|Year : 2018 | Volume
| Issue : 2 | Page : 145-149
Lipids and uric acid in mid-second trimester and prediction of adverse pregnancy outcome
Ahmed M El-Ewa, Seham Abd-El-Halim El-Berry, Khalid M Salama, Naglaa Y.I. El-Maghraby
Gynecology and Obstetric Department, Faculty of Medicine, Benha University, Egypt
|Date of Submission||04-Feb-2018|
|Date of Acceptance||15-Mar-2018|
|Date of Web Publication||17-Aug-2018|
Dr. Naglaa Y.I. El-Maghraby
Gynecology and Obstetric Department, Faculty of Medicine, Benha University, El-Sharkia, 44511
Source of Support: None, Conflict of Interest: None
Background Studies have shown that abnormal metabolism may be a potential contributor to endothelial cell dysfunction and adversely affect the pregnancy outcome.
Aim To measure the concentrations of serum lipids and uric acid (UA) in the healthy nulliparous women in mid-second trimester and to assess the predictive values of these metabolic markers for adverse pregnancy outcome.
Patients and methods The study was conducted on 500 healthy nulliparous women in second trimester who attended the outpatient clinic of Banha University to predict any pregnancy outcomes. Lipids and UA concentrations were measured in mid-second trimester of pregnancy, and the odd ratios and 95% confidence interval were estimated with unconditional logistics regression adjusting for maternal age and BMI.
Results The mean serum UA was statistically significantly higher in preeclampsia and gestation diabetes mellitus (GDM). We found differences in patients with preeclampsia and normotensive patients (4.77±0.99 vs. 3.15±1.07 mg/dl) and patients with GDM and non-GDM (5.94±0.77 vs. 3.29±1.09 mg/dl) but not in preterm birth. A positive correlation of serum UA with adverse pregnancy outcome was found (r=0.57, P=0.00). Serum lipids were statistically significant in prediction of adverse pregnancy outcomes. The odd ratios and 95% confidence interval of triglycerides, low-density lipoproteins, high-density lipoproteins, and total cholesterol were r=0.35, P=0.00; r=0.29, P=0.00; r=0.39, P=0.00; and r=0.63, P=0.00, respectively. Total cholesterol and triglyceride were positively correlated.
Conclusion The combination of serum lipid profile and serum UA in mid-second trimester can be used to predict adverse pregnancy outcomes.
Keywords: adverse pregnancy outcomes, lipids, uric acid
|How to cite this article:|
El-Ewa AM, El-Berry SA, Salama KM, El-Maghraby NY. Lipids and uric acid in mid-second trimester and prediction of adverse pregnancy outcome. Benha Med J 2018;35:145-9
|How to cite this URL:|
El-Ewa AM, El-Berry SA, Salama KM, El-Maghraby NY. Lipids and uric acid in mid-second trimester and prediction of adverse pregnancy outcome. Benha Med J [serial online] 2018 [cited 2018 Oct 17];35:145-9. Available from: http://www.bmfj.eg.net/text.asp?2018/35/2/145/239190
| Introduction|| |
During pregnancy, maternal metabolism must satisfy the demands of the developing fetus in addition to the energy requirement of the mother. The maternal lipid metabolism is specifically altered during pregnancy, as cholesterol and phospholipids are increased moderately, whereas plasma triglyceride (TG) levels rise markedly .
Studies have shown that abnormal metabolism may be a potential contributor to endothelial cell dysfunction. Both low-density lipoprotein cholesterol (LDLc) and TG-rich lipoproteins trigger endothelial dysfunctional atherothrombosis, whereas high-density lipoprotein cholesterol (HDLc) exerts a protective effect on endothelium-dependent vasodilatation .
Uric acid (UA) decreases by 25–35% in early pregnancy but increases toward normal concentrations near term in normal pregnancy . UA can induce endothelial dysfunction and insulin resistance. Endothelial dysfunction and atherothrombosis are characteristic vascular changes in patients with preeclampsia (PE) and gestation diabetes mellitus (GDM); therefore, it was found that pregnant women with elevated LDL concentrations experienced a 2.9-fold increased risk of PE, and those with high cholesterol or TGs at 15 weeks of gestation had a 2.8-fold risk for preterm birth (PTB) .
