Elami-Suzin, Matan

Elhayani, Asher

Mankuta, David

Vinker, Shlomo

Lipids in Health and Disease

English

PubMed

David Mankuta

Matan Elami-Suzin

Asher Elhayani

Shlomo Vinker

Springer - Publisher Connector

Lipid profile in consecutive pregnancies

Crossref

Mankuta et al. Lipids in Health and Disease 2010, 9:58
http://www.lipidworld.com/content/9/1/58
Open AccessR E S E A R C HResearchLipid profile in consecutive pregnancies
David Mankuta*1, Matan Elami-Suzin1, Asher Elhayani2 and Shlomo Vinker3
Abstract
Aim: To describe the lipid profile of women prior to, during and after pregnancy and to assess the effect of consecutive 
pregnancies on the plasma lipid profile.
Methods: Blood lipid levels of 1752 women aged 20-45 years who delivered between 1999 and 2005 were measured. 
The lipid profile included total cholesterol, LDL-C (Low density lipoprotein), HDL-C (High density lipoprotein-C), VLDL-C 
(Very low density lipoprotein) and triglycerides (TG). The measurements were classified into the following categories: 
non-pregnant state (12 months prior to conception), during the three trimesters of pregnancy and from 6 weeks to 12 
months postpartum. This profile was tested in up to three subsequent pregnancies.
Results: Total cholesterol levels overall rose during pregnancy. In the first trimester there is an average decrease of 11.4 
mg/dL in total cholesterol level (p < 0.0001) followed by an average increase of 50.5 mg/dL and 28 mg/dL in the 
second and third trimesters respectively (p < 0.0001). In the year after pregnancy, the levels return to pre- pregnancy 
levels. LDL and triglyceride levels show a similar pattern.
In contrast, HDL-C levels do not change significantly in the first trimester. The second trimester is characterized by an
average elevation of 14 mg/dL (p < 0.0001) and a decrease of 5 mg/dL in the third trimester (p = 0.03).
The average HDL-C levels of every period tested were lower in the 2nd and 3rd subsequent pregnancies.
Conclusions: There is a general increase in total cholesterol, LDL and VLDL during pregnancy. We demonstrate a 
cumulative effect of consecutive pregnancies on lowering HDL cholesterol levels. This effect may have negative 
implications on future cardiovascular health.
Introduction
Blood lipid concentrations, lipoproteins and apolipopro-
teins in the plasma increase significantly during preg-
nancy [1]. Fat storage occurs primarily during mid-
pregnancy [2,3].There is some evidence that progester-
one, which increases markedly in the second half of preg-
nancy, may act to reset the lipostat in the hypothalamus.
Hypercholesterolemia is an important cause of early
atherosclerosis [4]. Nevertheless, there is conflicting evi-
dence for an association between parity and the risk of
cardiovascular disease in women [5,6]).
LDL-C levels peak at mid-third trimester, probably as a
consequence of the hepatic effect of estradiol and proges-
terone [7]). It has been suggested that the increase in
plasma triglycerides and LDL-C patterns during preg-
nancy might be used to identify women who will develop
atherogenic changes later in life [1]).
Previous studies have reported a decline in HDL cho-
lesterol up to 10 years after the first pregnancy, indepen-
dent of weight, central adiposity and selected behavioral
changes [8].
We undertook to evaluate the lipid profile prior to, dur-
ing and post-pregnancy, in single and subsequent preg-
nancies, over a 6-year period, and to specifically examine
the effect of up to three pregnancies on the lipid profile.
Methods
The study was conducted in the Central District primary
care clinics of Clalit Health Services. This is the largest
health-management organization (HMO) in Israel, with
approximately 3.5 million clients. The Clalit Health Ser-
vices Registry database includes information collected
from a Variety of sources: primary care physician reports,
medication-use files, hospitalization records and outpa-
tient clinic records.
The electronic medical records of 1752 women aged
20-45 women who delivered between January 1, 1999 and
* Correspondence: mankutad@gmail.com
1 Hadassah University Hospital Jerusalem Israel
Full list of author information is available at the end of the article© 2010 Mankuta et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Mankuta et al. Lipids in Health and Disease 2010, 9:58
http://www.lipidworld.com/content/9/1/58
Page 2 of 4December 31, 2005 were reviewed. The women were all
in the reproductive age, i.e. 20-45 years old. Adolescents
and women over age 45 were excluded because preg-
nancy in those age groups is considered to be high risk.
All the information on chronic diseases in the study pop-
ulation was provided by their primary care physicians
based on CHPPC codes (Classification of Health Prob-
lems in Primary Care) for these diseases. Women with
