemiol 1998; 147: 1062-1070.
12. Hsu CD, Witter FR. Urogenital infection in preeclampsia. Int J Gynaecol Obstet 1995; 49: 271-275.
13. Gunnlaugsson SR, Geirsson RT, Snaedal G, Hallgrimsson JT. Incidence and relation to parity of pregnancy-induced hypertension in Iceland. Acta Obstet Gynecol Scand 1989; 68: 599-601.
14. Saftlas AF, Olson DR, Franks AL, Atrash HK, Pokras R. Epidemiology of preeclampsia and eclampsia in the United States, 1979-1986. Am J Obstet Gynecol 1990; 163: 460-465.
15. Xiao J, Shen F, Xue Q, Chen G, Zeng K. Is ethnicity a risk factor for developing preeclampsia? An analysis of the prevalence of preeclampsia in China. J Hum Hypertens 2014; 28: 694-698.
16. Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ 2005; 330: 565.
17. Berkowitz KM. Insulin resistance and preeclampsia. Clin Perinatol 1998; 25: 873-885.
18. Yogev Y, Xenakis EM, Langer O. The association between preeclampsia and the severity of gestational diabetes: the impact of glycemic control. Am J Obstet Gynecol 2004; 191: 1655-1660.
19. Drobny J. Metabolic syndrome and the risk of preeclampsia. Bratisl Lek Listy 2009; 110: 401-403.
20. Sun Y, Yang H, Sun WJ. Risk factors for pre-eclampsia in pregnant Chinese women with abnormal glucose metabolism. Int J Gynaecol Obstet 2008; 101: 74-76.
21. Barden A, Singh R, Walters BN, Ritchie J, Roberman B. Factors predisposing to pre-eclampsia in women with gestational diabetes. J Hypertens 2004; 22: 2371-2378.
22. Kilpatrick DC. Preeclampsia and diabetes. Am J Obstet Gynecol 1997; 177: 243.
23. Siddiqi T, Rosen B, Mimouni F, Khoury J. Hypertension during pregnancy in insulin-dependent diabetic women. Obstet Gynecol 1991; 77: 514-519.
24. Sibai BM, Caritis S, Hauth J, Lindheimer M, VanDorsten JP, MacPherson C. Risks of preeclampsia and adverse neonatal outcomes among women with pregestational diabetes mellitus. In Am J Obstet Gynecol 2000; 364-369.
25. Sibai BM. Risk factors, pregnancy complications, and prevention of hypertensive disorders in women with pregravid diabetes mellitus. J Matern Fetal Med 2000; 9: 62-65.
26. Reaven GM, Lithell H, Landsberg L. Hypertension and associated metabolic abnormalities-the role of insulin resistance and the sympathoadrenal system. N Engl J Med 1996; 334: 74-81.
27. Rowe JW, Young JB, Minaker KL, Stevens AL, Pallotta J, Landsberg L. Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man. Diabetes 1981; 30: 219-225.
28. Ness RB, Markovic N, Bass D, Harger G, Roberts JM. Family history of hypertension, heart disease, and stroke among women who develop hypertension in pregnancy. Obstet Gynecol 2003; 102: 1366-1371.
29. Sanchez SE, Zhang C, Qiu CF, Williams MA. Family history of hypertension and diabetes in relation to preeclampsia risk in Peruvian women. Gynecol Obstet Invest 2003; 56: 128-132.
30. Qiu C, Williams MA, Leisenring WM, Sorensen TK, Frederick IO. Family history of hypertension and type 2 diabetes in relation to preeclampsia risk. Hypertension 2003; 41: 408-413.
31. Klonoff-Cohen HS, Cross JL, Pieper CF. Job stress and preeclampsia. Epidemiology 1996; 7: 245-249.
32. Sullivan P, Schoentgen S, DeQuattro V, Procci W, Levine D, Meulen JV. Anxiety, anger, and neurogenic tone at rest and in stress in patients with primary hypertension. Hypertension 1981, 6: 119-123.
33. Potter WZ, Manji HK. Catecholamines in depression-an update. Clin Chem 1994; 40: 279-287.
34. Kurki T, Hiilesmaa V, Raitasalo R, Mattila H, Ylikorkala O. Depression and anxiety in early pregnancy and risk for preeclampsia. Obstet Gynecol 2000; 95: 487-490.
35. Qiu C, Williams MA, Calderon-Margalit R, Cripe SM, Sorensen TK. Preeclampsia risk in relation to maternal mood and anxiety disorders diagnosed before or during early pregnancy. Am J Hypertens 2009; 22: 397-402.
36. Landsbergis PA, Hatch MC. Psychosocial work stress and pregnancy-induced hypertension. Epidemiol 1996; 7: 346-351.
37. Lee CJ, Hsieh TT, Chiu TH, Chen KC, Lo LM. Risk factors for pre-eclampsia in an Asian population. Int J Gynaecol Obstet 2000; 70: 327-333.