• Meta-analysis;
  • predictive marker;
  • pre-eclampsia;
  • systematic review;
  • triglycerides


  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References


Elevated triglycerides are a feature of the metabolic syndrome, maternal obesity, maternal vasculitis (i.e. systemic lupus erythematosus) and diabetes mellitus. These conditions are all known risk factors for pre-eclampsia. Hypertriglyceridaemia therefore may be associated with pre-eclampsia and indeed this may precede the presence of overt disease.


In this study we determine the association between hypertriglyceridaemia and pre-eclampsia in pregnant women.

Search strategy

We searched MEDLINE, EMBASE, Web of Science, Excerpta Medica Database, ISI Web of Knowledge, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library from inception until June 2012 and reference lists of relevant studies.

Selection criteria

Two reviewers independently selected studies on pregnant women where triglycerides were measured and women were followed up until the development of pre-eclampsia or selected on the basis of presence of pre-eclampsia and compared with controls.

Data collection and analysis

We collected and meta-analysed the weighted mean differences (WMDs) of triglyceride levels from individual studies using a random effects model.

Main results

We found strong evidence from meta-analysis of 24 case–control studies (2720 women) that pre-eclampsia is associated with higher levels of serum triglycerides (WMD 0.78 mmol/l, 95% confidence interval 0.6–0.96, P < 0.00001). This finding is also confirmed in five cohort studies, that recruited 3147 women in the second trimester before the onset of pre-eclampsia, which proves that hypertriglyceridaemia precedes the onset of pre-eclampsia (WMD 0.24 mmol/l, 95% confidence interval 0.13–0.34, P < 0.0001).

Author's conclusions

Hypertriglyceridaemia is associated with and precedes the onset of pre-eclampsia. Further research should focus on defining the prognostic accuracy of this test to identify women at risk and the beneficial effect of triglyceride-lowering therapies in pregnancy.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

Pre-eclampsia is a multi-organ disorder of pregnancy that manifests after 20 weeks of gestation with new onset hypertension and proteinuria. Pre-eclampsia is defined as blood pressure ≥140 mmHg systolic and ≥90 mmHg diastolic diagnosed for the first time after 20 weeks of gestation together with >300 mg proteinuria/24 hours as defined in the proceedings of the 16th Scientific Study Group of the Royal College of Obstetricians and Gynaecologists.[1] This disease can progress to cause maternal liver dysfunction,[1] renal impairment[2] and ultimately seizures and death.[3] The foetus may suffer intrauterine growth restriction and, when born preterm, is more likely to struggle with the consequences of premature delivery.[4] Women with pre-eclampsia are also more likely to suffer stillbirth or neonatal death.[5] Of equal importance is the consistent finding that these women have an increased lifetime risk of cardiovascular disease compared with the rest of the population.[6, 7] Dyslipidaemia (especially hypertriglyceridaemia) has been reported as being part of the pre-eclampsia disease process.[8] Hypertriglyceridaemia is well documented as an endothelial disruptor in atherosclerosis and is a potential candidate for the endothelial dysfunction seen in this disease. The aim of this study was therefore to perform a systematic review of the literature and meta-analysis to test the hypothesis that elevated triglycerides correlate with increased likelihood of pre-eclampsia.

One of the leading hypotheses in the aetiology of pre-eclampsia is that circulating factors, released from the placenta, alter endothelial function in the maternal circulation.[9] These factors may subsequently alter vasomotor function,[10] angiogenesis,[11] endothelial permeability and downstream activation of other cascades such as thrombosis.[12] A key variable that may be equally important in the pathogenesis of the disease is the overall sensitivity of the maternal endothelium to these circulating factors. This sensitivity may be modulated by maternal disease, including diabetes,[13] chronic hypertension,[14] obesity and, importantly, altered lipid profile.[15] In pregnancy, as a result of both insulin resistance and increased oestrogen, metabolic changes in both the liver and adipose tissue alter circulating triglycerides, fatty acid, cholesterol and phospholipids.[16] As pregnancy continues, this causes hyperlipidaemia consisting principally of increased triglycerides. The mother and foetus can subsequently use these, and so the increase in triglyceride concentrations represents an accessible energy reservoir. Several reports have suggested that women with pre-eclampsia display further changes in lipid metabolism with increases in circulating levels of triglycerides and non-esterified fatty acids.[17] These changes have been reported to be present at early gestation in women who subsequently develop pre-eclampsia, with the dyslipidaemia notably preceding clinical diagnosis far earlier than the presence of known circulating factors associated with pre-eclampsia such as soluble Flt-1 (sFlt-1) or soluble endoglin (sEng).[18, 19] Moreover, serum from women with pre-eclampsia induces greater lipid accumulation in endothelial cells than serum from normal women.[20]


