Comparative analysis of cardio metabolic profile before and after 34 weeks in Ghanaian preeclamptic patients

Background: Over the past decade there has been an increased focus on the link between the history of preeclampsia and cardio metabolic syndrome a danger signaling event. The impact of this event is now becoming alarming in developing countries but data is scanty. Hence the need to collate information in Ghana. Aim: To compare cardio metabolic profile of preeclampsia before and after 34 weeks in Ghana Methodology: The nested case control study was located at the Obstetrics and Gynecology department of the Korle-Bu Teaching Hospital (KBTH). One hundred and sixty-four (164) consented subjects were recruited after ethical clearance was obtained and structured questionnaire administered to them. Four (4) ml blood and 5 mL urine samples were taken for biochemical analysis and urinalysis respectively. Randox automated chemistry analyzer was used to quantify blood chemistry. The data was captured as protected health information (PHI) and analyzed with SPSS version 18. Results: In preeclampsia, increased cardio metabolic scores before term were associated with low birth weight while lactate dehydrogenase (LDH) increased before 34 weeks and rather decreased after 34 weeks. Systolic blood pressure (SBP), white blood cells (WBC) and aspartate transaminase (AST) increased as well in PE clients while platelet (PLT), low density lipoprotein (LDL) and birth weight decreased when these variables were doubly stratified by weeks of gestation and cardio metabolic profile. Conclusion: Among preeclampsia, increased cardio metabolic profile before term were associated with low birth weight. Correspondence to: Ababio GK, University of Ghana SBAHS, Department of Medical Biochemistry, Accra, Ghana, E-mail: graceababio2002@yahoo.com

However, it remains unclear whether pregnancy induced hypertensive women and or preeclampsia have altered levels of cardio metabolic profiles before pregnancy or whether the conditions arise due to disturbances induced by the pregnancy itself. A better understanding of the underlying pathophysiology of preeclampsia (PE) is therefore needed for early intervention. Cardiometabolic profile might provide such platform of data support, since increasing risk is seen in the pathogenesis of PE.
PE is a multifactorial disorder with no specific identifiable etiology and accounting for 5-7% of all pregnancies with significant maternal and perinatal morbidity and mortality [30][31]. Most of the studies into the etiology and the pathogenesis of preeclampsia [30][31][32] had been conducted in the developed world with limited data in the developing countries such as Ghana. It is therefore imperative that such studies be replicated in our indigenous women to provide evidence base information to aid in the prevention and management of preeclampsia and its complications. The current research thereby seeks to investigate the role of cardio metabolic risk on the pathogenesis and outcomes of PE in the Ghanaian population.  Fasting serum glucose ≥110 mg/dl. Cardio metabolic scoring profile: Each risk factor of cardiometabolic profile was divided into the categories shown in Table 1.

Inclusion and exclusion criteria:
Only patients diagnosed with PE were recruited after obtaining their consent as cases. Control subjects included normotensive pregnant and non-pregnant women who gave informed consent. Patients with a history of renal disease, chronic hypertension, diabetes, molar pregnancy, urinary tract infection, thyroid dysfunction and infectious diseases were excluded.
Blood collection and processing: Four milliliter (4 ml) blood was drawn from an antecubital vein by means of a plastic syringe and dispensed into EDTA (for FBC) and gel tubes taking careful precautions. Sysmex hematological auto analyzer was used to quantify FBC whilst RANDOX auto analyzer was used for the determination of lipid profile, LDH and creatinine levels.
Urinalysis: Five mL spot urine was obtained to determine proteinuria and to categorize subjects into normotensives and PE.
For the purposes of this study, PE was defined based on American College of Obstetricians and Gynecologist criteria. Accordingly, PE is defined as diastolic blood pressure of ≥ 90 mmHg and or systolic blood pressure of ≥140 mmHg with proteinuria ≥300 mg/dl occurring after 20 weeks of gestation.

Data management
The integrity of patient records, ethics and data protection were taken into consideration. Data were created on a spreadsheet, corrected for errors, three (3) different backups created and SPSS version 18 used for analysis.

