Metabolic syndrome (MetS) is defined as a combination of central abdominal (visceral) obesity, glucose intolerance, insulin resistance, dyslipidemia and hypertension (Mohsenzadeh-Ledari et al, 2019). This syndrome is a cluster of physiological abnormalities that accelerate the risk of type 2 diabetes, atherosclerotic cardiovascular disease (Niyaty et al, 2020), some cancers, and chronic kidney disease in the adult population (Grieger et al, 2018).
The prevalence of MetS has significantly increased throughout the world over the recent years (Lee et al, 2018). Based on the results of a meta-analysis study in Iran, the prevalence of MetS was 25% its prevalence in men (26.9%) was lower than in women (35.7%) (Ostovar et al, 2017). The prevalence of MetS has increased because of the increased prevalence of obesity (O'Neill and O'Driscoll, 2015).
Despite the increasing prevalence of MetS worldwide and consequently an increased prevalence during pregnancy, there is still no established definition for MetS in pregnancy, as its diagnostic criteria overlap with the physiological changes in pregnancy (Tavares et al, 2015). Studies that have assessed metabolic components in pregnancy have generally used definitions of MetS for the adult population (Grieger et al, 2018).
In women with MetS or its components, pregnancy can lead to an exacerbation in the condition, leading to increased rates in hyperglycemia, dyslipidemia and high-blood pressure (Horvath et al, 2013). Maternal obesity, gestational diabetes and pre-eclampsia increase uterine stress, leading to an increase in the undesirable outcomes of birth (Ryckman et al, 2013). Therefore, the risk of macrosomia, hypoglycemia, preterm labour, intrauterine growth retardation, and jaundice increases in newborns (Sourinejad et al, 2019). On the other hand, inflammation and stress oxidative may be associated with poor pregnancy outcomes (Sauder et al, 2019) and all the parameters included in the diagnosis of MetS including dyslipidemia are associated with a low-grade inflammation state. Lipid peroxides and inflammation are toxic compounds that have the potential to damage endothelial cells and may be associated with increased risk of low birth weight (Niyaty et al, 2020).
Although there are few studies on MetS during pregnancy, and its effect on developing fetus and newborns, the results of the studies focusing on individual components of MetS indicate that these components may have adverse effects on neonatal outcomes. A study suggested an association between maternal lipid profile and neonatal anthropometric indices (Sourinejad et al, 2019). Mudd et al indicated that high density lipoprotein (HDL) and triglyceride (TG) levels were related to birth weight among overweight and obese women, while birth weight was related to TG among women with normal weight (Mudd et al, 2015). In addition, a study has shown that gestational diabetes or impaired glucose tolerance tests were associated with birth weight and neonatal outcomes (Ghosh and Ghosh, 2013). High-blood pressure is also a factor reducing the blood flow of the placenta, limiting intrauterine growth, and increasing the risk of low birth weight infant (Sivakumar et al, 2007).
Considering the lack of confirmatory evidence on the association between maternal MetS and neonatal anthropometric indices, especially in Iran, we aimed to assess MetS and its components in the first trimester of pregnancy and determine their associations with weight and height of the infant.
Methods
This prospective cohort study was carried out on 455 pregnant women in Tehran in 2016–2017. Pregnant women attending Nilou Laboratory (a medical laboratory in Tehran, Iran) for their routine prenatal tests were approached by the first author, the eligible pregnant women were identified, and they were informed about the research and its purpose, the research implementing method, and the benefits of conducting this research. Then, after taking a written consent and emphasis on the confidentiality of the information, individuals were assigned to the study.
Convenience sampling was used and all pregnant women who met the inclusion criteria were enrolled in the study. This research was conducted after the approval of the ethics committee in medical research with the code of ethics IR.TMU.REC.1395.392. All study related tests were performed free of charge.
The inclusion criteria of the study included gestational age less than 14 weeks, Iranian citizenship, resident of Tehran, the absence of chronic diseases, lack of verbal, auditory, or mental problems preventing communication with the researcher, lack of history of alcohol consumption, drug abuse, and psychiatric drugs, lack of certain diets, such as vegetarianism, and the age range of 18–45 years. It should be mentioned that Iranian citizenship was one of the inclusion criteria because speaking Persian was required to communicate properly with the participants, and also for ruling out any ethnic issues as confounders. Also, as vegetarian diet could act as a confounding factor in the relationship between maternal MetS and neonatal anthropometric indices, vegetarian women were excluded from the study.
In this study, gestational age in all participants was estimated using the first day of the last menstrual period (LMP), then the gestational age was matched and confirmed with the first trimester ultrasound performed. After entering the study, a demographic/obstetric questionnaire was completed through a face-to-face interview with the participant.
In addition to the routine first trimester of pregnancy tests, fasting blood glucose (FBS), HDL-Cholesterol and TG levels were measured immediately. Weight, height and blood pressure were also measured in an examination room in the laboratory. Systolic and diastolic blood pressures (BP) were measured after 15 minutes of the mother being in a sitting position, then again after 10 minutes, and the mean of the two measurements was recorded as the blood pressure.
As there is no definition for MetS in pregnancy, the MetS Diagnosis Criteria of Adult Treatment Panel III (ATP III) report of the National Cholesterol Education Program (NCEP) were modified in which the presence of three or more of the following criteria sets the diagnosis of MetS: BMI>30 kg/m2 (instead of central obesity or waist circumference >88 cm in NCEP-ATP III criteria), triglycerides >150 mg/dl, HDL-Cholesterol<50 mg/dl, systolic BP>130, diastolic BP>85 mmHg, and/or fasting blood glucose (FBS) >92 mg/dl (instead of FBS>105 mg/dl in NCEP-ATP III criteria). Since waist circumference naturally increases in pregnancy and thus it is inapplicable in this study, BMI>30 kg/m2 was used instead of waist circumference. Thus, the MetS diagnosis in pregnancy was based on the presence of three or more of the following criteria: BMI≥30 kg/m2, TG≥150 mg/dl, BP≥130.85 mm/Hg, FBS≥92 mg/dl, and HDL<50 mg/dl. Mothers underwent routine prenatal care until the end of pregnancy. After birth, the baby's weight and height data were collected from the baby's birth certificate. Furthermore, the statistical analysis was performed using SPSS software (version 21). Also, data were analysed using descriptive and analytical tests (Independent t-test, Pearson Correlation, and Linear Regression). P-value<0.05 was considered statistically significant.
Results
A total of 455 pregnant women were studied in this research. The mean age of the participating mothers was 30±4.6 years old. The majority of participants had a bachelor's degree (36.7%) and 71.6% of them were housewives (Table 1).
Table 1. Characteristics of the mothers and their newborns, participating in the study (n=455)
| Variable | Mean±SD | Number (%) |
|---|---|---|
| Age (yr) | 30±4.6 | - |
| Marital age (yr) | 23±4.4 | - |
| Age at first delivery(yr) | 26±4.5 | - |
| Gestational age at enrolment (week) | 12±0.59 | - |
| Gestational age at neonatal birth (week) | 38±1.39 | - |
| Neonatal Birth weight (gr) | 3172±444.4 | - |
| Neonatal height (cm) | 50±2.5 | - |
| Neonatal gender | ||
| Boy | - | 232 (51) |
| Girl | - | 223 (49) |
| Maternal education | ||
| Under diploma | - | 114 (25.1) |
| Diploma | - | 131 (28.8) |
| Bachelor | - | 167 (36.7) |
| Master's degree | - | 32 (7) |
| PhD | - | 9 (2) |
| Occupation | ||
| Housewife | - | 326 (71.6) |
| Employee | - | 102 (22.4) |
| Others | - | 27 (5.9) |
In total, the prevalence of MetS among pregnant women was determined as 5.9% (27 individuals), using modified ATPIII criteria. The highest prevalence of MetS components was related to low HDL (69.2%). Also, 80.9% of mothers had undergone caesarean section and 19.1% of them had normal vaginal birth (Table 1).