  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

Data sources and search strategy

We conducted a thorough search to identify eligible studies that measured and reported the triglyceride levels in pregnant women and women were followed up until the development of pre-eclampsia or selected on the basis of presence of pre-eclampsia and compared with controls. The hypothesis is to explore the association of hypertriglyceridaemia with pre-eclampsia. The databases searched included MEDLINE, EMBASE, Excerpta Medica Database, ISI Web of Knowledge, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and The Cochrane Library from inception until June 2012. A combination of keywords for pre-eclampsia (‘Pre-eclampsia’, ‘pregnancy-induced hypertension’, ‘eclampsia’, ‘pregnancy’ and ‘hypertension’), for triglycerides (‘triglycerides’, ‘lipids’, ‘hyperlipid*’, ‘dyslipidemia’, ‘cholesterol’) along with their associated Medical Subject and Emtree Headings were used to search MEDLINE, EMBASE and CINAHL. These two populations of keywords were combined using the ‘AND’ function of the database. The Web of Science and The Cochrane Library were searched using the keywords ‘pre-eclampsia’ and ‘triglycerides’. There were no limits or philtres placed on the searches, to ensure maximal sensitivity and no language restrictions were applied. All the reference sections of all articles were reviewed to also identify relevant studies.

Selection of articles

Articles were selected if they included a population of pregnant women, tested for triglyceride levels and followed up until the diagnosis of pre-eclampsia. These studies were expected to be of cohort design. We also selected studies that they measured the triglyceride levels on women with known pre-eclampsia and compared those with controls. Of the 1017 identified articles, 965 did not match our selection criteria based on review of their titles and abstracts conducted by two authors (MV and IDG). These two authors then independently reviewed the full text of the remaining 52 articles to determine inclusion or exclusion (Figure 1). We excluded 23 studies after evaluation of the full manuscripts. The most common reason for exclusion was our inability to extract raw data from the published reports (18 studies). Finally, 29 studies were deemed eligible for inclusion of which, 24 case–control studies[21-44] and five comparative cohort studies.[45-49] When duplicate data were published, only the most up-to-date, larger series was included. Any disagreements about study eligibility were resolved by consensus, with arbitration by a third reviewer (AC) if necessary.


Figure 1. Flowchart of the study selection process.

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Data extraction

Data were extracted from the eligible studies by two authors (MV and IDG) using a piloted data extraction form. We collected information on definition and diagnosis of pre-eclampsia, gestational age at testing and diagnosis, timing and method of triglyceride measurements and fasting or non-fasting status of the participants. The majority of the papers reported triglyceride measurements in millimolar and for few papers that reported data in milligram per decilitre measurements were converted to millimolar. From eligible studies we extracted mean and standard deviations (SDs) of triglyceride measurements from women with pre-eclampsia compared with controls. When medians and 95% confidence intervals (95% CI) were reported instead we assessed the skewness and if acceptable we presumed a normal distribution of the triglyceride levels across women included in the study and we computed the means and SDs. Two reviewers (MV and IDG) completed the quality assessment using the Newcastle–Ottawa Quality Assessment Scales for observational studies. We awarded studies a maximum of nine stars for case–control studies and eight for cohort studies (Figure 2). Any differences were resolved by consensus.


Figure 2. Newcastle–Ottawa quality assessment of the studies.