chronic diseases that may affect the lipid profile were
excluded from the study. Furthermore, all the prescrip-
tions that the study population used during the period
were evaluated. Women who used a medication that
could possibly affect the lipid profile were also excluded,
as were patients with a family history of dyslipidemia.
The routine blood work for pregnant women in Israel
and most other countries usually includes a complete
blood count in the first trimester, and later syphilis and
HbsAg screening; it does not as a rule include a lipid pro-
file. Nevertheless, some physicians and patients elect to
use the opportunity to perform additional tests. Although
it is a minority of pregnant women in whom a lipid profile
is evaluated, the absolute numbers are high. It is possible
that the group requesting or being offered the test may be
more concerned or aware of blood lipid status. The meth-
ods of registry acquisition and maintenance have been
described in detail elsewhere [9].The lipid profiles
obtained were classified into the following categories:
non-pregnant state (12 months prior to conception), dur-
ing each trimester of pregnancy and from 6 weeks to 12
months post-partum. All lipid profiles of the same
woman performed during the study period were
retrieved. In general, the tests were performed following
an overnight fast, although we did not have information
on individual compliance with this requirement. The
number of tests per patient ranged from one to six tests.
The average results were analyzed with respect to each
pregnancy for the whole group. Patients who were being
treated medically for hypertension, diabetes or hypercho-
lesterolemia (total cholesterol > 200 mg/dL) were
excluded from the study.
Statistical analysis
Tests and data preparations were analyzed using SAS ver.
8.1 Statistical package (SAS Institute Inc., Cary, NC,
USA) with double sided 0.05 significance level. An inde-
pendent two-sample t-test was used. If the distribution
was too asymmetric we used the two-sample Mann-
Whitney test.
Since the analyses were performed retrospectively on
an existing database, and some women had lipid tests at
different time intervals whereas others were tested on a
single occasion, we performed separate analyses in those
groups (paired analyses and two samples independent
test, respectively). Any group sample size below 30 was
excluded from analysis.
Results
2686 test results were analyzed. Seventy-four women
(4.3%) had one pregnancy during the six-year period of
the study, 1567 (91.1%) had two pregnancies, and 79
(4.6%) had three pregnancies. The mean age of women at
delivery was 30.4 years.
Total cholesterol
Figure 1 depicts the various lipids and lipoprotein levels
during pregnancy. Total cholesterol changes during preg-
nancy: a decrease of 11.4 mg/dL in total cholesterol level
(p < 0.0001) is seen in the first trimester during the study
period. A significant average increase of 50.5 mg/dL (p <
0.0001) occurs between the first and second trimesters,
and a further increase of 28.5 mg/dL, on average,
between the second and third trimesters (p < 0.0001). In
the year after the pregnancy, the levels return to pre-
pregnancy levels. A similar pattern of total cholesterol
levels recurs in the second and third pregnancies.
LDL cholesterol
The LDL-C levels decreased non-significantly by 3.3 mg/
dL on average (p = 0.216) during the first trimester. Dur-
ing the second trimester LDL-C increases by 25.9 mg/dL
(p < 0.0001), followed by a further increase of 19.4 mg/dL
(p = 0.0097) in the third trimester. Within one year post-
partum, LDL-C returns to pre-pregnant levels and con-
tinues to decline to levels even lower than pre-pregnancy
during the second and third years post-partum.
Triglycerides
The first trimester shows an average decrease of 13.3 mg/
dL (p < 0.0001) in TG levels. The second trimester dem-
onstrates an average elevation of 64.9 mg/dL (p < 0.0001)
followed by a further increase of 52.2 mg/dL (p < 0.0001,
paired t-test) in the third trimester.
HDL cholesterol
In contrast to total and LDL cholesterol, HDL-C levels do
not change significantly in the first trimester. The second
trimester is characterized by a steep elevation of 14 mg/
dL in HDL-C levels (p < 0.0001) and a slight decrease of 5
mg/dL in the third trimester (p = 0.03). The levels plateau
and do not decline further one year after pregnancy.
Average HDL-C levels of every period tested were lower
in subsequent pregnancies (Figure 2).
Table 1 summarizes the effects of pregnancies and post
partum period on lipid/lipoprotein levels.
Discussion
Pregnancy induces significant metabolic changes. The
concentrations of lipids, lipoproteins and apolipoproteins
Mankuta et al. Lipids in Health and Disease 2010, 9:58
http://www.lipidworld.com/content/9/1/58
Page 3 of 4Figure 1 Average lipid profile during pregnancy.
	

