Relation of birthweight to maternal plasma glucose and insulin concentrations during normal pregnancy

Abstract

Summary.Maternal diabetes mellitus is complicated by fetal macrosomia and predisposes the offspring to diabetes, but recent evidence indicates that a low, not high, birthweight is associated with a higher incidence of Type 2 (non-insulin dependent) diabetes in adult life. To clarify the relationships between maternal glucose and insulin levels and birthweight, we measured oral glucose tolerance and neonatal weight in a large group (n = 529) of women during the 26th week of pregnancy. Women with gestational diabetes (n = 17) had more familial diabetes, higher pre-pregnancy body weight, and tended to have large-for-gestational-age babies. In contrast, women with essential hypertension (n = 10) gave birth to significantly (p < 0.01) smaller babies. In the normal group (without gestational diabetes or hypertension, n --503), maternal body weight before pregnancy and at term, maternal height, week of delivery, gender of the newborn, and parity were all significant, independent predictors of birthweight, together explaining 23 % of the variability of neonatal weight. In addition, both fasting (p < 0.006) and 2-h post-glucose (p = 0.03) maternal plasma glucose concentrations were positively associated with birthweight independent of the other physiological determinants, accounting, however, for only 10% of the explained variability. In a subgroup of 134 normal mothers with prepregnancy body mass index of less than 25 kg. m 2, in whom plasma insulin measurements were available, the insulin area-under-curve was inversely related to birthweight (p < 0.02) after simultaneously adjusting for physiological factors and glucose area. When glucose and insulin measurements were combined in the I/G ratio (ratio of insulin to glucose area), this was still inversely related to birthweight. Furthermore, maternal insulinaemia was directly related to blood pressure levels (p <0.001) independently of body weight. We conclude that in normal pregnancy, whereas physiological factors account for most of the explainable variability of infant weight, the influence of the maternal metabolic milieu is dual, positive for glucose levels but negative for insulin concentrations. Maternal hyperinsulinaemia during pregnancy may be one trait linking low birthweight with predisposition to diabetes in adult life.

Paternal insulin resistance and its association with umbilical cord insulin concentrations

“…We are uncertain why the results of this study differ from others, but it may reflect the relatively large numbers in our study, the accurate prospectively collected data using a research protocol to measure length, the mode of collection of cord samples, and the use of a specific insulin assay. As predicted, we found correlations with measures of the intrauterine environment such as maternal glycaemia, maternal insulin resistance and maternal BMI, and relationships of these factors with both cord insulin and fetal growth have been reported previously [5][6][7][8][9]. These expected findings provide validation for our insulin results.…”

“…Pedersen [4] proposed that increased fetal growth in diabetic pregnancies is due to increased insulin secretion by the fetus in response to exposure to a high maternal glucose concentration. Birthweight is directly correlated with maternal glycaemia, both fasting and stimulated glucose levels, in the non-diabetic pregnancy [5]. Other environmental factors altering fetal insulin concentrations and growth include maternal insulin sensitivity during pregnancy [6][7][8] and maternal size [9], with associations also seen with maternal nutrition [10], parity [10,11], and social class [10].…”

The Impact of Maternal Glycemia and Obesity on Early Postnatal Growth in a Nondiabetic Caucasian Population

“…In keeping with other studies (15)(16)(17)(18), we demonstrated maternal glycemia within the normal range was correlated with parameters of fetal growth at birth, including weight, length, and BMI. This effect is most pronounced in the mothers in the upper tertile of glycemic values, suggesting the macrosomia seen in pregnancies complicated by type 2, or gestational, diabetes may be a continuum of the effect of "normal" glucose on birth weight in the nondiabetic pregnancy.…”

“…Insulin-mediated growth of the fetus reflects maternal glycemia, with birth weight being increased in diabetic pregnancies, and correlates with maternal glycemia, in both fasting and stimulated levels, in the nondiabetic pregnancy (15)(16)(17)(18). The impact of glycemia within the normal range on early postnatal growth in European Caucasians is uncertain.…”

Sex of the baby and risk of gestational diabetes mellitus in the mother: a systematic review and meta-analysis

“…The 20 studies [1,3,4,[14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] that met inclusion criteria provide data on 2,402,643 women. A study from Retnakaran and Shah [4] evaluated the risk for GDM conferred by fetal sex in a first pregnancy and, in those women in whom it was applicable, the analogous risk in a second pregnancy such that, in the pooled analyses, the first and second pregnancies from this study were entered as two separate reports.…”