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Data synthesis

Triglyceride levels between women with pre-eclampsia compared with healthy women were compared by weighed mean differences (WMDs). The WMDs from individual studies were meta-analysed using a random effects model. Studies were weighted by the inverse of the variance and random effects models were used as standard, as they give conservative estimates of effect.[50] We planned a priori subgroup analyses for important confounders that include gestational age, fasting status and body mass index (BMI), at the time of triglyceride measurement, and study design for potential clinical heterogeneity across the studies. Statistical analyses were performed using RevMan 5.0 (Cochrane Collaboration, Oxford, UK) and Stata 9.0 (Stata Corp, College Station, TX, USA).


  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

The studies involved 5857 participants: 1467 women with pre-eclampsia and 4400 healthy women. The main study characteristics of the studies included in this review are summarised in Tables 1 and 2. The included studies were mainly case–control studies carried out in the third trimester (Table 1). The cohort studies recruited women prospectively in the second trimester and followed up women during their pregnancy until the diagnosis of pre-eclampsia (Table 2). In 17 studies the measurements of the triglyceride concentrations were carried out on fasting blood samples. The definition of cases and controls was considered adequate in most case–control studies (2/24 and 23/24, respectively). Often the recruitment of the cases and controls was poorly defined and it was not representative of the population (15/29 for both quality criteria). Controls were commonly matched for gestational and/or maternal age (6/24) and the triglyceride concentrations were measured in similar manner with a similar non-response rate. The five cohort studies were considered of high quality except for three studies that did not adequately describe the selection of the cases and the controls.

Table 1. Characteristics of the case–control studies
Study, yearCasesControlsTriglyceride (TG) test
Barden, 1999 (n = 146)

Women with pre-eclampsia (n = 62) after 20 weeks of gestation

Excluded: None

Age and gestation-matched controls (n = 84)TGs were determined antenatally without fasting. Determined enzymatically using Abbott reagents on a COVASMIRA analyser (Roche Diagnostics, Basel, Switzerland)
Belo, 2004 (n = 118)

Women with pre-eclampsia (n = 51) at a mean gestational age of 34 weeks (SD 4.8)

Excluded: Women with significant obstetric disease or pregnancy-unrelated complications

Primigravidas at different gestational ages with samples taken at third trimester (n = 67)Non-fasted serum samples were obtained at the third trimester of gestation. Serum lipid analysis was performed in an auto-analyser (Cobas Mira S, Roche; Basel, Switzerland) using commercially available kits. TG concentrations were determined by enzymatic colorimetric tests (GPO–PAP methods, Roche)
De, 2006 (n = 100)

Women with pre-eclampsia (n = 50)

Excluded: Women with cardiac, renal, hepatic dysfunction or dyslipidaemia

Women with normal uncomplicated pregnancies (n = 50)Blood samples were drawn from all the women following a fast of 12 hours and analysed for TG by enzymatic methods with the help of Glaxo kits on ERBA Chem-5 semi auto analyser
Francoual, 1999 (n = 50)

Women with mild (n = 23) and severe (n = 12) pre-eclampsia at a mean gestational of 29 ± 3 and 30 ± 5 weeks, respectively

Excluded: None

Normotensive women (n = 15) throughout gestation without proteinuria or hyperuricaemia with no history of chronic hypertension, diabetes, renal or cardiovascular diseaseBlood samples were obtained after 12 hours of fasting. Serum total TG were analysed on a Hitachi 717 analyser (Boehringer Mannheim, Mannheim, Germany)
Gratacos, 1996 (n = 155)

Women with mild (n = 20) or severe (n = 20) pre-eclampsia and for whom samples were available for all three trimesters

Excluded: Women with diabetes, chronic hypertension endocrine or metabolic disorder

Normotensive healthy pregnant women(n = 115) delivering at term without any of the exclusion criteria and with similar blood samples. Matched for age and BMIBlood samples were obtained after overnight fast. Serum TG were measured by enzymatic methods (Trinder, Bayer Diagnostics, Tarrytown, NY, USA) adapted to a Cobas Mira automated analyser (Hoffmann Larroche, Basel, Switzerland)
Gratacos, 2003 (n = 70)

Women with severe pre-eclampsia and singleton pregnancies (n = 35)

Excluded: Women with pre-existent hypertension, diabetes or other chronic disease, previous pregnancy within 6 months and use of oral contraception

