In a recent American Journal of Obstetrics and Gynecology study, researchers explore the association between maternal insulin resistance during the early, middle, and late stages of an uncomplicated pregnancy with fetal fat deposition to understand the influence of maternal glucose regulation during gestation on child adiposity.
Study: Maternal insulin resistance in pregnancy is associated with fetal fat deposition: findings from a longitudinal study. Image Credit: vovidzha / Shutterstock.com
Background
A growing body of research indicates that prenatal accrual adipose tissue in the fetus impacts childhood and adult obesity, which is a serious health concern.
During fetal development, adipogenesis occurs mainly during the middle and late gestation periods. This process is influenced by the maternal nutritional environment, especially glucose and insulin concentrations.
Several studies have reported associations between newborn adiposity and maternal conditions during pregnancy, such as maternal body mass index (BMI) and gestation weight gain. However, while the relationship between fetal fat deposition and maternal glucose sensitivity has been established, the influence of maternal insulin resistance and its gestational timing on fetal fat deposition remains unclear.
About the study
In the present study, researchers performed a longitudinal study of 137 normal pregnancies. They used fetal ultrasonography images and fasting maternal blood samples to investigate the longitudinal and cross-sectional associations between maternal insulin resistance and fetal adiposity.
Participants were excluded if they had uterine anomalies, hypertension, diabetes, other pre-existing comorbidities, renal, endocrine, or hepatic disorders, chromosomal abnormalities, congenital disorders, a history of smoking or drug use, or were receiving systemic corticosteroids.
Insulin resistance during gestation was measured using the homeostasis model assessment of insulin resistance (HOMA-IR). Maternal venous blood was collected at 12, 20, and 30 weeks of pregnancy to measure fasting insulin concentrations and plasma glucose levels. The periods were decided based on evidence of changing endocrine parameters during gestation.
Two-dimensional (2D) fetal ultrasonography was performed within four days of maternal blood sample collection to obtain head circumference, abdominal circumference, femur length, and biparietal diameter measurements, all of which were used to estimate fetal weight.
Three-dimensional (3D) ultrasonography was then used to measure fat mass at the mid-upper arm, abdomen, and mid-thigh at 20 and 30 weeks, but not at 12 weeks, as histologically evident fetal fat deposition only occurs after 14 to 16 weeks.
Self-reported pre-pregnancy weight and height measured during the first prenatal hospital visit were used to calculate maternal BMI. Medical records during the pregnancy were used to calculate gestational weight gain, which was then characterized as adequate, inadequate, or excessive. The data were then analyzed to estimate fetal adiposity, with statistical analyses used to identify correlations between maternal glucose sensitivity and fetal fat deposition.
Study findings
Maternal HOMA-IR levels during mid and late gestation positively correlate with estimated fetal adiposity but not with estimated fetal weight. In addition, the HOMA-IR values were significantly associated with race and ethnicity, with Hispanic mothers having higher HOMA-IR values than non-Hispanic mothers.
The correlation between fetal adiposity and maternal HOMA-IR at 20 and 30 weeks of gestation remained significant, even after adjusting for maternal BMI, race, and ethnicity. The correlation also did not significantly change after excluding mothers with gestational diabetes mellitus.
Future directions for maternal care
Taken together, maternal insulin levels during mid-gestation could serve as an essential biomarker to detect the risk of fetal adiposity, thereby providing time for clinical interventions before maximum fetal fat deposition occurs. Since fat deposition in the fetus can be histologically observed only between 14-16 weeks, the short window between then and 20 weeks could be critically important in detecting maternal insulin resistance and evaluating the risks of fetal adiposity and future childhood adiposity.
Mothers with gestational diabetes mellitus detected before 24-28 weeks are at a higher risk of complicated pregnancies than mothers diagnosed during the third trimester. Similar early screening of maternal glucose sensitivity could help predict obesity risks for the child.
One of the proposed mechanisms to explain the correlation between maternal insulin resistance and fetal adiposity included the increased trans-placental transport of glucose to the fetus, which would elevate the pancreatic beta cell function and increase fetal insulin levels. Higher fetal insulin levels increase glucose uptake, thus stimulating the liver to store excess glucose as triglycerides and glycogen.
Conclusions
The current study explored the association between maternal insulin resistance at different stages of gestation and fetal adiposity. The results suggested a strong correlation between maternal glucose sensitivity and fetal fat deposition during the middle and late-gestation periods, which remained significant after accounting for gestational diabetes mellitus, maternal BMI, race, and ethnicity.
Mid-gestation maternal insulin resistance can be an important biomarker to assess fetal, newborn, and childhood obesity risks.
Journal reference:
- Ikenoue, S., Waffarn, F., Sumiyoshi, K., et al. (2022). Maternal insulin resistance in pregnancy is associated with fetal fat deposition: findings from a longitudinal study. American Journal of Obstetrics and Gynecology. doi:10.1016/j.ajog.2022.10.015