According to the independent t-test performed, there was a significant relationship between the first trimester of pregnancy blood pressure, and birth weight (p-value: 0.041); mothers with higher blood pressure in the first trimester of pregnancy gave birth to neonates with less weight. There were no significant relationships between the other components of MetS, or MetS itself and weight and height of the infant (Table 2).
Table 2. The relationship between metabolic syndrome components in the first trimester of pregnancy and weight and height of the newborns
| Variable | Birth weight (Mean±SD) | p-value (Independent samples t-test) | Birth height (Mean ±SD) | p-value (Independent samples t-test) |
|---|---|---|---|---|
| Pre-pregnancy BMI | 0.56 | 0.85 | ||
| ≥30 kg/m2 | 3216±495.93 | 50±1.6 | ||
| ≤30 kg/m2 | 3167±438 | 50±6.2 | ||
| FBS in the first trimester of pregnancy | 0.86 | 0.46 | ||
| ≥92 mg/dl | 3190±470.33 | 50±2.46 | ||
| ≤92 mg/dl | 3170±442 | 50±2.53 | ||
| TG in the first trimester of pregnancy | 0.074 | 0.91 | ||
| ≥150 mg/dl | 3212±597 | 50±3.30 | ||
| ≤150 mg/dl | 3163±398 | 50±2.30 | ||
| BP in the first trimester of pregnancy | 0.04* | 0.065 | ||
| BP≥130/85 mm Hg | 2895±493 | 48±2.8 | ||
| BP≤130/85 mm Hg | 3181±440.57 | 50±2.5 | ||
| HDL in the first trimester of pregnancy | 0.47 | 0.76 | ||
| HDL≤50 mg/dl | 3187.83±449.50 | 50±2.5 | ||
| HDL≥50 mg/dl | 3134.50±434.70 | 50±2.4 | ||
| Metabolic syndrome | 0.13 | 0.12 | ||
| Yes | 3001.6±590.76 | 49±3.24 | ||
| No | 3183±432.21 | 50±2.47 |
Pearson correlation coefficient test showed that, there is a positive and significant correlation between TG in the first trimester of pregnancy and birth weight (r: 0.94, p-value: 0.044). Mothers with higher TG gave birth to newborns with more weight (Table 3).
Table 3. The relationship between metabolic syndrome components in the first trimester of pregnancy and weight and height of newborns (Pearson correlation)
| Variable | Birth weight | Birth height | ||
|---|---|---|---|---|
| r | p-value | r | p-value | |
| BMI | 0.067 | 0.154 | 0.089 | 0.058 |
| FBS | 0.077 | 0.10 | 0.057 | 0.228 |
| TG | 0.094 | 0.044* | -0.006 | 0.903 |
| HDL | 0.030 | 0.517 | 0.031 | 0.511 |
| Systolic blood pressure | 0.014 | 0.759 | -0.001 | 0.98 |
| Diastolic blood pressure | 0.074 | 0.114 | 0.012 | 0.795 |
For further evaluation of the relationships between first trimester MetS and its components, and birth weight and height, linear regression analysis was performed; entering potentially effective factors on birth weight and height, along with these components in the model. Linear regression analysis showed that there were significant relationships between FBS, BMI, gestational age at birth, and MetS, with birth weight, which means mothers with higher FBS, and BMI gave birth to babies with higher weight, and mothers with MetS in the first trimester of pregnancy, had babies with lower birth weight. Also, mothers who took folic acid had babies with higher birth height. Moreover, there was a significant direct relationship between gestational age at birth and birth height (Table 4).