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in the plasma increase appreciably during pregnancy. The
lipid levels are affected by maternal hormonal changes
(rise in insulin, progesterone, 17-β estradiol and Human
Placental Lactogen). Other maternal factors such as BMI
(body mass index), maternal weight gain, maternal nutri-
tion, pre-pregnancy lipid levels and various medical com-
plications of pregnancy may also have significant effects
on lipid metabolism and plasma levels [10].
Until the CARDIA study by Gunderson et al [11,12]
evidence regarding the association between parity and
the risk of cardiovascular disease in women has been
conflicting. That prospective study, among 1952 Ameri-
can women, examined lipid changes over a 10 year
period, and adjusted the results to allow for various con-
founding factors. For both white and non-white popula-
tions a decline of 3 to 4 mg/dL in HDL-C was seen during
the first pregnancy compared with nulliparous women.
Higher order births were not associated with a greater
decline in HDL cholesterol.
We assessed the influence of consecutive pregnancies
on lipid changes. In our study population the total choles-
terol generally increased during pregnancy by approxi-
mately 40% and returned to pre-pregnancy levels within
one year postpartum. We noted a slight decrease during
the first trimester, an observation described in other
studies [13,14].A possible explanation for the decrement
during the first trimester may be a decreased intake of
food due to nausea and vomiting, which characterize the
early stages of pregnancy (10).
LDL-C demonstrates a similar pattern to total choles-
terol, with an average increase of approximately 23% in
the third trimester. However, after the first year postpar-
tum, the levels of LDL-C continue to decline even below
pre-pregnancy levels.
Triglyceride levels, as also shown in other studies
[1,14], doubled in the third trimester. However, we also
demonstrated an initial decrease in TG levels in the first
trimester, a pattern not shown in previous studies [1,14].
Apparently, consecutive pregnancies do not influence
baseline (non-pregnant) TG levels. These findings are
consistent with the findings of Gunderson et al [11,12].
HDL-C levels mainly rise in the second trimester, but
begin to decline from the third trimester, reaching their
nadir one year postpartum. Interestingly, our results
Figure 2 Average HDL cholesterol levels in subsequent pregnan-
cies.
Mankuta et al. Lipids in Health and Disease 2010, 9:58
http://www.lipidworld.com/content/9/1/58
Page 4 of 4show that with each consecutive pregnancy HDL-C rises
to lesser extent, and the nadir is lower. These changes
may be a risk factor for future atherosclerosis.
This study has several limitations. The first is that it
lacks a non-pregnant control group in the same period. It
is known that aging is a significant factor affecting
changes in the lipid profile - a factor we did not analyze.
We also lack data about weight changes during this six-
year period, as well as information on the diet of the sub-
jects - factors that may affect the lipid profile [15]).
Another possible explanation for the changes we found
may be the decline in physical activity due to increased
demands of the growing family over time.
Our study has some other limitations. This is a retro-
spective study and the effect of factors such as breast
feeding and birth control pills were not available for
adjustment [10-12].We controlled the women to their
own pre-pregnancy lipid levels rather than comparing to
a nulliparous group, which would provide another per-
spective of the change in the lipid profile with age.
Our study reinforces the results of previous studies
[14,15] supporting the hypothesis that pregnancy exerts
persistent adverse effects on HDL cholesterol. We dem-
onstrate a cumulative effect of consecutive pregnancies
on lowering HDL cholesterol levels. This effect may have
negative implications on future cardiovascular health.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
DM initiated the study idea, analyzed the data, wrote the manuscript formed
the graphs and table and submitted the manuscript and is the corresponding
author, ME has contributed to the statistical analysis of the study, and the writ-
ing of the manuscript and has equal contribution to the manuscript as the first
author. AE contributed in the database establishment and data retrieval while
SV came with the idea of the study with DM and performed the data retrieval
and analysis. All authors have read and approved the final manuscript
Author Details
1Hadassah University Hospital Jerusalem Israel, 2Meir Medical Center Kefar 
Saba, Israel and 3Department of Family Medicine, Sackler Faculty of Medicine, 
Tel Aviv University, Tel Aviv, Israel
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doi: 10.1186/1476-511X-9-58
Cite this article as: Mankuta et al., Lipid profile in consecutive pregnancies 
Lipids in Health and Disease 2010, 9:58
Received: 25 March 2010 Accepted: 5 June 2010 
Published: 5 June 2010
This article is available from: http://www.lipidworld.com/content/9/1/58© 2010 Mankut  et al; licensee BioMed Central Ltd. is an Open Access articl  distributed un er the ter s f the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Lipids in H alth nd Di ease 2010, 9:58
Table 1: Summary lipid profile during pregnancy
One year after 3 
subsequent pregnancies
3rd trimester 2nd trimester 1st trimester
Total cholesterol    
LDL cholesterol    
HDL cholesterol    
Triglycerides    N/A