Additionally, it was reported that first trimester hyperuricemia increased the risk of developing GDM and mild PE, independent of BMI, and was associated with lower birth weight in normotensive women . The association of abnormal lipid metabolism in essential hypertension is well documented. In early pregnancy, there is increased body fat accumulation associated with increased lipogenesis, whereas in late pregnancy, there is accelerated breakdown of fat deposits, which play an important role in fetal development. Early pregnancy dyslipidemia is associated with an increased risk of PE. 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 .
In most developed countries, pregnancies are planned, complications are few, and outcomes are generally favorable for both mother and infant. Adverse outcomes are far more frequent in the developing world. Maternal death has become an extremely rare event in the developed world, with many countries reporting maternal mortality ratios of 5–10 per 100 000 live births. In the least developed countries, the ratios are 100 times higher .
Disparities in infant deaths are not quite as wide but remain substantial, ranging from 4–5 to more than 100 per 1000 live births. Wide disparities probably also exist in the rate of late fetal deaths (stillbirths), although fetal deaths in developing countries are grossly underreported. Even if both the mother and infant survive, pregnancy complications or problems at delivery or during the neonatal period can lead to increased maternal or infant morbidity .
GDM and PE are two common complications in pregnancy, affecting more than 10% pregnancies worldwide. However, the true underlying causes of these two conditions remain to be fully elucidated. Although both conditions were diagnosed first during pregnancy, it is uncertain whether they originate before or during pregnancy .
| Aim|| |
The predictive values of these metabolic markers for adverse pregnancy outcomes were analyzed.
| Patients and methods|| |
This study is a prospective observational study. It includes 500 nulliparous women attending Antenatal Outpatient Department of Benha University Hospital, Benha Teaching Hospital, and Minia, El-Kamh Central Hospital.
Approval of Research and Ethics Committee was obtained, and written informed consent was taken from each patient, after explanation of every step in the study.
The inclusion criteria were pregnant women less than 20 weeks of gestation and nulliparous apparently healthy women.
The exclusion criteria were as follows: multiparous pregnancy, women having a family history of dyslipidemia, and women having chronic diseases that may affect the lipid profile such as hypertension, diabetes, and SLE.
All women underwent routine obstetric care and routine investigation. Pregnancy outcomes were followed up till the end of pregnancy for development of PE, GDM, and PTB according to Cunningham et al.  and ADA criteria for the diagnosis of GDM .
All cases were seen before 20 weeks of gestation. Each case had her own booking and follow-up sheet. All cases were subjected to the following:
- History: present, past, family, and obstetric histories.
- General Examination and Abdominal Examination Auscultation: FHS by the sonic aid 10 weeks of pregnancy and from 20 weeks onwards by Pinard stethoscope rate 120–160/beats/min.
- Laboratory studies: all routine ANC laboratory studies were done, including urine analysis (microscopic, culture, proteins, and sugar) and blood analysis (blood grouping, Rh, complete blood count, rubella antibodies, hepatitis B virus surface antigen, and UA). The lipid profiles were tested following a 12-h overnight fast at 20 weeks of gestation. Serum TG, total cholesterol, LDLc, and HDLc concentrations were determined by standard enzymatic methods (Cobas Integra 800; Roche, Berlin, Germany). UA was measured using a colorimetric assay (Sbin React 800; Spain).
- Acid was measured using a colorimetric assay (Sbin React 800; BECKMAN COULTER DU 800 SPECTROPHOTOMETER, Beckman-Coulter, Harbor Blvd., Fullerton, CA, USA).
Normal range of UA is as follows: adult women normally have levels between 2 and 6.5 mg/dl and in women older than 40, between 2 and 8 mg/dl. In human blood plasma, the reference range of UA is typically 3.4–7.2 mg/dl for men and 2.4–6.1 mg/dl for women .
UA can decrease by 25–35% in early pregnancy but increase toward normal concentration near term in normal pregnancy .
