Relationships between intrauterine fetal growth trajectories and markers of adiposity and inflammation in young adults

Abstract

Background: There is now good evidence that events during gestation significantly influence the developmental well-being of an individual in later life. This study aimed to investigate the relationships between intrauterine growth trajectories determined by serial ultrasound and subsequent markers of adiposity and inflammation in the 27-year-old adult offspring from the Raine Study, an Australian longitudinal pregnancy cohort.

Methods: Ultrasound fetal biometric measurements including abdominal circumference (AC), femur length (FL), and head circumference (HC) from 1333 mother-fetal pairs (Gen1-Gen2) in the Raine Study were used to develop fetal growth trajectories using group-based trajectory modeling. Linear mixed modeling investigated the relationship between adult body mass index (BMI), waist circumference (WC), and high-sensitivity C-reactive protein (hs-CRP) of Gen2 at 20 (n = 485), 22 (n = 421) and 27 (n = 437) years and the fetal growth trajectory groups, adjusting for age, sex, adult lifestyle factors, and maternal factors during pregnancy.

Results: Seven AC, five FL and five HC growth trajectory groups were identified. Compared to the average-stable (reference) group, a lower adult BMI was observed in two falling AC trajectories: (β = -1.45 kg/m², 95% CI: -2.43 to -0.46, P = 0.004) and (β = -1.01 kg/m², 95% CI: -1.96 to -0.05, P = 0.038). Conversely, higher adult BMI (2.58 kg/m², 95% CI: 0.98 to 4.18, P = 0.002) and hs-CRP (37%, 95% CI: 9-73%, P = 0.008) were observed in a rising FL trajectory compared to the reference group. A high-stable HC trajectory associated with 20% lower adult hs-CRP (95% CI: 5-33%, P = 0.011).

Conclusion: This study highlights the importance of understanding causes of the unique patterns of intrauterine growth. Different fetal growth trajectories from early pregnancy associate with subsequent adult adiposity and inflammation, which predispose to the risk of diabetes and cardiometabolic disease.

Fig. 1. Flow diagram of Raine Study participants attending the 20, 22 and 27-year follow-up.

Flow diagram of Raine Study participants attending the 20, 22 and 27-year follow-up with completeadult body mass index (BMI), waist circumference (WC) and lifestyle data.

Fig. 2. Fetal growth trajectories using abdominal circumference (AC), femur length (FL), and head circumference (HC) anthropometric markers.

Reproduced from Yadav et al. [30]. DOI:10.1097/HJH.0000000000003035 with permission from Wolters Kluwer Health, Inc.

Fig. 3. Relationships observed between fetal growth trajectories and adult BMI, WC and hs-CRP.

Associations observed from linear mixed modeling (Model 1) between growth trajectories (A-Abdominal circumference, B-Femur Length and C-Head Circumference) and adult outcomes (BMI- Body mass index, WC waistcircumference, hs-CRP- high sensitivity C-reactive protein). Y-axes: Standard deviation scores or z-scores for AC, FL and HC. X-axes: Gestational age in weeks. Dashed lines (--) represent the reference trajectory group while solid-bold lines (–) represent those trajectory groups having a significant association with reference group. Minus sign (−) indicates a negative association while a plus sign (+) indicates a positive association.