Table 4. Factors affecting weight and height at birth in the study population (linear regression analysis)
| Variable | Birth height | Birth weight | ||
|---|---|---|---|---|
| Beta | p-value | Beta | p-value | |
| Maternal age | 0.039 | 0.435 | 0.043 | 0.352 |
| Gravida | -0.035 | 0.491 | -0.036 | 0.445 |
| Folic acid consumption | 0.1 | 0.036* | 0.012 | 0.786 |
| Calcium consumption | 0.07 | 0.207 | 0.041 | 0.426 |
| Multivitamin consumption | 0.058 | 0.243 | 0.072 | 0.119 |
| Iron | -0.043 | 0.408 | -0.023 | 0.641 |
| FBS | 0.034 | 0.517 | 0.100 | 0.038* |
| TG | 0.031 | 0.535 | 0.092 | 0.053 |
| HDL | 0.048 | 0.324 | -0.039 | 0.389 |
| Gestational age | 0.230 | <0.001 | 0.0405 | <0.001 |
| BMI in the first trimester of pregnancy | 0.095 | 0.068 | 0.139 | 0.004* |
| Metabolic syndrome | -0.089 | 0.099 | -0.122 | 0.015* |
| Gestational diabetes | -0.036 | 0.451 | -0.032 | 0.484 |
Discussion
This cohort study was conducted on 455 Iranian pregnant women to determine the effect of MetS and its components at the beginning of pregnancy on anthropometric indices of newborns.
The prevalence of metabolic syndrome
In this study, the prevalence of MetS was 5.9%. Although there have been very limited studies on the MetS in pregnancy, in a study conducted in Brazil, the prevalence of MetS in pregnancy was reported to be 20% in the mild hyperglycemia group, 23.5% in the gestational diabetes group, and 36.4% in the diabetes group (Negrato et al, 2008). In addition, the prevalence of MetS in the middle of pregnancy was reported as 6.2% by Sourinejad et al (2016). In a study conducted by Bartha et al (2008), one-third of women with pre-term hypertension, as well as 10% of women with late-onset diabetes, were diagnosed with metabolic syndrome. Since different diagnostic criteria have been used by researchers in the definition of MetS, its prevalence has been highlighted in many studies. These different values are due to the heterogeneity of different populations and the time of diagnosis of MetS in pregnancy.
Components of metabolic syndrome and birth weight
The present study found that in the first trimester of pregnancy, there was a relationship between high-blood pressure and the baby's weight; mothers with higher blood pressure had newborns with lower birth weight. In general, women with hypertension may have an inadequate vascular response and may suffer from a defect in endothelial wall, and also abnormal placentation; on the other hand, gestational hypertension, independent of maternal obesity and metabolic disorders, is associated with insulin resistance and dyslipidemia (Niyaty et al, 2020). Similarly, the results of a study conducted by Chatzi et al (2009) showed that the risk of low birth weight was increased in women with MetS, and among the MetS components, hypertension was the most important risk factor. Himmelmann et al (1994) suggested that newborns with hypertensive mothers had lower birth weights and there was a negative correlation between maternal hypertension in pregnancy and child weight. However, in the study by Aleem Arshad et al (2011), pregnancy induced hypertension had no significant effect on birth weight.
In this study, there was a positive correlation between maternal serum TG levels and the weight of the newborn. This finding is consistent with the results of some other studies (Emet et al, 2013; Whyte et al, 2013; Hwang et al, 2015). In a study conducted by Vrijkotte et al (2011), there was a significant relationship between high levels of TG in early pregnancy and higher birth weight. Jin et al (2016) also reported that in the third trimester, each unit increase in TG concentration is associated with increased risk of gestational diabetes, pre-eclampsia, large for gestational age (LGA), macrosomia, and lower risk of small for gestational age (SGA). The results of these studies are in agreement with the results of the present study and it can be concluded that maternal TG level is an independent predictor of neonatal birth weight. Since maternal TG cannot cross through the placenta, the relationship between maternal TG levels and birth weight is confusing. In the placenta, hydrolysis of TGs to free fatty acids by placental lipases allows them to be taken up by the syncytiotrophoblast, where they can be stored, metabolised, oxidised or transported into fetal circulation (Barbour and Hernandez, 2018).