Overall cholesterol levels should be normally between 135 and 200 mg/dl, LDLc should be less than 130 mg/dl, and HDLc should be above 30 mg/dl .
| Results|| |
[Table 1] presents maternal characteristics of our study population. Among 500 mothers in the present study, all cases were nulliparous, with BMI more than 26.31 kg/m2.
As seen in [Table 2], 45 (9%) of patients developed PE, 25 (5%) developed GDM, and 15 (3%) had PTB, where four of them had PE, two had GDM, and one had both of them. The median age of the patients with PE was 30 years (range: 19–41) old, and almost 70% of women had MABP of more than 120 mmHg. The median BMI of patients with PE was 31.12 kg/m2. More than 80% of cases of elevated serum UA were seen in patients with PE with BMI more than 26 kg/m2.
[Table 3] shows the data for predictors of PE in patients (n=45; 9%). There were highly significant differences between patients with PE and the non-PE. BMI, TG, HDL, and UA were highly significantly in PE.
[Table 4] shows the predictors of GDM (n=25; 5%). Regarding all parameters, there were highly significant differences between GDM and non-GDM.
[Table 5] shows the predictors of PTB, and there were NS differences between PTB group and non-PTB group regarding level of HDL (P=0.16) ([Table 6] and [Table 7]).
|Table 6 Odds ratios and 95% confidence interval for risk of adverse pregnancy outcomes|
Click here to view
|Table 7 Receiver operating characteristic of metabolic markers in mid-second trimester in the prediction of adverse pregnancy outcome|
Click here to view
| Discussion|| |
In the present study, we found that UA and lipids were increased and were highly significant with PE and GDM, whereas LDHc was decreased in PE, GDM, and PTB in mid-second trimester.
These results are in agreement with previous studies which showed that increased TG and UA in adverse pregnancy outcomes such as PE and GDM and decreased LDHc in PTB ,,,,,,.
Women with PE present significantly higher values for total cholesterol and also UA was positively correlated with PE.
Elevated UA is another component of the PE syndrome. It is one of the most consistent and earliest detectable changes in PE and has been cited as a better predictor of fetal risk than blood pressure .
Dyslipidemia in pregnancy is associated with GDH, PE, PTB, and other adverse outcomes, during pregnancy in first, second, and third trimesters. Maternal high TG concentrations in late pregnancy are associated with increased risk of GDH, PE, ICP, LGA macrosomia, and PTB and a decreased risk of SGA .
However, we were still convinced to measure lipids and UA levels in mid-second trimester for prediction of adverse pregnancy outcomes, as the identification of hypertriglyceridemia as risk factors for PE and GDM may help to identify pregnant was lifestyle modifications and dietary modifications have been reported as efficient interventions that may prevent the dyslipidemia. If such strategy is also found to be efficacious in preventing PE and GDM in dyslipidemia pregnant women, the finding of our study may facilitate efforts to prevent these most common pregnancy complications, when the predictive sensitivity for the combination of these metabolic markers were 80–92%.
In contrast to our results, several studies have reported that UA is nonsignificantly associated with PE and GDM, and lipid is also nonsignificantly associated with adverse pregnancy outcomes ,,,.
The conflicting consequences implied that maternal lipid concentrations were influenced by complicated factors (e.g. condition of glycemic control, trimester of pregnancy, and race/ethnicity).
| Conclusion|| |
Altered lipid profile has a potential role in the genesis of endothelial dysfunction and expression of PE. Early detection of these parameters may help patient by preventing complications in PE, and GDM is going to aid in better management of PE. Hyperuricemia is as effective as proteinuria in identifying gestational hypertensive pregnancies at increased risk.
Financial support and sponsorship
Conflicts of interest
| References|| |
Mankuta D, Elami-Suzin M, Elhayani A, Vinker S. Lipid profile in consecutive pregnancies. Lipids Health Dis 2010; 9:58.
Felmeden DC, Spencer CG, Blann AD, Beevers DG, Lip GY. Low-density lipoprotein subfractions and cardiovascular risk in hypertension: relationship to endothelial dysfunction and effects of treatment. Hypertension 2003; 41:528–533.
Igarashi M, Miyake H, Suzuki S. Effect of changes in renal circulation on serum uric acid levels in women with twin pregnancy. Clin Exp Nephrol 2010; 14:436–439.
