Maternal plasma transforming growth factor-β1 (TGF-β1) and newborn size: the Araraquara Cohort Study

Abstract Objective To investigate associations of maternal and cord blood cytokine patterns with newborn size and body composition. Methods This cross-sectional study involved 70 pregnant women and their healthy newborns selected from the "Araraquara Cohort Study". Newborn anthropometric measurements were recorded at birth. Body composition was evaluated by air displacement plethysmography. Maternal blood samples were collected from pregnant women between 30 and 36 weeks of gestation, and umbilical cord blood samples were collected immediately after placenta discharge. The concentrations of the cytokines were determined in plasma by ELISA. Multiple linear regression models were used to assess associations between maternal and cord blood cytokine concentrations and newborn anthropometry and body composition measurements. Results Maternal plasma TGF-β1 concentration was inversely associated with newborn weight (β= -43.0; p= 0.012), length (β= -0.16, p= 0.028), head circumference (β= -0.13, p= 0.004), ponderal index (β= -0.32, p= 0.011) and fat-free mass (β= -0.05, p= 0.005). However, the association persisted just for head circumference (β= -0.26; p= 0.030) and ponderal index (β= - 0.28; p= 0.028), after adjusting for pre-gestational BMI, gestational weight gain, gestational age, hours after delivery, newborn sex, smoking and alcohol consumption. Conclusions Maternal plasma TGF-β1 concentration may be involved in the regulation of newborn size, mainly head circumference and ponderal index. Further cohort studies are necessary to investigate the role of TGF-β1 in different trimesters of pregnancy and its effect during the early stages of fetal development.

Relação entre ganho de peso gestacional e composição corporal do concepto / The relationship between gestational weight gain and body composition of the fetus

Introdução: O aumento da adiposidade no ambiente intrauterino e alterações na composição corporal neonatal podem estar relacionados com obesidade e doenças crônicas no futuro. O ganho de peso gestacional (GPG) está associado à obesidade infantil, porém, estudos que avaliaram a relação entre o GPG materno e a composição corporal do concepto revelaram resultados inconsistentes, especialmente no que se refere à adiposidade fetal. Objetivo: Avaliar a relação entre o GPG materno e a adiposidade do feto e composição corporal neonatal. Métodos: Estudo epidemiológico prospectivo do tipo coorte, realizado em Araraquara e região, envolvendo gestantes atendidas em 34 Unidades de Saúde do SUS e na Maternidade Municipal "Gota de Leite". As gestantes foram acompanhadas em três períodos gestacionais (≤19, 20-29 e 30-39 semanas), durante o parto, e posteriormente até 72 horas após o parto. Foram avaliadas 1005 gestantes no 1º período gestacional, 1002 pares de gestantes e fetos no 2º período, 991 pares de gestantes e fetos no 3º período e 412 pares de mães e respectivos neonatos. A taxa de ganho de peso (TGP) foi calculada a partir da diferença entre o peso aferido no período gestacional específico menos o peso avaliado no período gestacional anterior, dividido pelo número de semanas correspondente a esse intervalo. O GPG total foi obtido pela diferença entre o peso aferido na data do parto e o peso pré-gestacional e classificado em insuficiente, adequado e excessivo, de acordo com a última diretriz do Institute of Medicine (IOM). A adiposidade fetal e a composição corporal do neonato foram avaliadas, respectivamente, por ultrassonografia e pletismografia por deslocamento de ar. Modelos de regressão linear múltipla foram construídos de acordo com um conjunto de ajustes mínimos suficientes sugeridos por gráficos acíclicos direcionados, considerando os seguintes fatores de confusão: idade, cor da pele/etnia, escolaridade, renda per capita, tabagismo, ingestão de alcool, paridade, diabetes mellitus, hipertensão arterial, altura, IMC pré-gestacional, sexo, idade gestacional ao nascer, horas de vida do neonato. O nível de significância em todos os testes foi α = 5%. Resultados: Durante o 2º período gestacional, verificou-se que para cada 0,1 kg/semana da TGP, houve um aumento de 0,222 mm (p=0,012), 0,462 cm2 (p <0,001), e 0,310 cm2 (p <0,001) no tecido adiposo subcutâneo do abdômen, coxa e braço do feto, respectivamente. Também houve associação entre a TGP materna no 3º período gestacional e deposição de gordura subcutânea no braço (ß=0,484 cm2; p=0,001) e na coxa (ß=0,480 cm2; p=0,049) do feto. Quanto à composição corporal neonatal, observou-se que para cada 1 kg do GPG total houve aumento de 0,004 Kg (p=0,002) na massa gorda, 0,084% (p=0,025) no percentual de massa gorda e 0,009 Kg (p <0,001) na massa livre de gordura do neonato. Crianças de mulheres com GPG total insuficiente apresentaram massa livre de gordura 0,104 kg (p=0,009) menor que os neonatos de mães com GPG total adequado. Conclusão: De acordo com nosso conhecimento, este é o primeiro estudo na literatura internacional que investigou a associação entre ganho de peso materno e adiposidade fetal e composição corporal neonatal. Os resultados mostram um impacto diferente da TGP materno sobre o acúmulo de gordura fetal, de acordo com o período gestacional investigado. Também houve associação positiva entre GPG total e massa gorda, percentual de massa gorda e massa livre de gordura do neonato. Mães com GPG total insuficiente tiveram neonatos com menor massa livre de gordura.