Results
The study was completed by 164 subjects ( Table 2). The ratio of pregnant normotensives to controls to PE was 1:1:1 respectively. Majority of the subjects were close to the study site, Accra (Table 2) with few exceptional referral PE cases from other parts of the country. All subjects attained at least some level of education while artisan formed the major occupation of these subjects. Significant statistical differences were observed in a major number of clinical variables studied except BMI (Table 3). Also, with the exception of a decreased platelet among PE clients; systolic blood pressure (SBP), diastolic blood pressure (DBP), liver enzymes, urine protein, urine pH, white blood cells (WBC), lipids, lactate dehydrogenase (LDH) and cardio metabolic profile significantly increased. However, when some of these variables were doubly stratified by the weeks of gestation and cardio metabolic profile; SBP, WBC and aspartate transaminase (AST) increased in PE clients while platelet (PLT), low density lipoprotein (LDL) and birth weight decreased (Table 4). LDH, on the other hand, increased with lesser weeks of gestation and rather decreased after 34 weeks in PE subjects. The hypothesis that cardio metabolic profile contributes significantly to the pathogenesis and outcomes of PE was also tested ( Table 4 and 5). Table 1 scoring system was used in calculating cardiometabolic profile.

Discussion
In this study, a report on the association of cardio metabolic profile 'before and after' 34 weeks and adverse pregnancy outcomes were presented. We found significantly increased cardio metabolic profile before term was associated with low birth weight. We have also formulated a sensitive but simple method of calculating cardio metabolic profile to aid clinicians in assessment of future risk of developing the syndrome in PE. This study adds unto the existing knowledge elsewhere that the relationship between cardio metabolic scores and adverse pregnancy outcomes were inversely related [33,34].
Barden and others [35] also suggested that predisposition to metabolic syndrome sensitized women to develop preeclampsia. Even though the present study depicted this trend, lack of extensive patient follow-ups and their relocation and or moving back to their various destinations affected further sampling parameters. Notwithstanding, data from Norwegian research indicated a two-fold and four-fold increase of PE with body mass index (BMI >27.08 kg/m 2 ) and blood pressure (SBP >121 mmHg and DBP > 71 mmHg) respectively [36]. A meta-analysis had also confirmed the relationship of hypertension to lower birth weight and head circumference, as well as the importance   of catch-up growth [37]. However, when this same type of analysis were restricted to studies with published correlations between systolic BP and birth weight, the association was not so strong; an indication of other eminent factors [1][2][3][4][5]11] in the environ which could possibly cause such effects [37,38].
There is also evidence outside of pregnancy that increased leukocyte counts within normal range were associated with metabolic disorders in women [39,40]. Other findings suggested that slightly increased leukocyte counts may modestly be associated with the development of pregnancy induced hypertensive disorder. However, leukocyte count alone was relatively a non-specific marker of inflammation due to it being influenced by other factors such as infection and certain medications [41]. Data from Kaiser Permanente MHC also showed that inflammation as measured by increased leukocytes was predictive of hypertension but were unable to present the potential mechanism [42,43]. We are by this study suggesting that preeclampsia (PE), through the cardio metabolic signaling pathway was as a result of the modification of LDL to form ox-LDL which did trigger foam cell formation. This was because of the relatively low LDL levels observed. Current literature also suggested that upon activation of macrophage system (foam cells) by ox-LDL [12][13][14][15][16][17][18][19], primary mediators like cytokines or chemokines elicited the recruitment of secondary mediators e.g. white blood cells (WBC) to thus impair the endothelial system.
Despite the well-intentioned efforts at making laboratory diagnosis of PE and it complications especially HELLP syndrome (Haemolysis, Elevated liver enzymes and low platelets) based on the presence of hemolysis, elevations of liver enzymes (AST, ALT), LDH and proteinuria, substantial inter-laboratory differences remain a major problem. This was partly due to the cutoff point or reference ranges used to establish an abnormal test and the different number of assays used to measure these tests. In this study, the standardized hospital protocol was used to ascertain the various parameters.

Conclusion
In preeclampsia, increased cardio metabolic profiles before term were associated with low birth weight.   Table 4. Cardio metabolic profile, weeks of gestation and some indicators.