Metabolic Syndrome in Normal and Complicated Pregnancies

Abstract

Background:

The aim of our study was to elucidate the association of the metabolic syndrome with the risk of unsuccessful pregnancy.

Methods:

This was a retrospective observational study conducted at Markusovszky Teaching Hospital, Szombathely, Hungary, a tertiary health care center. During the study period of 2007–2011 (5 years), 7373 pregnancies were followed. Pregnant women who were suffering from metabolic syndrome in the first trimester of gestation during the study period were compared to all other pregnant women without the syndrome. Retrospectively, 219 (2.9%) patients met the criteria of metabolic syndrome during the first trimester. Our goal was to evaluate the prevalence of the metabolic syndrome in normal pregnancies and in those complicated by either premature birth, or intrauterine growth retardation (IUGR), pregnancy-induced hypertension, and preeclampsia.

Results:

The rate of preterm birth was 15.2% [32/219 in the metabolic syndrome group vs. 11.1% (p=0.051) in the control group]. Within the affected group, 40 pregnancies were complicated with IUGR (18.4%) versus 3.3%, in the unaffected group (p<0.001). In 58 cases, we observed preeclampsia during pregnancy [26.7% vs. 5.2% (p<0.001)] in the control group. Among the patients affected by the metabolic syndrome, 83 patients (38.2%) had more then one pregnancy complication during pregnancy, and only 59 cases (27.2%) had no adverse events during pregnancy and delivery (p<0.001).

Conclusions:

Our study demonstrated a higher rate of complicated pregnancies in association with metabolic syndrome compared to the control group.

Introduction

I n 1998, the World Health Organization (WHO) proposed the term “metabolic syndrome,”¹ formerly known as insulin resistance syndrome, to define the combination of diseases and risk factors accompanying type 2 diabetes mellitus (T2DM)—mainly obesity, hypertension, and dyslipidemia. T2DM is becoming extremely common: Its worldwide prevalence is predicted to reach 5%–7% by 2025.^2,3 About 3%–15% of women develop gestational diabetes mellitus (GDM) during pregnancy. Although many factors are related to the risk, including previous occurrence of GDM, age parity, family history of diabetes, and dyslipidemia in pregnancy, obesity acts as an independent risk factor for developing GDM, with a risk of about 20%.⁴

The normal physiology of pregnancy includes several components of the metabolic syndrome—a relative degree of insulin resistance, accumulation of fat tissue, hyperlipidemia, and an upregulation of the inflammatory cascade.^5,6 Obviously, not all pregnant women develop pregnancy-induced metabolic conditions, but a considerable proportion does.⁷ Approximately, 6%–8% of pregnant women develop GDM and about 3%–5% manifest pregnancy-induced hypertension. Recognition of the metabolic syndrome may lead to improved prevention of some pregnancy complications.⁸ The role of maternal medical or nutritional interventions in reducing the future risk of metabolic syndrome and its components in the mother and baby requires further research.^9

–13

The aim of this study was to evaluate the prevalence of the metabolic syndrome in normal pregnancies and in those complicated by either preterm births, or intrauterine growth retardation (IUGR), pregnancy-induced hypertension, and preeclampsia.

Materials and Methods

This was a retrospective study in the Markusovszky Teaching Hospital, Szombathely, Hungary, in a tertiary health care center. During the study period of 2007–2011 (5 years), we followed 7373 pregnancies. Retrospectively, 297 (2.9%) patients met the criteria of metabolic syndrome at any time during the first 12 weeks of pregnancy.

The constituents of the metabolic syndrome were defined as follows. Hypertension was defined as >140 mmHg for systolic and/or ≥90 mmHg for diastolic blood pressure, where blood pressure values were the means of the last two blood pressure readings. Diabetes mellitus or impaired glucose tolerance was diagnosed in patients with fasting serum glucose more than 6 mmol/L, or previously diagnosed T2DM. Fasting lipid values were examined in the morning. Dyslipidemia was defined as one or any combinations of the following: Total cholesterol >5.2 mol/L (hypercholesterolemia), triglycerides >1.7 mol/L (hypertrigliceridemia), and high-density lipoprotein cholesterol (HDL-C) <1.0 mol/L (HDL hypercholesterolemia). Overweight and obesity were defined as abnormal or excessive fat accumulations, according to definitions of WHO and the National Institutes of Health—overweight as a body mass index (BMI) of 25–29.9 kg/m², and obesity as a BMI of ≥30 kg/m². According to the study protocol, patients with metabolic syndrome fulfilled three criteria out of the aforementioned four major components of metabolic syndrome.