Introduction: The increase in adiposity in the intrauterine environment and changes in neonatal body composition may be related to obesity and chronic diseases in the future. Gestational weight gain (GWG) is associated with childhood obesity, however, studies that evaluated the relationship between the maternal GWG and the body composition of the fetus revealed inconsistent results, especially with regard to fetal adiposity. Objective: To evaluate the relationship between maternal GWG and adiposity of the fetus and body composition of the newborn. Methods: This is an epidemiological prospective cohort study, carried out in Araraquara and region, involving pregnant women attended at 34 Health Units from the Brazilian National Health Service - SUS and at the Municipal Maternity "Gota de Leite". The pregnant women were followed up in the respective gestational periods: ≤ 19, 20-29 and 30-39 weeks, during delivery, and later up to 72 hours after delivery. One thousand and five (1005) pregnant women were evaluated in the 1st period of pregnancy, 1002 pairs of pregnant women and fetuses in the 2nd period, 991 pairs of pregnant women and fetuses in the 3rd period, and 412 pairs of mothers and newborns. The rate of weight gain (RWG) was calculated based on the difference between the weight measured in the gestational period minus the weight assessed in the previous gestational period, divided by the number of weeks corresponding to that interval. GWG was obtained by the difference between the weight measured at the date of delivery and the pre-gestational weight, and classified as insufficient, adequate, and excessive, according to the last guidelines of the Institute of Medicine (IOM). The fetal adiposity and body composition of the newborn were evaluated, respectively, by ultrasound and plethysmography by air displacement. Multiple linear regression models were constructed considering a set of sufficient minimum adjustments suggested by directed acyclic graphs, considering the following confounders: age, skin color/ethnicity, schooling, per capita income, smoking, alcohol intake, parity, diabetes mellitus, arterial hypertension, height, pre-gestational BMI, sex, gestational age at birth, hours of life of the newborn. The level of significance in all tests was α = 5%. Results: During the 2nd gestational period, it was found that for each 0.1 kg/week of RWG, there was an increase of 0.222 mm (p = 0.012), 0.462 cm2 (p<0.001), and 0.310 cm2 (p<0.001) in subcutaneous adipose tissue in the abdomen, thight and arm of the fetus, respectively. There was also an association between the RWG in the 3rd gestational period and deposition of subcutaneous fat in the arm (ß=0.484 cm2; p=0.001) and thigh (ß=0.480 cm2; p=0.049) of the fetus. Concerning the newborn's body composition, it was observed that for each 1 kg of total GWG there was an increase of 0.004 Kg (p=0.002) in the fat mass, 0,084% (p=0.025) in the percentage of fat mass, and 0.009 Kg (p<0.001) in the fat-free mass of the newborn. Considering the guidelines of the IOM, neonates of mothers who had an insufficient total GWG had a fat-free mass of 0.104 kg (p=0.009) less than those born to women with adequate total GWG. Conclusion: As far as we know, this is the first study in the international literature that investigated the association between maternal weight gain in three different periods of gestation and fetal adiposity and newborn adiposity. The results show a different impact of the maternal RWG on the accumulation of fetal fat, according to the gestational period investigated. There was also a positive association between total GWG and mass fat, percentage of fat mass, and fat-free mass of the fetus, regardless of pre-gestational BMI. Women with insufficient total GWG had neonates with lower fat-free mass.