Efecto de la obesidad durante el embarazo en el riesgo cardiometabólico de la madre y su efecto asociado en el crecimiento fetal

Abstract

Background and objective: Maternal obesity is associated with various complications that have adverse consequences for both the mother and the fetus. Despite being a very common condition, little has been studied about how maternal obesity could affect various indicators of cardiometabolic risk in uncomplicated pregnancies and how these could affect fetal growth. The evidence on this topic is even scarcer in the Latino American population in which the prevalence of obesity is known to be high and the risk of having cardiometabolic disorders is higher than in other populations. Considering the above, the general objective of this thesis was: to evaluate the association between obesity during pregnancy with the cardiometabolic risk of the mother and the associated effect on fetal growth. To respond to this objective, two studies were carried out: “Association of pregestational Body Mass Index and gestational weight gain with maternal indicators of cardiometabolic risk” and “Maternal cardiometabolic risk and fetal growth”. Study population and methodology. A prospective cohort study was carried out at the Hospital Materno Infantil Inguarán of SEDESA in Mexico City. Data from this cohort were used for the two studies performed. In the first study, mixed effects models were adjusted to describe the trajectories of maternal cardiometabolic risk indicators and to evaluate their association with maternal obesity. The second study used group-based trajectory models to identify groups of women who followed similar trajectories and group based multi-trajectory models to identify groups of women who followed similar trajectories of multiple indicators of cardiometabolic risk. Mixed-effects models were adjusted to assess the association between maternal cardiometabolic risk and fetal weight, and multiple linear regression models were performed to assess the association between maternal risk and birth weight. Results and conclusions. Study 1) Women with pregestational obesity and overweight had higher levels of cardiometabolic risk indicators at the beginning of pregnancy. Women with pre-gestational obesity had higher lipids concentrations in the beginning of pregnancy (TC: 𝛽̂=33.08, p=0.010; TG: 𝛽̂=31.29, p=<0.001) but the concentrations increased less than in women with normal pBMI (TC: 𝛽̂=-14.18, p=0.001; TG: 𝛽̂=-5.42, p<0.001). By the end of pregnancy, women with pre-gestational obesity had lower concentrations of lipids than women with normal pBMI. By contrast, women with pre-gestational obesity had higher glucose concentrations and higher blood pressure levels than women with normal pBMI over pregnancy. PgBMI appears to be more useful than monthly gestational weight gain in predicting biochemical and physiological changes during pregnancy, some of which (blood glucose and blood pressure) could increase cardiometabolic risk during current and medium and long-term pregnancy. Study 2) Two trajectory groups of maternal cardiometabolic risk indicators over pregnancy were identified, i.e. high and low levels across pregnancy. Compared with fetuses from women in low TG trajectory, fetuses of women in high TG trajectory were heavier (𝛽̂=48.24 g at 6th month) and those from this trajectory had higher increase of weight over pregnancy (𝛽̂=24.00 g). High TC trajectory was associated with higher fetal weight in the sixth month of pregnancy (𝛽̂=41.26 g) and fetuses from women in high glucose trajectory had lower gain weight as the pregnancy progressed (𝛽̂=-12.33 g) than fetuses from mothers in low trajectory. Fetuses from mothers with high systolic and diastolic blood pressure (SBP and DBP) trajectories had less weight in the sixth month of pregnancy (𝛽̂=-42.4g y 𝛽̂= -50.45 g). High TG trajectory was also associated with high birth weight (𝛽̂= 89.08 g), whereas high DBP trajectory was associated with lower birth weight (𝛽̂=-101.48 g). Furthermore, we proposed two cardiometabolic risk classification: 1) lipid profile and 2) cardiometabolic profile. Lipid profile had a positive association with fetal weight (𝛽̂=75.5 gr for transversal effect and 𝛽̂ =23.94 for the interaction with month) and birth weight ( 𝛽̂ =90.89 gr). Whereas, cardiometabolic profile was not associated with fetal growth. . Regarding fetal growth, it seems to be better to study the effect of each maternal cardiometabolic risk indicator individually. Since when we using the proposed risk classification, the joint effect of several indicators is considered and if they have different effects on fetal growth no effect can be observed. While to assess maternal cardiometabolic risk in the medium and long term, it would be more useful to use a classification that considers the set of risk indicators.

La obesidad en el embarazo se asocia con diversas complicaciones que tienen consecuencias adversas tanto para la madre como para el feto. A pesar de ser una condición muy común, se ha estudiado poco cómo la obesidad materna podría afectar diversos indicadores de riesgo cardiometabólico en embarazos que transcurren sin complicaciones y cómo estos podrían afectar el crecimiento fetal. La evidencia sobre este tema es aún más escasa en población latina en la que se conoce que la prevalencia de obesidad es elevada y el riesgo de tener alteraciones cardiometabólicas es mayor que en otras poblaciones. Tomando en cuenta lo anterior, el objetivo general de esta tesis fue: evaluar la asociación entre la obesidad durante el embarazo con el riesgo cardiometabólico de la madre y el efecto asociado en el crecimiento fetal. Para responder a este objetivo se realizaron dos estudios: “Asociación del IMCpg y la ganancia de peso gestacional con indicadores maternos de riesgo cardiometabólico” y “Riesgo cardiometabólico materno y crecimiento fetal”. Población de estudio y metodología. Se realizó un estudio de cohorte prospectivo en el Hospital Materno Infantil Inguarán de la SEDESA de la Ciudad de México. Los datos de esta cohorte se utilizaron para los dos estudios realizados. En el primer estudio se ajustaron modelos de efectos mixtos para describir las trayectorias de indicadores de riesgo cardiometabólico maternos y para evaluar su asociación con la obesidad materna. En el segundo estudio se utilizaron modelos de trayectorias grupales para identificar grupos de mujeres que seguían trayectorias similares y modelos de multi-trayectorias grupales para identificar grupos de mujeres que seguían trayectorias similares de múltiples indicadores de riesgo cardiometabólico. Para evaluar la asociación con el crecimiento fetal se ajustaron modelos de efectos mixtos para el caso del peso fetal y modelos de regresión lineal múltiple para el peso al nacer. Resultados y conclusiones. Estudio 1) Las mujeres con sobrepeso u obesidad pregestacionales tuvieron niveles más elevados de indicadores de riesgo cardiometabólicos al inicio del embarazo. Mujeres con obesidad pregestacional tuvieron concentraciones más elevadas de colesterol total (CT) y triacilgliceróles (TG) al inicio del embarazo (TC: