Environmental factor that acts in the early life may influence the risk of diseases in adult life [
A series of worldwide epidemiological studies extended the initial observations on the association between pre- and postnatal growth and cardiovascular disease, in order to include relations between initial growth patterns and increased risk for hypertension, impaired glucose tolerance, type 2 diabetes, insulin resistance, and obesity in adult life [
Given the increasing prevalence of obesity in the world, a variant of the Barker hypothesis was created, in which excessive nutrition during pregnancy and high birth weight may be related to chronic disease in adult life, such as obesity and correlated conditions in adulthood [
Just as intrauterine growth restriction (IURG) forces the fetus to restructure the metabolic machinery, exposure to excessive maternal nutrition (secondary to the current epidemic of diabetes and obesity) may be associated with parallel increase of macrosomic births. Recent studies show strong associations between neonatal adiposity and metabolic disorders in adulthood [
Therefore, this paper aims to study the relation between birth weight, growth in the first year of life, and risk factors for cardiovascular disease and subclinical atherosclerosis in adults of the “Professor Samuel B. Pessoa” Health Center-School (CSE) of the Faculty of Medicine from the University of São Paulo.
The study had an analytical and observational circumscription. It was conducted in adults who had medical records in the CSE as newborns or infants from the period between 1977 and 1989 and who are still being followed in the Health Center-School nowadays. All subjects agreed to participate in the study and gave the Term of Free and Informed Consent Form (ICF) in writing, according to the Resolution from 1996 of the Brazilian National Health Council.
The research project was developed at the Health Center-School (CSE) from the Medical School of the University of São Paulo, where practices of primary health care are developed with adults selected from the existing medical records. Other health centers apart from the CSE collaborated for this study: Children’s Institute from the “Hospital das Clínicas” of the University of São Paulo (ICr-HCFMUSP) and “Hospital Universitário” of the same university (HU-USP). The following inclusion criteria for participation in the study were considered: subjects must currently have been between 20 and 31 years old, which means, being born between 1977 and 1989 for both sexes; subjects must have read and signed the Term of Free and Informed Consent Form (ICF); their birth weight and perinatal data must have been recorded in their medical records; the subjects should have been followed at the CSE when they were at the pediatric age group; and they should also be currently subjected to regular medical monitoring in the CSE.
In order to form the groups of study, we reviewed 738 medical records, of which 645 had neonatal data required in the inclusion criteria. Of these ones, 298 users answered our call and signed the Term of Free and Informed Consent Form. Once the study included the evaluation of atherosclerosis by ultrasound and by graphical methods, and considering that the frequency of cardiovascular disease mortality is 31.3% in our midst [
Flowchart of the study’s group constitution considering the participants’ birth weight.
The weight gain in the first year of life was obtained in the medical records of 50 subjects among the 88 participants. These medical records were divided in two groups (see Figure
Flowchart of the constitution of the study groups based on weight gain in first year of life, according to gender.
The 88 subjects were divided into groups according to two criteria: birth weight and weight gain in the first year of life. We used two values as references to form the groups: 2,500 grams and 3,500 grams. A birth weight below 2,500 grams is considered as low birth weight [ Birth weight: Weight gain in the first year of life:
The selected subjects had their data collected through a structured questionnaire which addressed sociodemographic characteristics (age, gender, ethnicity, educational level, and per capita income), presence of cardiovascular risk factors (smoking, alcohol consumption, and drug use), previous diagnoses (arterial hypertension, diabetes mellitus, dyslipidemia, and cardiovascular disease), conditions of birth (weight, gestation period), weight and height development in early life, and diseases in the neonatal period and childhood.
