Hypertension in Pregnancy

ISSN: 1064-1955 (Print) 1525-6065 (Online) Journal homepage: http://www.tandfonline.com/loi/ihip20

Value of first-trimester serum lipid profile in early prediction of preeclampsia and its severity: A prospective cohort study Nabih I. El Khouly, Zakaria F. Sanad, Said A. Saleh, Ayman A. Shabana, Alaa F. Elhalaby & Eman E. Badr To cite this article: Nabih I. El Khouly, Zakaria F. Sanad, Said A. Saleh, Ayman A. Shabana, Alaa F. Elhalaby & Eman E. Badr (2016): Value of first-trimester serum lipid profile in early prediction of preeclampsia and its severity: A prospective cohort study, Hypertension in Pregnancy, DOI: 10.3109/10641955.2015.1115060 To link to this article: http://dx.doi.org/10.3109/10641955.2015.1115060

Published online: 01 Feb 2016.

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Date: 03 February 2016, At: 15:20

HYPERTENSION IN PREGNANCY http://dx.doi.org/10.3109/10641955.2015.1115060

Value of first-trimester serum lipid profile in early prediction of preeclampsia and its severity: A prospective cohort study Nabih I. El Khouly, Zakaria F. Sanad, Said A. Saleh, Ayman A. Shabana, Alaa F. Elhalaby, and Eman E. Badr

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Department of Obstetrics and Gynecology, Faculty of Medicine, Menoufia University, Shibin Elkom, Egypt ABSTRACT

KEYWORDS

Study objective: The purpose of this study was to evaluate the association of first-trimester serum lipid profile with preeclampsia (PE) and if so, its association with the severity of the disease. Study: Prospective cohort study. Patient and methods: A total of 251 pregnant women participated in this study in their first trimester. Maternal blood samples were collected between 4 and 12 weeks of gestation. Fasting serum triglycerides (TGs), total cholesterol (TC), HDL-cholesterol, and low-density lipoprotein cholesterol (LDL-C) were drawn and measured by ELISA. From the cohort, 26 women developed PE (16 mild and 10 severe) and 174 remained normotensive and used as control subjects. Results: There was a significant rise in fasting serum TGs, TC, and LDL-C and a significant decrease in HDL-C in women who developed PE than in those who remained normotensive and more significantly evident in severe preeclamptic cases compared to mild cases of PE (p < 0.05). Conclusion: Early pregnancy dyslipidemia, particularly hypertriglyceridemia and hypercholesterolemia, may help in predicting women who later develop PE and may help in prediction of its severity.

Dyslipidemia; lipid profile; preeclampsia

Introduction Preeclampsia (PE), a non-convulsive form of pregnancy-induced hypertension, accounts for a significant proportion of maternal and fetal morbidity and mortality (1). Despite an intensive research effect to elucidate the origin of PE, there is a currently no wellvalidated prophylactic treatment, nor is there any effective method of identifying women with an increased risk of PE (2); however, recent studies have reported that the magnitude of the imbalance between anti-angiogenic (soluble fms-like tyrosine kinase1 (sFlt-1)) and pro-angiogenic (placental growth factor (PlGF)) factors correlates well with disease activity, with a cutoff value of the sFlt-1/PlGF ratio greater than 655 increasing the risk for imminent delivery with a controversial prognostic potential for fetal complications (3–5). Abnormal lipid profiles have a strong positive correlation with endothelial dysfunction. Specific changes are usually associated with normal pregnancy. Normal serum total triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) levels increase toward the term of normal pregnancy (6–8). CONTACT Nabih I. El Khouly, [email protected] Department of Obstetrics and Gynecology, Faculty of Medicine, Menoufia University, Shibin Elkom, Menoufia 32714 Egypt. © 2016 Taylor & Francis

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Prospective studies have demonstrated that the predominance of small, dense LDL precedes the clinical onset of coronary heart disease (9). Small, dense LDL fraction had a greater capacity to stimulate the thromboxane synthesis by endothelial cells and an increase in intracellular calcium in vascular smooth muscles, which might be relevant to vasospasm in PE (10,11). PE is associated with the development of maternal hyperlipidemia, especially hypertriglyceridemia. A dysfunction of the maternal vascular endothelium, which may be induced by hyperlipidemia during pregnancy, occurs in PE (12,13). Women with a history of PE have significant differences in lipid parameters and an increased susceptibility to lipoprotein oxidation when compared with women who had normal pregnancy (14,15). Therefore, simple measurement of serum lipid profile may be of good predictive value in PE. With this background in mind, the present study was conducted to assess lipid profile in cases of PE and normal healthy pregnant women.

