Offspring obesity risk based on metabolic subtypes in pregnant women

Varying metabolic subtypes in pregnant women lead to differences in offspring obesity risk, according to a review published in JAMA Network Open.

Childhood obesity is a condition which leads to lifelong premature morbidity. Associations have been found of maternal glucose and body mass index (BMI) with offspring adiposity and metabolic traits, indicating other glycemic and nonglycemic factors may impact fetal programming.

While studies have evaluated the link between metabolic biomarkers and offspring adiposity, they did not analyze the effects of biomarkers across classes of compounds. To examine associations between metabolic subgroup classifications and adiposity traits in offspring, investigators conducted a review of the Healthy Start Study.

The Healthy Start study was conducted from 2010 to 2014, including pregnant women aged 15 years and older with no history of still-birth, under 24 weeks’ gestation, singleton birth, and no severe preexisting chronic disease. Participants of the observational study completed in-person visits at midpregnancy, late pregnancy, delivery, and early childhood.

Data analyzed included assays from blood collected at midpregnancy and offspring anthropometry data collected during the neonatal period or childhood. There were 1325 women participating in the study.

Metabolic subgroups of women were determined using unsupervised k-means clustering. Inputs comprised 7 biomarkers at about 17 weeks’ gestation measured from fasting blood samples and 2 biomarker indices implicated in in-utero metabolic programming.

Biomarkers included glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), free fatty acids (FFAs), insulin, tumor necrosis factor α (TNF-α), and TGs:HDL-C and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).

PEA POD (Life Measurement, Inc) air displacement plethysmography was used to measure neonatal fat mass (FM) and fat free mass (FFM), with birthweight z score measured through weight at delivery and gestational age. Large-for-gestational age status was determined using national reference data.

FM and FFM were calculated through whole body air displacement plethysmography in early childhood, with FM/FMM used to calculate fat mass percentage (FM%). Covariates included maternal race and ethnicity, parity, educational attainment, dietary intake, and prenatal smoking status.

Participants had an average maternal age of 27.8 years. Of participants, 24.3% were Hispanic, 15.6% non-Hispanic Black, 53.8% non-Hispanic White, 43.6% had a college or graduate degree, 4.4% a diagnosis of gestational diabetes (GDM), 19.6% obesity before pregnancy, and 45.7% excessive weight gain during pregnancy.

About half of offspring were female, and the average birth weight was 3100 grams. About 2% were large-for-gestational age. The average early childhood visit occurred when the child was aged 4.8 years, with an average BMI for age percentile of 48.6. Obesity was seen in 6.2% of children.

Five metabolic subgroups were created. The first was a reference group including women with biomarker levels indicating a favorable metabolic profile. The second was a high HDL-C subgroup, including women with HDL-C levels considered to be anti-atherosclerotic and endothelial-protective.

The third subgroup was a dyslipidemic–high TG group, including women with atherogenic TGs:HDL-C ratio values. The fourth was a dyslipidemic–high FFA group, including women with FFAs in the 75th percentile or higher. The final subgroup was an insulin resistant (IR)–hyperglycemic group, including women with HOMA-IR values indicating insulin resistance.

Low GDM frequency and a balanced distribution of educational status was seen in the reference subgroup, and a higher quality diet and the lowest prevalence of prepregnancy obesity in the HDL-C subgroup. Women in the dyslipidemic–high TG subgroup had the highest rates of prenatal smoking, lower educational attainment, and older age. Almost half had high HOMA-IR.

FFA levels were 79.2% higher than the reference subgroup in the dyslipidemic–high FFA subgroup, but other biomarker levels were lower than the clinical threshold for metabolic risk in this group. Atherogenic lipid levels were seen in over a third of women in the IR-hyperglycemic subgroup.

Higher neonatal and childhood BMI percentile was seen in children of the IR-hyperglycemic subgroup compared to the reference subgroup. Women in the dyslipidemic–high FFA subgroup more often had children with a higher childhood FM%.

Higher FM% was also seen in children of women in the dyslipidemic–high TGs, along with higher BMI in childhood. Offspring outcomes did not differ between the high HDL-C and reference subgroups.

The risk of childhood obesity was almost 5 times higher in children born to women in the IR-hyperglycemic subgroup compared to the reference subgroup. This group also had a 9 times greater risk of high FM%. In comparison, children born to women in the dyslipidemic–high FFA subgroup were 3 times more likely of developing FM% compared to the reference group.

Reference

Francis EC, Kechris K, Jansson T, Dabelea D, Perng W. Novel metabolic subtypes in pregnant women and risk of early childhood obesity in offspring. JAMA Netw Open. 2023;6(4):e237030. doi:10.1001/jamanetworkopen.2023.7030