Anthropometric parameters were measured using techniques and equipment in accordance with the recommendations of the World Health Organization (WHO) and the
Participants were considered diabetic when they had had a previous history of diabetes mellitus diagnosis, when they had used medications for diabetes treatment, or when their fasting glucose level was greater than or equal to 126 mg/dL [
The established criteria for metabolic syndrome diagnosis consist in the presence of three or more of the following items [
Fat layers of the abdominal wall thickness (minimum, maximum, and peritoneal) and visceral fat (liver) were measured by ultrasound. The ultrasound images were obtained with
The standardizing of the ultrasound method for measurement of the thickness of the carotid intima-media followed the protocol of the Center for Clinical and Epidemiological Research of HU-USP. The bifurcation of the carotid arteries was analyzed in a length of 3 centimeters (cm) in search for plates. The image of the common carotid over 1 cm was analyzed as well, beginning 1 cm below the bifurcation of the common carotid. The intima-media thickness (IMT) was measured in all participants in a standardized way with equipment
The carotid-femoral pulse wave velocity (PWV) was measured with a validated automatic device (
This examination was conducted using 12 derivations with records of the heart’s electrical activity captured by electrodes placed on arms and legs of the subject. After the record, pace, cardiac frequency, and electrocardiogram (ECG) traces tests were made in the Laboratory of Electrocardiography of the Heart Institute (Instituto do Coração (INCOR)/HC-FMUSP).
The database was created using the
The analysis of the sociodemographic characteristics of the study group showed that it had a similar frequency of white and black people. The average age was 25.5 years, with a predominance of female subjects. Over half of the subjects (62.5%) reported that they had completed high school. 64.8% had an income per capita higher than 1 minimum wage. Smoking, alcohol consumption, and drug abuse were mentioned, respectively, by 23.9%, 10.2%, and 5.7% of the participants. Previous personal history of hypertension, dyslipidemia, and mental illness were mentioned, respectively, by 6.8%, 2.3%, and 8% of the subjects. These data are displayed in Table
Sociodemographic aspects and previous conditions of the subjects.
Characterization | |
---|---|
Age (years) | 25.5 years (2.9) |
Gender | |
Female | 52 (59.1%) |
Ethnicity | |
Afro-descendant | 43 (48.9%) |
Education (years) | |
Has finished High school | 55 (62.5%) |
Per capita income | |
|
57 (64.8%) |
Habits | |
Smoking | 21 (23.9%) |
Alcohol consumption | 9 (10.2%) |
Drug use | 5 (5.7%) |
Previous medical conditions | |
Arterial hypertension | 6 (6.8%) |
Diabetes mellitus | 0 (0.0) |
Dyslipidemia | 2 (2.3%) |
Cardiovascular disease | 0 (0.0) |
Mental disorder | 7 (8.0%) |
The anthropometric profile showed that the average body mass index (BMI) of the entire group was 24.6 kg/m2. A BMI > 25.0 kg/ m2 was found in 37.5% of the group while obesity (BMI > 30.0 kg/m2) in 10.2% of the participants. Increased waist circumference (WC) and increased waist-hip ratio (WHR) were detected in 29.5% and 46.6% of adults, respectively. The study of the blood pressure levels showed that 12.5% of the adults could be diagnosed with hypertension.
The anthropometric profile and blood pressure measurements in relation to birth weight are described in Table
Birth weight and subclinical atherosclerosis.
Regression coefficient (RC)/confidence interval (95%) | |||
---|---|---|---|
Low weight |
Increased weight |
Reference weight | |
|
|
|
|
|
|||
1BMI (Kg/m2) | −1.518 |
2.832** |
20.811 |
1BMI > 25.0 Kg/m2 | −0.065 |
0.317** |
−0.179 |
Increased WC2 (%) | −0.046 |
0.284** |
0.715 |
Increased WHR3 (%) | −0.323** |
0.280** |
0.495 |
4DBP (mm Hg) | −4.744** |
0.719 |
63.885 |
Glucose level (mg/dL) | −0.400 |
3.808** |
76.058 |
HDL cholesterol < 40 mg/dL (%) | −0.272** |
0.024 |
0.203 |
|
|||
|
|
|
|
|
|||
5Minimum SAT (mean and standard deviation) | −1.614 |
4.354** |
8.112 |
Maximum SAT (mean and standard deviation) | −2.486 |
7.095** |
11.367 |
|
|||
|
|
|
|
|
|||
Right lobe (mean and standard deviation) | −3.863 |
6.896*** |
82.206 |
Right lobe > 75th percentile | −0.124 |
0.361*** |
−0.366 |
|
|||
|
|
|
|
|
|||
Mean IMT6 > 75th percentile | −0.242** |
−0.039 |
0.371 |
2WC: Waist circumference.