Methods This study is a prospective observational cohort study that was conducted at Menoufia University Hospital on a total of 251 pregnant women who attended the obstetric outpatient clinic for routine antenatal care examination in their first trimester, from June 2012 to April 2013; only 200 remained for analysis. Informed consent was taken from all participants. Primigravidas with singleton pregnancies and normal blood pressure were included in this study. All subjects included were in their first trimester, calculated by last menstrual period, and confirmed by ultrasonography (Emperor 2000, China). Subjects suffering from diabetes mellitus with or without treatment, morbid obesity (BMI > 40 kg/m2), other systemic, autoimmune diseases, endocrine disorder, pre-existing hypertension, ischemic heart diseases, chronic renal disease, or treatment with drugs that may influence lipid profile were excluded. Women who had multifetal pregnancies or who had experienced spontaneous or induced abortions were excluded also. PE was diagnosed when hypertension (systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg) and proteinuria (≥300 mg/24 h) appeared after 20 weeks of gestational age in a previously normotensive woman. According to criteria of the American College of Obstetricians and Gynecologists (ACOG) (16) PE was considered severe when one or more of the following was present: systolic blood pressure ≥ 160 mm Hg or diastolic blood pressure ≥ 110 mm Hg on two occasions at least 6 h apart; proteinuria of 5 g or higher in a 24-h urine specimen; impaired liver function (17). Blood samples were drawn from all participants in their first trimester following a fast of 12 h and analyzed for serum TGs, TC, HDL-cholesterol (HDL-C), and LDLcholesterol (LDL-C) concentration. Serum TGs and TC concentration were measured with enzymatic colorimetric method using (ERBACHEM 7 photometer, Germany, Mannheim, Germany), and Spinreact kits, Sant Esteve de Bas, Girona, Spain). HDL-C was separated from LDL-C and very LDL-C by a chemical precipitation technique, and the used precipitating reagent was heparin-manganese chloride; this method was done at room temperature and completed within 10–15 min followed by centrifugation for 30

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min, after which HDL-C was determined in the clear supernatant using spinreact kits and CHEM 7 equipment. LDL-C was obtained using Friedwald’s formula (18). LDL-C = Total cholesterol – (HDL-C–VLDL-C). All concentrations are given in mg/dl. Body mass index was calculated as weight in kilograms divided by the square of height in meters. The data collected were tabulated and analyzed by SPSS (statistical package for the social science software) statistical package version 20 (Chicago Inc., Chicago, Illinois, USA), the following tests were used: quantitative data were expressed as mean and standard deviation (X ± SD) and analyzed by applying Student t test. p-Value at 0.05 was used to determine the significance regarded as non-significant; p > 0.05, significant; p ≤ 0.05 or highly significant; p ≤ 0.001 (19).

Results During the study period from June 2012 to April 2013, baseline characteristics of the participants are shown in Table 1. Women who subsequently developed PE had significantly higher body mass index (p < 0.001) with no difference in maternal age (p = 0.83) and gestational age at enrollment (p = 0.15) from women who remained normotensive. Table 2 lists serum lipid and lipoprotein concentration in both groups—the preeclamptic patients had significantly higher serum levels of TGs (p < 0.0001), TC (p < 0.0001), and LDL-C (p = 0.01) and significantly lower levels of HDL-C (p = 0.01) compared with healthy control. Also, TC (p = 0.009) and TG (p = 0.016) levels were significantly higher in severe preeclamptic cases compared to mild cases of PE (p < 0.05); on the other hand, there was no significant difference between both groups for either LDL-C (p = 0.09) or HDL-C level (p = 0.12) (Table 3) Diagnostic validity of serum lipids in prediction of PE is listed in Table 4, and negative predictive value of serum lipids was high compared to positive predictive value. Cutoff points for fasting serum lipid in the first trimester for prediction of PE determined by receiver operating characteristic curves (ROC curves) are 231 Table 1. Comparison between preeclamptic cases and normotensive controls regarding maternal age, gestational age, and BMI at enrolment. Preeclamptic cases (n = 26) Normotensive controls (n = 174) t-test p-value Maternal age (years) Mean ± SD Range Gestational age at enrolment (weeks) Mean ± SD Range BMI (kg/m2) Mean ± SD Range NS: Non-significant. HS: Highly significant. BMI: Body mass index.

23.50 ± 3.71 18.00–31.00

23.66 ± 3.91 16.00–33.00

0.20

0.83 NS

8.19 ± 2.43 5.00–13.00

8.94 ± 2.55 5.00–13.00

1.41

0.15 NS

8.02

42.50 mg/dl, PE most probably will not occur, so measurement of fasting serum lipid in first trimester has a good exclusive role in our study as shown in Table 4.

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The main limitations of our study are single measurement of lipid profile and the small number of PE patients; however as a pilot study this shows promising results for future larger scale studies to confirm its role in prediction of PE and its severity.

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Conclusion The findings reported in our study suggest that the women who develop PE had disturbed lipid profile. Thus, estimation of lipid profile may have a predictive role in both normal weight and obese patients. Estimation of lipid profile particularly TGs and TC may help in prediction of severity of PE. And lipid profile is a good negative predictive test in excluding the possibility of occurrence of PE when lipid profile is normal according to the suggested cutoff points. Information from this study may contribute to the development and evaluation of behavioral-preconception dietary modification and medical interventions aimed at reducing the future risk of PE especially in cases with past history of PE, or cases with multiple risk factors. Hence, early detection of these parameters is going to aid in better management of PE cases which is important to improve the maternal and fetal outcome in PE.

Conflict of interest None.

Sources of support None.

Funding No financial support or funding was received.

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Value of first-trimester serum lipid profile in early prediction of preeclampsia and its severity: A prospective cohort study.

The purpose of this study was to evaluate the association of first-trimester serum lipid profile with preeclampsia (PE) and if so, its association wit...
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