We conducted this study to investigate whether fetal growth restriction is associated with changes in cardiovascular risk factors among urban individuals aged 10-20 years.

This retrospective cohort study was conducted among a predominantly urban population in the Brazilian northeast. The Research Ethics Committee of the Assis Chateaubriand Maternity Teaching Hospital – Federal University of Ceará approved this study, by means of the protocol 197.298. The study was conducted between February and August 2013 and respected all ethical and legal guidelines for research on humans.　An informed consent form was obtained from all participants or their legal guardians.

The eligibility criteria were the absence of genetic syndromes, cardiovascular and/or endocrine diseases and to be healthy.　Healthy subjects were understood to be participants without any medical conditions that act directly or indirectly to increase the cardiovascular risk. Large for gestational age newborns were excluded.

From the data recorded in the books of births, patients with a low birth weight (<2,500 g) and normal weight (between 2,500 and 3,999 g) were identified, to search for their records and analyze the neonatal data. The invitation to participate in this study was made through personal visits, phone calls and letters, using the contact data from the medical records.　During the first conversation with the adult responsible for the adolescent, the study objectives were explained and a day was scheduled for the anthropometric and laboratory evaluations to be carried out.

Statistical analyses: The sample size was calculated considering an alpha error of 5% and a confidence level of 80% (beta error of 20%) and, based on the occurrence of previous studies with relative risk for complications in the long term of approximately 2.3, an "n" of 160 patients was found.　 The Shapiro-Wilk test was used to test the normality of the continuous variables.　The Student t-test, Kruskall Wallis test and Mann-Whitney test were used according to the normality of the continuous variables and Chi-square test for categorical variables.　The level of significance was set at P<0.05.　The Stata program version 12.0 was used for the statistical analysis.

Web Table I shows the baseline data of the mothers of the participants, demonstrating no differences between the groups. Table I compares the perinatal data between the two groups. Neonatal outcomes were less favorable in the group with FGR: prematurity in more than 50% (P=0.01), 80% with a birth weight less than 2,500 g (P<0.001), and shorter height and smaller head and thoracic circumference (P<0.001).　

TABLE  I  Perinatal Data  in the Study Population

Clinical and anthropometric data of the adolescents was similar in the two groups except for higher hip-circumference and higher total cholesterol levels in those without FGR (P=0.04 for both) (Table II). No differences were noted between the groups with regards to the brachial artery measurements (Table III).

TABLE II	Clinical and Metabolic Data in Adolescents According to Fetal Growth Restriction 

TABLE IIII Brachial Artery Measurements in Adolescents According to Birthweight

The results only revealed a few anthropometric, metabolic, and endothelial differences associated with fetal growth restriction, specifically, hip circumference and total cholesterol, both with lower values in FGR (P=0.04 for both). In general, those exposed to FGR seem to be thinner and shorter, which affects other measurements such as waist and abdominal circumference, as well as the percentage of total fat, but without statistical differences.

This study has some limitations.　The records of neonatal and maternal data were obtained at delivery for purposes of care and not to conduct research, leading to a lack of annotation of some parameters.　In addition, possible errors filling in the registration can no longer be confirmed or corrected, due to the time elapsed.　 As no previous measurements of the parameters analyzed in this study had been performed, it was not possible either to identify whether there had been rapid growth during childhood or to verify if it would have a more significant effect than FGR, as found in some studies.　Nor was it possible to carry out the analysis excluding premature subjects in both groups, as this would cause the loss of more than half the patients in the group with FGR.　In addition, prior to 1998, many records were destroyed due to inadequate care, so the number of participants over 15 years old was reduced. To reduce bias, we controlled for the socioeconomic status. Furthermore, we have not investigated the effects of rapid growth in children with FGR. An important feature in this study is that socioeconomic status and the same day of birth was accounted for and the groups were similar in maternal and family characteristics, mean chronological age and gender. Medical registers were used to investigate weight and height at birth in order to minimize wrong values. We used international parameters to facilitate future comparisons with our data.

Monteiro,　et al. [9], in a cohort study in Southern Brazil, with adolescents aged 14 to 16 years found no association between FGR and overweight/obesity among girls, whereas for boys, the association was positive for both conditions.　 Another study, which gathered data from five countries: India, Guatemala, the Philippines and Brazil showed that the greatest above normal weight gain at any age was related to elevated blood pressure in young adults, who had their weight monitored after birth, at 12, 24 and at 48 months, with the latest measurements taken on average at age 23.　However, faster weight gain in infancy did not represent a greater risk than weight gain at other ages [30].　Some authors argue that it is not fetal restriction or low birth weight that impact negatively on cardiovascular health, but instead greater than expected growth, either in weight or height, also known as　catch-up growth. Furthermore, the effect of accelerated growth itself after birth is controversial.　In lower income countries, its occurrence appears to reduce the morbidity and mortality of children with FGR [28]; a fact not observed in countries with high incomes, where it appears to be associated with an increased prevalence of cardiovascular disease [21]. It is possible that other measurements besides birth weight may be more strongly associated with adverse cardiovascular outcomes than birth weight alone [28].

These results do not exclude the possibility of an association between accelerated growth during the first years of life in those with FGR and worsening risk factors.　It is suggested that prospective longitudinal studies with multiple assessments throughout the study period are performed to verify the effect of accelerated growth in similar populations.

Contributors: All authors have planned, executed, construction of the research, implemented of survey, analysis and interpretation of data and approved the final version of the manuscript.

Funding: Financing through scholarships from the following institutions: Ceará Foundation for Scientific and Technological Development (Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico) (FUNCAP) and the Coordination of Personnel Improvement in Higher Education (Coordenação de Aperfeiçoamento de Pessoal do Nível Superior) (CAPES).

Competing interests: None stated.