Women with normal pregnancies matched for age, BMI, smokingand parity (n = 35)Fasting serum samples were analysed and TG levels were measured by enzymatic methods (Trinder, Bayer Diagnostics) adapted to a Cobas Mira automated analyser (Hoffmann)
Harsem, 2007 (n = 81)Women with pre-eclampsia and singleton pregnancies delivered by caesarean section (n = 40)Women with uncomplicated pregnancies undergoing elective caesarean section (n = 41) between 37 and 42 weeksBlood was sampled before caesarean section from 88 of the 102 women in gel vials and left at room temperature for 30–60 minutes until centrifugation at 2000 g for 10 minutes at room temperature, and serum was stored at −76°C until analysis. Serum concentration of TGs was determined by routine enzymatic methods on a Cobas Integra instrument (Roche)
Hubel, 1998 (n = 40)

Women with pre-eclampsia (n = 20) at the time of admittance to hospital at a median gestational age of 34.5 weeks

Excluded: Women with cigarette or illicit drug use, chronic hypertension, renal disease, or a previous history of metabolic disorders

Women with normal pregnancies matched for gestational age (n = 20)Blood samples were obtained before labour and were non-fasting. Serum was obtained using dry sterile tubes in which the blood was allowed to coagulate for 60 minutes at room temperature before centrifugation. Serum and plasma samples were immediately stored at −70°C (without thawing) until enzymatic analysis of TG concentrations
Khaliq, 2000 (n = 60)

Women with pre-eclampsia (n = 40) and singleton pregnancies and not on any medications

Excluded: Women with cardiac, hepatic, renal or metabolic or history of hypertension

Women with normal pregnancies (n = 20)Blood samples were collected early morning on empty stomach. The concentration of serum TG was measured by GPO-PAP method
Kharb, 1998 (n = 45)

Women with pre-eclampsia (n = 20)

Excluded: Women with diabetes, renal disease, primary hypertension or other systemic disease

Normotensive pregnant women (n = 25)Blood samples were taken before anti-hypertensive treatment
Lei, 2011 (n = 233)Women with singleton pregnancies and pre-eclampsia (n = 33) at a median gestational age of 36 and range 33–39 weeksNormotensive women at the time of admission to hospital (n = 200) at a median gestational age of 38 and range 38–40 weeksBlood samples were collected after women had fasted for 8–10 hours for the analysis of TG concentrations
Llurba, 2004 (n = 83)

Women with singleton pregnancies and pre-eclampsia (n = 53)

Excluded: Women in labour, with ruptured membranes, multiple pregnancies, smokers or any concurrent medical complications before or developing during pregnancy, such as diabetes mellitus or inflammatory diseases

Consecutive women undergoing routine 3rd trimester blood analysis and with none of the exclusion criteria (n = 30)Venous blood samples were drawn after 8 hours fast. Blood was centrifuged and plasma lipid profile (total cholesterol and triglycerides) and uric acid were measured by quantitative enzymatic assays (Sigma; St Louis, MO, USA))
Lorentzen, 1995 (n = 34)

Nulliparous women with pre-eclampsia (n = 17) attending the ultrasound screening (17–19 weeks)

Excluded: None

Normotensive healthy controls (n = 17) matched for age, BMI, parity and gestationTGs were measured after 8–10 hours fast between 17 and 19 weeks
Maseki, 1981[52] (n = 45)

Women with pre-eclampsia (n = 23) with mean gestational age 36 and SD 2 weeks

Excluded: None

Women with normal pregnancies (n = 22) with mean gestational age 35 and SD 3 weeksFasting blood was taken in the morning. Serum lipoproteins were fractionated by ultracentrifugation. TGs were measured with chemicals of reagent grade
Mikhail, 1995

Pregnant women with pre-eclampsia (n = 29) and singleton pregnancies from 28 to 42 weeks

Excluded: Women with ruptured membranes, in labour or with medical complications

Controls were recruited from the antenatal clinics (n = 46)Fasting blood samples were obtained and TG measurements were made using standardised techniques
Murai, 1997 (n = 62)

Women with singleton pregnancies and pre-eclampsia (n = 31)

