Results
Figure 1 shows the flow diagram of mother-child pairs’
selection procedure(power calculation provided in supplementary file
S1). The baseline characteristics of participants are shown inTable 1 . The majority(91.20%) of maternal blood samples were
collected after overnight fasting. Maternal mid-pregnancy weight,
fasting glucose, and lipids profile were measured at a mean of
20.0(SD=4.0), 24.6(SD=1.4), and 20.5(SD=3.5) gestation weeks,
respectively. Cord blood samples were stored for a median of 488(IQR 394
to 707) days before analysis.
Association of maternal metabolic parameters with
birthweight and
CBI
Table 2 presents the associations between the association of
maternal pre-pregnancy BMI, GWG, and maternal mid-pregnancy fasting
glucose/HDL-C/TG levels with neonatal outcomes. Pre-pregnancy
BMI(adjustedβ=29.25, 95%CI: 22.77 to 35.73g per
Kg/m2), GWG(adjustedβ =18.75, 95%CI: 13.06 to 24.43g
per Kg), fasting glucose(adjustedβ=84.32, 95%CI: 42.65 to 125.98g per
mmol/L), and triglycerides(adjustedβ=67.97, 95%CI: 42.38 to 93.55g per
mmol/L) were positively associated with birthweight, while HDL-C was
negatively associated with birthweight(adjustedβ=45.78, 95%CI: 5.59 to
85.97g per mmol/L). There was no evidence of an association between
maternal TC and LDL-C levels and birthweight(Supplementary file S6).
Elevated maternal pre-pregnancy BMI, early GWG, fasting blood glucose
and triglycerides level were significantly associated with an increased
risk of LGA. The risk was particularly high for fasting glucose(OR=2.06,
95%CI 1.31 to 3.24). Higher pre-pregnancy BMI and triglycerides were
significantly associated with lower odds of SGA. There was no evidence
of an association between maternal HDL-C level and risk of LGA/SGA.
Maternal fasting glucose(adjustedβ=2.23, 95%CI: 0.89 to 3.57 μU/ml per
mmol/L) and triglycerides levels(adjustedβ=0.88, 95%CI: 0.05 to 1.71
μU/ml per mmol/L) were significantly associated with higher CBI.
Pre-pregnancy BMI, GWG, TC, and LDL-C levels did not show an association
with CBI(Table 2 and Supplementary file S6).
Association of maternal metabolic parameter Z-scores with
birthweight and CBMI
Z-scores
Table 3 shows the estimates of the association of maternal
metabolic parameter Z-Scores with birthweight Z-Score and CBI Z-Score,
and subgroup estimates for boys and girls. Maternal pre-pregnancy
BMI(adjustedβ=0.20, 95%CI 0.15 to 0.24), early GWG(adjustedβ=0.17,
95%CI 0.12 to 0.22), triglycerides(adjustedβ=0.12, 95%CI 0.08 to
0.16), and glucose(adjustedβ=0.08, 95%CI 0.04 to 0.12) Z-scores had
positive associations with birthweight Z-Score. Maternal HDL-C Z-Score
showed a negative association with birthweight Z-Score in boys(adjusted
β=-0.06, 95%CI -0.12 to -0.01) only. The association of pre-pregnancy
BMI, GWG, glucose, and triglycerides Z-Scores with birthweight Z-Score
remained statistically significant after adjusting for other four
maternal metabolic risk factors.
Maternal glucose Z-Score(adjustedβ=0.13, 95%CI 0.08 to 0.18) appears to
be the most important contributor to CBI Z-Score in both boys and girls.
Both maternal pre-pregnancy BMI(adjustedβ=0.10, 95%CI 0.05 to 0.15) and
triglycerides(adjustedβ=0.06, 95%CI 0.01 to 0.11) Z-Scores showed
positive associations with CBI Z-Score. No statistically significant
association was observed between maternal early GWG and HDL-C Z-Scores
with CBI Z-Score.
ABN analysis results for interdependent maternal metabolic
parameters
Figure 2 shows the optimal summary DAGs inferred by ABN
analysis(Supplementary file S5). The adjusted regression coefficients(β)
in the graph represent how much the dependent variable changes per unit
increase in the independent variable. Maternal pre-pregnancy BMI
appeared to be the most influential upstream factor for both maternal
metabolic parameters in pregnancy(glycaemia: β=0.14, 95%CI 0.09 to
0.19; early GWG: β=-0.12, 95%CI -0.17 to -0.06; triglycerides: β=0.23,
95%CI 0.18 to 0.28; HDL-C: β=-0.12, 95%CI -0.17 to -0.07) and
birthweight(β=0.27, 95%CI 0.22 to 0.32). An indirect effect on neonatal
insulin secretion was also observed. Our DAGs results showed that
maternal glycaemia was associated with CBI(β=0.12, 95%CI 0.07 to 0.17).
Birthweight was also associated with CBI(β=0.24, 95%CI 0.19 to 0.29).
Neither triglycerides nor HDL-C were linked to birthweight or CBI.