Preeclampsia is hypertension in association with significant amounts of protein in the urine (≥300 mg/24 h collection). Any child born before the end of the 37^th week of gestation as calculated from the first day of the woman's last menstrual period and confirmed by ultrasound was considered preterm birth. IUGR was defined as birth weight lower than the 10th percentile predicted for gestational age.

The pregnant women suffering from metabolic syndrome in the first trimester of gestation during the study period were compared to all other pregnant subjects without the syndrome. In the case of diabetes or hypertension, the medications followed international recommendations. Antenatal care, delivery, and postpartum visit were performed in the same institution, therefore it was possible to obtain exact data for all 7369 patients from the first visit of the pregnancy to the end of the postpartum period. According to the study protocol in the control group, those patients did not meet more than one criterion of metabolic syndrome; however, the lipid profile was available in only 6797 patients out of the total control study group of 7373 patients. These 576 control patients with unknown lipoid profile had normal blood pressure, normal BMI, and normal serum fasting glucose levels.

Statistical analysis of clinical data was performed in SPSS for Windows v. 11.5. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated by the univariate binary logistic regression method. All subjects with metabolic syndrome were compared to those lacking the syndrome. In a subanalysis, subjects with each specific obstetrical complication were compared to all other subjects who did not have that specific obstetrical complication. A p value<0.05 was considered statistically significant. ORs and 95% CI values were also calculated.

Results

During the study period from January 1, 2007, to December 31, 2011, 7373 pregnancies were managed in our institution. A total of 219 (2.9%) of them were found retrospectively to suffer from the metabolic syndrome at any time during the first 12 weeks of pregnancy.

The subsequent data of these pregnant women were compared to those of the 7154 patients not exhibiting the syndrome during the study period. Major characteristics of patients in the study (with metabolic syndrome) and in the control group (without metabolic syndrome) at the time of the first weeks of pregnancy are shown in Table 1. In the affected group, the rate of preterm birth was 15.2% (32/219) in contrast to the figure found in the rest of pregnant mothers: 11.1% (791/7154; OR=1.52; 95% CI 0.996–2.33; p=0.051). As many as 15 of the total of 32 preterm deliveries (46%) were elective, in contrast to the rest of patients, with only 31 elective deliveries among all premature ones (3.9%; 28/791). The induced preterm deliveries were mostly (9 out of 15 cases) associated with pregnancy-induced hypertension or preeclampsia. During the study period there were 40 pregnancies complicated with IUGR (18.4%) in the affected group versus the unaffected group—3.3% (236/7154) (OR=6.38; 95% CI 4.24–9.61; p<0.001). In the affected group, preeclampsia was observed in 58 cases during pregnancy (26.7%), whereas in the unaffected group it was only 5.2% (369/7142); (OR=7.93; 95% CI 5.54–11.33; p<0.001).

Table 1.

Major Characteristics of Patients in the Study (with Metabolic Syndrome) and in the Control Group (Without Metabolic Syndrome)

Characteristics		Study group with metabolic syndrome	Control group without metabolic syndrome
Number of cases	Total	219 (100%)	7154 (100%)
	<20 years	7 (3.2%)	279 (3.9%)
	20–25 years	20 (9.2%)	858 (12.0%)
	26–30 years	65 (30.0%)	2424 (33.9%)
	31–35 years	82 (36.9%)	2599 (36.3%)
	36–40 years	34 (15.7%)	844 (11.8%)
	>40 years	11 (5.1%)	150 (2.1%)
Average age (years)	30.3	36.0	29.8
	Mean±SD	Mean±SD	Mean±SD
Blood pressure
Systolic	127±37 mmHg	155±32 mmHg	118±41 mmHg
Diastolic	82±17	96.2±20.1 mmHg	78±318.7 mmHg
Total cholesterol^a,d	4.7±1.4 mmol/L	6.9±1.7 mmol/L	4.1±1.1 mmol/L^d
Triglyceride^b,d	1.7±mmol/L	2.2±0.27 mmol/L	1.2±0.78 mmol/L^d
HDL-C^c,d	410±55 U/L	475±37 U/L	380±72 U/L^d
Body mass index	23.7±6.7	32.7±3.8	20.7±1.7

Reference fasting values were: ^a3.9–5.2 mmol/L for serum total cholesterol levels, ^b0.5–2.3 mmol/L for serum triglyceride levels, and ^c230–460 U/L for serum HDL-C (high-density lipoprotein) levels.

In case of serum cholesterol, triglyceride, and HDL cholesterol data, the control group consisted of 6377 patients. The lipoid profile of 775 control patients was unknown.

SD, standard deviation.

Within the group suffering from metabolic syndrome, there were 83 patients (38.2%) who have had more then one pregnancy complication during of their pregnancy, whereas only 59 (27.2%) of this group were symptom-free during pregnancy and delivery (OR=3.11; 95% CI 2.27–4.26; p<0.001). In the group of patients without metabolic syndrome symptoms in the first trimester (7154 cases), there was a significant proportion (74.1%, 5298 patients) of mothers who carried out of their pregnancies without any complications (Table 2).