Ho WJ, Tsai WP, Yu KH, Tsay PK, Wang CL, Hsu TS, Kuo CT. Association between endothelial dysfunction and hyperuicaemia. Rheumatology 2010; 49:1929–1934.
Wolak T, Sergienko R, Wiznitzer A, Paran E, Sheiner E. High uric acid level during the first 20 weeks of pregnancy is associated with higher risk for gestational diabetes mellitus and mild preeclampsia. Hypertens Pregnancy 2012; 31:307–315.
Enquobahrie DA, Williams MA, Butler CL, Frederic IO, Miller RS, Luthy DA. Maternal plasma lipid concentrations In early pregnancy and risk of preelampsia. AM J Hypertens 2004; 17:574–581.
AbouZhar C, Wardlaw T. Maternal mortality at the end of decade: What are signs of progress? Bull World Health Organ 2001; 79:561–573.
Tinker V, Giri P, Mahajian A. Maternal and neonatal outcome in preeclamsia. Int J Pharm Sci Res 2000; 1:145–160.
Cekmen MB, Erhagci AB, Balat A, Duman C, Maral H, Ergen K et al.
Plasma lipid and lipoprotein concentrations in pregnancy induced hypertention. Clin Biochem 2003; 36:575–578.
Cunningham F, Mac-Donald P, Gan N. Hypertensive disorders of pregnancy. In: Laveno K, editor. Williams obstetric. 23rd ed. London: Prentice-Hall International Inc; 2010. p. 706.
Kartez A, Ferraro M, Sluss P. Case records of the Massachusetts General Hospital: laboratory values. N Eng J Med 2004; 351:1549–1563.
Parekh A, Jung D. Serum inorganic phosphorus determination using p-phenyl-enediamine as reducing agent. Clin Chim Acta 2001; 27:373–388.
Martin AC, Brown MA, Kang DH. Could uric acid have a pathogenic role in preeclampsia. Nat Rev Nephrol 2010; 6:744–748.
Zhou J, Zhao X, Wang Z, Hu Y. Combination of lipids and uric acid in mid-second trimester can be used to predict adverse pregnancy outcomes. J Matern Fetal Neonatal Med 2012; 25:2633–2638.
Mythili D, Rani AJ. Uric acid in type 2 diabetes mellitus. Hypertension 2013; 12:14.
Jin WY, Lin SL, Hou RL, Chen XY, Han T, Jin Y et al.
Association between maternal lipid profile and pregnancy complications and perinatanl outcomes. BMC Pregnancy Childbirth 2016; 16:60.
Gohil JT, Patel PK, Gupta P. Estimation of lipid profile in subjects of preeclampsia. J Obstet Gynaecol India 2011; 61:399–403.
Dey M, Arora D, Kumar R. Serum cholesterol and ceruloplasmin levels in second trimester can predict development of preeclampsia. N Am J Med Sci 2013; 5:41–46.
Enaruna NO, Joseph OI, Paul IA. Serum lipid profile and acid in preeclampsia in University of Benin Teaching Hospital. Niger Med J 2014; 55:423–427.
] [Full text]
Vrjkotte TG, krukziener N, Hutten BA, Vollebreget KC, van Ejsden M, Twickler MB. Maternal lipid profile during early pregnancy and pregnancy complications and outcomes: the ABCD study. J Clin Endocrinol Metab 2012; 11:3917–3925.
Ryckman KK, Spracklen CN, Simth CJ, Saftlas AF. Maternal lipid levels during pregnancy and gestational diabetes: a systematic review and meta-analysis. BJOG 2015; 122:643.
Savona-Ventura C, Vassallo J, Craus J, Anastasious E, Jotic A, Lalic NM et al.
Biological and biochemical characteristic of a Mediterranean with gestational diabetes mellitus population. J Perinat Med 2015; 44:377–382.
El‑Gharib MN, Mahfouz AE, Morad MA, Farahat MA. Prediction of gestational diabetes by measuring first trimester maternal serum uric acid concentration. J Basic Clin Reprod Sci 2013; 2:27–31.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]