3WHR: Waist-rip ratio.
4DBP: Diastolic blood pressure.
5SAT: Subcutaneous adipose tissue.
6IMT: Intima-media thickness.
7BW: Birth weight.
Low birth weight (<2,500 grams) was inversely correlated with increased waist-to-hip ratio according to the regression coefficient (RC) −0.323, confidence interval (CI) 95% [−0.571, −0.075]
No participant had diabetes mellitus. The mean blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides among the study participants were, respectively, 81.7 (±6.5), 160.1 (±35.6), 90.0 (±23.9), 47.7 (±13.1), and 93 mg/dL (±78.1). Dyslipidemia was diagnosed in 29.5% of the subjects. Metabolic syndrome was found in 8.0% of them.
Low birth weight was inversely correlated with low HDL-cholesterol values, according to RC = −0.272, CI 95% [−0.516, −0.029], with
The mean measurements of minimum, maximum, peritoneal, and visceral (of right lobe of the liver) subcutaneous abdominal fat (SAT) were, respectively, 11.3 (±7.1), 21.4 (±12.7), 13.2 (±5), and 96.0 (±11) mm. The frequencies of minimum, maximum, and peritoneal SAT above the 75th percentile were 24.7%, 24.7%, and 24.1%, respectively. Analysis of the visceral fat showed that 24.1% of the participants had right liver lobe above the 75th percentile and that 18.4% of the adults had abnormal liver echogenicity.
Birth weight greater than 3,500 grams was positively associated with mean values of minimal subcutaneous abdominal fat (SAT) (RC = 4.354, 95% CI [0.821, 7.888]
The mean of the left carotid’s average and maximum IMT were 0.47 (±0.08) and 0.58 (±0.10) mm, respectively. The frequencies of the left carotid’s average and maximum IMT above the 75th percentile were 24.1% for both measures. The mean of the right carotid’s average and maximum IMT were 0.46 (±0.07) and 0.57 (±0.09) mm, respectively. The frequencies of the right carotid’s average and maximum IMT above the 75th percentile were 23% and 21.8%, respectively. The mean of the mean IMT (LC + RC)/2 was 0.47 (±0.06) mm. The frequency of mean IMT (LC + RC)/2 above the 75th percentile was 18.4%.
Low birth weight was inversely correlated with left carotid’s average IMT above the 75th percentile (RC = −0.242, CI 95% [−0.476, −0.008],
The study of arterial elasticity showed average pulse wave velocity (PWV) equal to 7.91 (±1.12) meters/second, with 24.7% of the study’s participants with PWV values above the 75th percentile. Low birth weight and birth weight greater than 3,500 g were not correlated with arterial stiffness through the pulse wave velocity exam.
Changes in the electrocardiogram (that can be correlated with atherosclerosis, such as ventricular preexcitation, atrioventricular block, atrial ectopic rhythm, left atrial enlargement, early repolarization, and ventricular hypertrophy) were detected in 14.8% of adults that participated in our study, but they were not associated with low birth weight, nor with increased birth weight (>3,500 g).
Information about weight gain in the first year of life of the study participants was obtained from 50 of the 88 adults. Weight gain in the first year of life was considered insufficient when lower than 6,300 grams for males and lower than 5,700 grams for females. Weight gain in the first year of life was considered adequate when equal to or higher than 6,300 grams for males and equal to or higher than 5,700 for females.
The insufficient weight gain in the first year of life was not correlated with anthropometric parameters, blood pressure measurements, metabolic profile, measurement of abdominal fat, or visceral fat measurement. The study of the relation between measurement of intima-media thickness (IMT) of the carotid arteries and weight gain in the first year of life is summarized in Table
Weight gain in the first year of life and atherosclerosis.