Table 2.

Outcomes According to the Presence or Absence of the Metabolic Syndrome in the Population Studied

Characteristics	With metabolic syndrome, number of cases: 219	Without metabolic syndrome, number of cases: 7154	OR [95% CI]
Preterm birth	15.2%	11.1%;	1.52
	32^a/219	791/7154	[0.996–2.33] p=0.051
IUGR	18.4%;	3.3%;	6.38
	40 /219	236/7154	[4.24–9.61 p<0.001]
Preeclampsia	26.7%;	5.2%;	7.93
	58/219	369/7154	[5.54–11.33] p<0.001
Pregnancy complications ≥2	38.2%	17.0%	3.11
	83/219	1219/7154	[2.27–4.26] p<0.001
Symptom-free pregnancy	27.2%	74.1%	0.132
	59/219	5298/7154	[0.09–0.18] p<0.001

15 of 32 induced preterm delivery.

OR, odds ratio; CI, confidence interval; IUGR, intrauterine growth retardation.

Discussion

The aim of our study was to elucidate the association of the metabolic syndrome with the risk of an unsuccessful pregnancy. Our study demonstrated a higher rate of complicated pregnancies in association with metabolic syndrome compared to the control group. The worldwide rise in prevalence of obesity has led to the WHO declaration that “obesity is a major killer disease of the millennium on par with the HIV and malnutrition.”^14

–17

Pregnancy induces a milieu that is similar to, but not identical with, the metabolic syndrome. In women with the metabolic syndrome or its components, pregnancy can exacerbate the situation, leading to worsened hyperglycemia, dyslipidemia, and hypertension. This effect can have serious consequences for the development of the fetus and probably increases the risk of future metabolic and cardiovascular disorders for both the mother and the infant.^18

–22

Although dyslipidemia is known to cause endothelial dysfunction in the metabolic syndrome,^23,24 its role in the pathogenesis of pregnancy-induced hypertension or preeclampsia is unknown. It may be suggested that hyperlipidemia contributes to the genesis of preeclampsia by causing endothelial dysfunction via direct injury to maternal endothelium or sensitization of the endothelium to placenta-derived endothelium-damaging factors or both.²⁵

Low birth weight is associated with the metabolic syndrome. The mother's high blood pressure during pregnancy may be associated with low birth weight. The risk of pregnancy-induced hypertension or preeclampsia is significantly greater if the mother was overweight in early pregnancy as assessed by BMI (≥25%). Studies suggest a two- to three-fold increased risk for preeclampsia at a BMI of ≥30 kg/m².²⁵

Current evidence suggests that obesity occurring within the metabolic syndrome may be associated with induced, but not with spontaneous, preterm delivery. Smith et al.²⁶ reported that among nulliparous women, the risk of spontaneous preterm labor decreased whereas the risk of requiring elective preterm delivery increased with increasing BMI. Bhattacharya et al.²⁷ also reported that the frequency of induced labor increased with increasing BMI, the OR being lowest in underweight women (BMI of <2 kg/ m² (OR=0.8; 95% CI 0.8–0.9) and highest in the morbidly obese (BMI of ≥35 kg/m² (OR=1.8; 95% CI 1.3–2.5).

The nature and type of type of metabolic syndrome-related pregnancy complications were such that the international medical community (WHO and International Diabetes Federation) set forth the St. Vincent's declaration of 1989; one of its aims was to achieve similar pregnancy outcomes in diabetic and nondiabetic women.²⁸ The metabolic syndrome may play an important role in the unfavorable outcome of pregnancy because it induces a proinflammatory and prothrombotic state.²⁹ Treatment options using pharmacological or surgical means are contraindicated during pregnancy. However, increased physical activity in patients with a sedentary lifestyle and the choice of healthy food rather than fast foods may result in a better pregnancy outcome for both mother and child.^30,31 Some authors suggest that in the case of metabolic syndrome low-molecular-weight heparin therapy given from the time of conception exerts a favorable effect.¹⁷

In summary, this study demonstrates an incremental increase in maternal and perinatal risks associated with metabolic syndrome, also existing in the group of pregnant women with other complications, such as preeclampsia, IUGR, and preterm birth, suggesting that these pathological conditions are linked. Our data also suggest that the combined presence of these obstetric complications can be expected. Our results suggest that if a woman suffers from metabolic syndrome before planning her pregnancy, she should employ both diet and exercise prior to and during pregnancy to reduce her body weight so as to give her better hope for a successful pregnancy and delivery. Further studies are required to confirm our findings.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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