Bilianou HG: Influence of aging and menopause on lipids and lipoproteins in women. Angiology 2008, 59(2 Suppl):54S-7S. doi: 10.1186/1476-511X-9-58 Cite this article as: Mankuta et al., Lipid profile in consecutive pregnancies

Do long-term HDL-C declines associated with a first birth vary by apo E phenotype? The Coronary Artery Risk Development in Young Adults (CARDIA) study. J Womens Health (Larchmt)

E: Longitudinal study on lipoprotein profile, high density lipoprotein subclass and postheparin lipases during gestation in women.

Fat morphology and adiposity in pregnancy.

Hyperlipidemia and premature arteriosclerosis. Lipids

KP: Correlation of hormones with lipid and lipoprotein levels during normal pregnancy and postpartum.

Long-term plasma lipid changes associated with a first birth: the Coronary Artery Risk Development in Young Adults study.

Milia S: Lipoprotein metabolism during normal pregnancy.

Mortality in women in relation to their childbearing history. BMJ

Ohlin A: Pregnancy as a risk factor for obesity.lessons from the Stockholm Pregnancy and Weight Development Study. Obes Res 1995, 3(Suppl 2):267s-275s.

Peterburg Y: Prevalence of selected chronic diseases in Israel. Isr Med Assoc J

Plasma lipoproteins including high density lipoprotein subfractions during normal pregnancy. Obstet Gynecol

S: Development of overweight associated with childbearing depends on smoking habit: The Coronary Artery Risk Development in Young Adults (CARDIA) Study. Obes Res

Shofer FS: Reproductive history and coronary heart disease risk in women. Epidemiol Rev

Staszewski A: Reference ranges of lipids and apolipoproteins in pregnancy.

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Lipid profile in consecutive pregnancies

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