Excluded: None

Women with normal pregnancies matched for nulliparity, race, maternal age at delivery (within 3 years), and duration of pregnancy (within 2 weeks) (n = 31)Non-fasting serum samples were collected during the late third trimester of pregnancy before labour or administration of antihypertensive agents or intravenous fluids. Blood samples were drawn at 36–38 weeks of gestation from asymptomatic women. Plasma TGs were quantified in matched women using a microtitre-plate modification of the Sigma triglycerides diagnostic kit
Ozan, 1997 (n = 59)

Women with pre-eclampsia (n = 39)

Excluded: Women with a history of antihypertensive medication, cardiac disorder, diabetes mellitus, hyperlipidaemia, hepatic or renal disorder, the smokers and the drinkers

Women with uncomplicated pregnancies (n = 20)Fasting serum TG level measurements were obtained at admission to hospital. Serum triglyceride levels were determined by enzymatic-spectrophotometric methods (BioSystems, American Biosystems, Inc., Roanoke, VA, USA)
Powers, 1998 (n = 54)

Women with pre-eclampsia (n = 21)

Excluded: None

Women with uncomplicated pregnancy with no medical problems (n = 21)Plasma samples were obtained ≥6 hours after each woman's most recent meal and all measurements were performed with appropriate diagnostic kits supplied by Sigma Chemical Co
Raijmakers, 2004 (n = 64)Women with pre-eclampsia (n = 40) with a median gestational age of 30 weeks and range from 24 to 36 weeksWomen with uncomplicated pregnancies matched for gestational age (n = 24) with a median gestational age of 31 weeks and range from 30 to 32 weeksFasting status is unreported or technique of measurement
Sahu, 2009 (n = 60)

Primigravida women with pre-eclampsia (n = 30) attending the hospital in their third trimester

Excluded: Women with diabetes mellitus with or without treatment, obesity, severe anaemia, eclampsia or women suffering from any other systemic or endocrine disorder

Primigravida women matched for age in their third trimester (n = 30)Fasting samples were analysed by enzymatic colorimetric methods in the autoanalyser (Dimension AR, Dade Behring Limited, Milton Keynes, UK)
Schjetlein, 1999 (n = 297)

Women with pre-eclampsia (n = 200) with a mean gestational age of 35.6 weeks and range from 27 to 40 weeks

Excluded: Women with essential hypertension, diabetes, nephrotic syndrome or thyrotoxicosis

Women with uncomplicated pregnancies (n = 97) with a mean gestational age of 36.3 weeks and rangefrom 24 to 42 weeksFasting samples were analysed for TG levels with conventional routine methods
Spaan, 2010 (n = 51)

Caucasian primiparous women with pre-eclampsia (n = 22)

Excluded: Women with pre-existent hypertension, diabetes mellitus, renal disease, current cancer therapy or chronic use of corticosteroid medication

Caucasian primiparous women with uncomplicated pregnancies (n = 29)Fasting samples were analysed by standard automated laboratory techniques (Beckman Coulter LX20 PRO, Fullerton, CA, USA) 23 years after pregnancy
Vanderjagt, 2004 (n = 173)

Women with pre-eclampsia (n = 43) at a mean gestational age of 35.7 and a standard error of 4 weeks

Excluded: None

Pregnant women with no obvious medical problems (n = 143) at a mean gestational age of 31.6 and a standard error of 7 weeksTG concentration was determined by the method of Spayd and co-workers[51] with a Vitros analyzer clinical chemistry slide and a Vitros 950 analyzer (Ortho Diagnostics, Rochester, NY, USA)
Ware-Jauregui, 1999 (n = 304)

Women with pre-eclampsia (n = 125)

Excluded: Women with chronic hypertension and postpartum

Women with uncomplicated pregnancies matched for gestational and maternal age (n = 179)TG concentrations were mostly fasting (94%) and measured enzymatically employing assays standardised by the Lipid Standardization Programme of the Centres for Disease Control and Prevention, Atlanta, GA, USA
Williams, 2003 (n = 359)

Women in their postpartum with pre-eclampsia (n = 173)