In this study, there was a positive correlation between maternal FBS in the first trimester of pregnancy and weight of the newborn. Diverse mechanisms might explain this situation. Maternal hyperglycemia leads to increased levels of circulating maternal and fetal insulin, itself a fetal growth hormone. Moreover, fetal hyperinsulinemia alters the expression of hypothalamic neurotransmitters, leading to increased weight of offspring. Insulin can also rewire the hypothalamic circuits regulating food intake in mice and thus could potentially affect body weight in the longer perspective (Kong et al, 2019). Dong et al (2013) reported that there was a positive relationship between maternal FBS concentrations and birth weight at 4-12 weeks of pregnancy, and it was also indicated that high maternal FBS was associated with greater weight and height at birth. However, in the study conducted by Salim et al (2004), the results showed that there was no significant difference in anthropometric indices between babies of mothers with gestational diabetes and those of non-diabetic mothers. This association was not confirmed in this study, probably due to the sampling from mothers who were under severe blood glucose control in that study.
In this study, there was a positive correlation between maternal BMI and the weight of newborn which is consistent with previous studies. In a systematic and meta-analytic study, Yu et al (2013) reported that the risk of macrosomia is increased in newborns whose mothers were overweight and obese before pregnancy. Zhao et al (2018) also showed that maternal overweight and obesity are correlated with an increased risk of macrosomia and LGA. In most studies, pre-pregnancy BMI played an important role in predicting birth weight. This may be related to insulin resistance. In addition to maternal insulin resistance in mothers with obesity that promotes modestly higher fasting glucose, maternal insulin resistance also affects adipose tissue by increasing maternal lipolysis, resulting in an excess of TG and free fatty acids in maternal circulation available to the fetal-placental unit (Barbour and Hernandez, 2018).
Metabolic syndrome and birth weight
In this study, linear regression test showed that MetS significantly affected birth weight. There are few studies on MetS during pregnancy and its effect on developing fetus and newborns, and almost all studies focus on individual components of MetS. In a study in Iran, mothers with MetS in mid-pregnancy had newborns with low birth weight, which is consistent with the present study (Sourinejad et al, 2019). However, in the study by Grieger et al (2018) MetS in early pregnancy was not associated with increased risk for LGA and SGA (Grieger et al, 2018). The reason for the difference in the results of this study is that there is no single definition for the MetS in pregnancy and different measurements have been carried out to diagnose metabolic syndrome.
Strengths and limitations
The strengths of the present study were its prospective nature and accurate and valid information on the MetS components. The non-randomised sampling was one of the limitations of this study, and since the sample size was relatively small, the generalisability of the results could be difficult. The most important limitation of the present study is the lack of a precise definition of MetS from valid sources. This study can be considered as one of the few studies defining the diagnostic criteria for pregnancy MetS, and in order to provide a more accurate definition for this common pregnancy problem in all societies, a broader sampling in different areas should be considered.
Conclusion
MetS and its components in the first trimester of pregnancy, including hypertriglyceridemia, obesity, high-blood pressure and high FBS, may act as significant predictors of birth weight. Birth weight have important implications for health across the life course and in future generations; infants with optimal and healthy birth weight have better infancy and adult health outcomes. Since unhealthy infant birth weight has serious and lasting consequences, attention should be paid to maternal MetS and its components to improve pregnancy and neonatal outcomes.
Key points
- Mothers with metabolic syndrome (MetS) in the first trimester of pregnancy had babies with lower birth weight
- Mothers with higher fasting blood sugar and body mass index gave birth to babies with higher weight
- MetS and its components should be monitored more closely, and managed accordingly in early pregnancy
CPD reflective questions
- Is maternal metabolic syndrome (MetS) in the first trimester of pregnancy related to the neonatal anthropometric parameters?
- Which component of maternal MetS in pregnancy is associated with fetal birth weight?
- Which component of maternal MetS in pregnancy is related to birth height?