Abstract
Research questionDoes maternal preconception insulin resistance affect neonatal birth weight among women with obesity? Is insulin resistance associated with circulating bile acids? Do bile acids influence the association between maternal preconception insulin resistance and neonatal birth weight? DesignAn exploratory post-hoc analysis of the LIFEstyle randomized controlled trial comparing lifestyle intervention with conventional infertility treatment in women with a BMI of ≥29 kg/m2. Fasting blood samples were collected at randomization and after 3 and 6 months in 469 women. Insulin resistance was quantified using the homeostasis model assessment of insulin resistance (HOMA-IR). Bile acid sub-species were determined by liquid chromatography with tandem mass spectrometry. Singletons were included (n = 238). Birth weight Z-scores were adjusted for age, offspring gender and parity. Multilevel analysis and linear regressions were used. ResultsA total of 913 pairs of simultaneous preconception HOMA-IR (median [Q25; Q75]: 2.96 [2.07; 4.16]) and total bile acid measurements (1.79 [1.10; 2.94]) µmol/l were taken. Preconception HOMA-IR was positively associated with total bile acids (adjusted B 0.15; 95% CI 0.09 to 0.22; P < 0.001) and all bile acid sub-species. At the last measurement before pregnancy, HOMA-IR (2.71 [1.91; 3.74]) was positively related to birth weight Z-score (mean ± SD 0.4 ± 1.1; adjusted B 0.08; 95% CI 0.01 to 0.14; P = 0.03). None of the preconception bile acids measured were associated with birth weight. ConclusionMaternal preconception insulin resistance is an important determinant of neonatal birth weight in women with obesity, whereas preconception bile acids are not.
Highlights
During pregnancy, the development of insulin resistance is a normal physiological adaptation necessary to meet the nutritional requirements of the growing fetus and placenta (King, 2000)
Preconception homeostasis model assessment of insulin resistance (HOMA-IR) was positively associated with total bile acids and all bile acid sub-species
Maternal preconception insulin resistance is an important determinant of neonatal birth weight in women with obesity, whereas preconception bile acids are not
Summary
The development of insulin resistance is a normal physiological adaptation necessary to meet the nutritional requirements of the growing fetus and placenta (King, 2000). The biological relevance of this adaptation is illustrated by data showing that, in uncomplicated pregnancies, maternal insulin resistance in mid-pregnancy is positively associated with neonatal birth weight (Yamashita et al, 2014). Studies exploring the association between pre-existing maternal insulin resistance before pregnancy and neonatal birth weight, are scarce. Maternal insulin resistance affects fetal growth during pregnancy and birth weight, the physiological mechanisms behind the development of insulin resistance before and during pregnancy have been insufficiently characterized (Das et al, 2010; Yamashita et al, 2014; Farrar et al, 2016)
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