Excluded: Women with chronic hypertension

Women with uncomplicated pregnancies delivered within 2 hours of the cases (n = 186)TG concentrations were measured 12–72 hours postpartum enzymatically using assays standardised by the Lipid Standardization Programme of the Centres for Disease Control and Prevention, Atlanta, GA, USA
Table 2. Characteristics of the cohort studies
Study, yearPopulationTriglyceride (TG) testOutcomeStudy Design/Follow up
Clausen, 2001 (n = 2157)

Pregnant women at their ultrasound scan (17–19 weeks)

Excluded: Women with twin pregnancies

Triglycerides were measured at the time of recruitment in a non-fasting state (17–19 weeks) and allowed to coagulate before centrifugation at 400 g for 10 minutes. The serum samples were transferred on ice to a −708°C freezer within 140 minutes after venepunctureWomen were observed routinely for pre-eclampsia, pregnancy-induced hypertension according to early or late onset (before or after 37 weeks)

Prospective cohort study

Follow up: 6.7% of women delivered elsewhere

Enquobahrie, 2004 (n = 567)

Pregnant women attending prenatal care clinic before 16 weeks of gestation

Excluded: Women with chronic hypertension, diabetes mellitus and spontaneous or induced abortions

Maternal nonfasting samples, collected at an average of 13 weeks gestation. Maternal plasma TG concentrations were measured enzymatically using assays standardised by the Lipid Standardization Programme of the Centres for Disease Control and Prevention (Atlanta, GA, USA)Women were observed routinely for pre-eclampsia, pregnancy-induced hypertension according to early or late onset (before or after 37 weeks)

Prospective cohort study

Follow up: n = 45 of women delivered elsewhere, moved or their medical records were missing

Setareh, 2009 (n = 343)

Pregnant women referred to antenatal care before the week 16

Excluded: Women with diabetes, chronic hypertension, previous obstetric complications or other systemic disease

Fasting blood samples were taken on week 16 for TG measurement. Enzymatic colorimetric test was used to define TGIn follow up, blood pressure of both severe pre-eclampsia and control group were recorded again in week 38 of pregnancy and pre delivery. Only severe pre-eclampsia is compared with control

Prospective cohort study

Follow up: None reported

Takahashi, 2008 (n = 48)

Pregnant over 35 years of age women with ongoing gestations (>13 weeks) of single foetuses

Excluded: Women with a history of cardiovascular or kidney disease, and/or diabetes mellitus

In the first trimester (until the 13th week) and second trimester TGs were measured. The measurement of serum TG was done using the enzymatic colorimetric method on an Advia® 1650 (Bayer®) deviceWomen were observed and groups were separated into those who developed pre-eclampsia and those who did not

Prospective cohort study

Follow up: No losses

Ziaei, 2006 (n = 470)Women in their first pregnancy between 28 and 32 weeks (n = 470) Exclusion: Women with diabetes mellitus or any other endocrine or metabolic disorder, any history of cardiovascular disease and hypertension, smoking, and nonsingleton pregnancyTriglycerides were measured at 28–32 weeks of pregnancyWomen were observed once every other week until 36 weeks of gestational age. Afterward, they were checked once a week until 40 weeks of gestational age. For each woman who experienced pre-eclampsia, a non-hypertensive healthy pregnant participant delivering at term was matched for age, body mass index, educational level, family income, and occupation. Triglyceride levels from women with pre-eclampsia were compared with the matched women with normal pregnancies

Prospective cohort study

Follow up: No losses

Association between raised triglycerides and pre-eclampsia

Meta-analysis of the results of the 24 case–control studies shows that pre-eclampsia is associated with higher levels of serum triglycerides (WMD 0.78 mmol/l, 95% CI 0.60–0.96, < 0.00001) (Figure 3). In this meta-analysis, we encountered significant heterogeneity (I2 = 94%, < 0.00001). We explored the possible reasons for this heterogeneity and we identified the gestational age of triglyceride measurement as a possible factor. We therefore undertook a subgroup analysis of studies according to the gestational age and found that triglycerides were significantly higher in the third trimester compared with the second trimester or postpartum (third trimester, WMD 0.86 mmol/l, 95% CI 0.64–1.09 versus second trimester, WMD 0.23, 95% CI 0.10–0.36 and postpartum, WMD 0.41, 95% CI 0.30–0.53, < 0.00001). Meta-analysis of the five prospective cohort studies confirms the association of hypertriglyceridaemia, when measured in the second trimester, with pre-eclampsia (WMD 0.24 mmol/l, 95% CI 0.13–0.34, P < 0.0001). We encountered moderate heterogeneity in this analysis (I2 = 62%, P = 0.03). The triglyceride levels were significantly different across studies according to the fasting status of the women when the blood samples were taken (χ2 = 15.73, P < 0.00001). Our planned adjustment of our inferences for BMI was not performed, as the primary studies did not stratify the results according to BMI.


