Impact of maternal fasting blood glucose in pregnancy on body composition, anthropometric, and metabolic outcomes in newborns and 3-Year-Old offspring: results from the lifestyle in pregnancy and offspring study.

Higher maternal fasting plasma glucose at 28 weeks was associated with higher birth weight z-score in newborns.

• Maternal fasting plasma glucose was measured at 28 weeks gestation and analyzed both continuously and across thresholds from 4.6 to 5.8 mmol/L
• Regression models were adjusted for maternal age and pre-pregnancy BMI
• The association was observed when analyzing glucose as a continuous measure
• The study included 301 women from the Lifestyle in Pregnancy (LiP) study

A maternal fasting glucose threshold of ≥5.6 mmol/L predicted higher birth weight and increased large-for-gestational-age (LGA) risk.

• Threshold analyses were conducted across cut-offs ranging from 4.6 to 5.8 mmol/L
• The 5.6 mmol/L threshold corresponds to one of the internationally used diagnostic cut-offs for gestational diabetes mellitus
• This threshold was specifically associated with both higher birth weight and increased LGA risk among the thresholds tested
• The finding supports the clinical relevance of the 5.6 mmol/L cut-off for neonatal outcomes

A maternal fasting glucose threshold of ≥5.3 mmol/L predicted higher cord c-peptide levels.

• Cord c-peptide was used as a marker of fetal insulin secretion and neonatal metabolic exposure
• The 5.3 mmol/L threshold was identified as the relevant cut-off for this outcome, lower than the threshold for LGA
• No threshold below 5.3 mmol/L was associated with cord c-peptide differences
• This finding suggests fetal hyperinsulinism may occur at lower maternal glucose levels than those producing macrosomia

At 3 years of age, no significant associations were found between maternal fasting glucose and offspring BMI z-score or metabolic markers.

• Of 301 women in the LiP study, 157 participated in the 3-year follow-up LiPO study, and 75 children had DXA assessments
• Offspring outcomes at 3 years included BMI z-score, fat and fat-free mass, lipids, and blood pressure
• Small, non-significant trends toward higher fat and fat-free mass were observed at 3 years
• No glucose threshold was linked to metabolic differences at 3 years of age

The study population showed substantial attrition from the original LiP cohort to the 3-year LiPO follow-up, with only a subset having DXA assessments.

• 301 women were enrolled in the original LiP study
• 157 women (approximately 52%) participated in the LiPO 3-year follow-up
• Only 75 children (approximately 25% of the original cohort) had DXA body composition assessments at 3 years
• This attrition may limit the statistical power to detect associations at 3 years

Diagnostic fasting glucose thresholds vary internationally, creating uncertainty about which cut-offs best predict offspring outcomes.

• The study analyzed thresholds ranging from 4.6 to 5.8 mmol/L to capture the range of internationally used diagnostic criteria
• Different international guidelines use varying fasting glucose cut-offs for gestational diabetes mellitus diagnosis
• The study was motivated in part by this international variation in diagnostic thresholds
• Results showed that different thresholds (5.3 and 5.6 mmol/L) were relevant for different outcomes (cord c-peptide vs. birth weight/LGA)

The authors concluded that longer-term follow-up is needed to determine whether mild maternal hyperglycemia has later metabolic consequences in offspring.

• The ongoing 15-year LiP data collection was cited as the next step for answering this question
• The 3-year follow-up may be insufficient to detect metabolic consequences of mild maternal hyperglycemia
• Non-significant trends toward higher fat and fat-free mass at 3 years were noted as potentially meaningful with longer follow-up
• The authors characterized the 3-year findings as inconclusive rather than definitively negative for longer-term metabolic risk