Regression coefficient (RC)/confidence interval (95%) | ||
---|---|---|
Insufficient weight gain in the first year of life | Reference: adequate weight gain in the first year of life | |
|
||
Left carotid |
|
|
Average IMT1 (mean and standard deviation) | −0.046** |
−0.357 |
Average IMT1 above the 75th percentile | −0.253** |
0.421 |
Average IMT1 (LC + RC)/2 |
|
|
Average IMT1 (LC2 + RC3)/2 | −0.038** |
0.375 |
Average IMT1 (LC + RC)/2 >75th percentile | −0.241** |
−0.147 |
2Left carotid.
3Right carotid.
Insufficient weight gain in the first year of life was negatively correlated with left carotid’s average IMT values (CR = −0.046, 95% CI [−0.086, −0.006]
The study of the relation between the anthropometric profile of the participants and their birth weight showed that only birth weight greater than 3,500 grams was positively associated with body mass index (BMI) and the frequency of overweight, in accordance with what literature discusses about developmental origins of obesity [
In this study, low birth weight was inversely associated with increased WHR (wait-hip ratio). Yajnik et al. observed that individuals born with lower weights showed a higher proportion of body fat in adult life when compared to those who were born heavier [
Birth weight greater than 3,500 grams was also correlated to increased abdominal fat and increased waist-rip ratio (WHR), with literature showing that individuals born heavier might also weigh more in adult life, but with an adequate corporal hormonal composition and with an adequate body fat distribution [
Regarding blood pressure, low birth weight was inversely related to levels of diastolic arterial blood pressure, with medical literature showing the relation between fetal growth restriction and arterial hypertension [
The study of the metabolic profile of the subjects showed that low birth weight was inversely correlated with reduced HDL-cholesterol frequency. The first studies on fetal origins of dyslipidemia showed that low birth weight was associated with atherogenic lipid profile in adult life [
Birth weight greater than 3,500 grams was positively associated with average fasting glucose levels. Population studies showed many possibilities, both with those with low birth weight and with those with higher birth weight linked with glycemic alterations, with studies describing a U-shaped curve [
Nonalcoholic fatty liver disease (NAFLD) has been associated with metabolic disorders and subclinical atherosclerosis, often accompanied by abnormal liver function [
The evaluation of subcutaneous and hepatic fat by ultrasonography of this study’s subjects showed that birth weight higher than 3,500 grams was associated with more presence of both subcutaneous abdominal fat and visceral fat. Subcutaneous fat seems to be more strongly related to total body fat [
Increased intima-media thickness (IMT) of the carotid arteries is considered an important marker for cardiovascular disease [
The mechanisms that explain the low birth weight, insufficient or excessive weight gain in the first year of life, and risk factors for cardiovascular disease in adulthood take into account the theory of Thrifty Phenotype [
Despite the fact that the medical literature associated low birth weight with greater vascular rigidity through pulse wave velocity [
The present study confirms the hypothesis of the association between birth weight and risk for atherosclerotic vascular disease. This paper highlights that birth weight over 3,500 grams and low birth weight are two different phenotypic expressions, but they are both related to increased risk for cardiovascular disease and subclinical atherosclerosis. It also shows that insufficient weight gain in the first year of life is also associated with a greater risk for subclinical atherosclerosis disease.
The authors declare that there is no conflict of interests regarding the publication of this paper.
Maria Helena Valente, Filumena Maria da Silva Gomes, Ana Maria de Ulhôa Escobar, and Sandra J. F. E. Grisi have designed and conceived the experiment. Maria Helena Valente, Filumena Maria da Silva Gomes, and Isabella Judith Martins Benseñor collected data and structured the research. Maria Helena Valente, Filumena Maria da Silva Gomes, Isabella Judith Martins Benseñor, Alexandra Valéria Maria Brentani, and Sandra J. F. E. Grisi have analysed the data. Maria Helena Valente and Filumena Maria da Silva Gomes have written the paper and reviewed the data.