Figure 3. Forest plot showing the results of meta-analysis of studies along with calculated exact binomial confidence intervals that examine the difference in triglyceride concentrations in women with pre-eclampsia compared with normal controls. Results subgrouped according to the study design.

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  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

In this systematic review we found that hypertriglyceridaemia is associated with and precedes the onset of pre-eclampsia. We found this association mostly in case–control studies performed in the third trimester, but also in cohort studies that included women from the second trimester of pregnancy. From this study, we add epidemiological evidence supporting that hypertriglyceridaemia may be involved in the causal pathway of pre-eclampsia. This inference is justified primarily by the strength of the association found in this study for both second and third trimesters. All the included studies were consistent in suggesting this association and in only three studies (3/29) the 95% confidence intervals marginally crossed the line of the null hypothesis being true. Even so, a constellation of metabolic changes may happen that lead to pre-eclampsia, and hypertriglyceridaemia may only explain a part of this pathway. This prevents us from drawing strong conclusions about causality from this study. The temporality, though, where hypertriglyceridaemia clearly precedes the onset of pre-eclampsia, leads us to generate the hypothesis that we may be able to change the natural history of the disease if we intervene early by lowering the triglyceride levels. Before such an intervention it would be important to define the normal triglyceride levels in pregnancy and correctly identify women that could benefit most from this therapy.

A weakness, which is difficult to account for, is that the observed association may be overestimated because of the study design in case–control studies, but this was also proven in five prospective cohort studies when analysed separately. The case–control studies were significantly different between themselves, which is reflected in the high heterogeneity we encountered in this meta-analysis. This was partially explained from the different gestational age and fasting status of the targeted populations across the studies. The selection of controls varied across the studies, which introduced further heterogeneity. Potential bias is also possible in the case–control studies because the cases were not always representative of women with pre-eclampsia. The selection of controls did not include community controls and convenient hospital controls were often used. This introduces bias and in most of the studies the comparability of cases and controls was found to be poor. The cohort studies were of higher quality and their results are likely to be more reliable. Of note, is the fact that hypertriglyceridaemia may be associated with nutrition, and indeed, it was our aim also to adjust our estimates for BMI, which is a potential confounder, but the primary studies did not stratify their results according to BMI. However, BMI in women with pre-eclampsia compared with healthy women was reported and statistically tested in 12 studies. In the majority of the studies there was only weak evidence that groups were different for BMI with P-values >0.05 in 11 studies. However, the direction of the association was not different for any of the included studies and only the strength of the association differed.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References

The association between hypertriglyceridaemia and pre-eclampsia were significant in both analyses of case–control and cohort studies. The cohort design of five included studies also highlights the temporality of this association where hypertriglyceridaemia present in the second trimester preceded the onset of pre-eclampsia, which was often diagnosed in the third trimester. This is clinically attractive because measurement of triglycerides is well established in all clinical laboratories and may represent a cost-effective way of identifying at-risk pregnancies. The role of hypertriglyceridaemia in the pathogenesis of the disease and particularly potential mechanisms by which it might be modulated are potential avenues for further research.

Disclosure of interests

None to be declared.

Contribution to authorship

IDG and MV conceptualised this study. IDG, KS and MV performed the search, selected abstracts, obtained the full manuscripts and extracted the data. IDG performed the meta-analysis and wrote all versions of the manuscript. MK, AC, ST and MV critically revised the manuscript and all authors approved the final version.

Details of ethics approval

Not required.


No funding was sought for this study.




  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. References
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