Maternal serum concentrations of insulin-like growth factor (IGF)-I and IGF binding protein-1 before and during pregnancy in relation to maternal body weight and composition and infant birth weight.

Maternal nutritional status, e.g. body weight and composition, is associated with fetal growth. It has been suggested that the insulin-like growth factor (IGF) system may be a mediator of this relationship. In twenty-three healthy Swedish women, we studied (1) the relationships before and during pregnancy between maternal serum concentrations of IGF-I and IGF binding protein-1 (IGFBP-1) and maternal body weight and composition; (2) interactions between serum concentrations of IGF-I (before and in early pregnancy) and maternal nutritional status in relation to infant birth weight. We found that serum IGF-I during pregnancy was positively correlated with maternal body weight (r 0.47-0.56) and fat-free body weight (r 0.61-0.65), whereas serum IGFBP-1 was negatively correlated with maternal body weight (r - 0.44 to - 0.69) and body fat (r - 0.64 to - 0.76) before and during pregnancy. Women with a lower body fat content (%) before pregnancy had greater increases in serum IGFBP-1 during pregnancy than women with a higher prepregnant body fat content (%). In addition, significant fractions of the variation in corrected infant birth weight were explained by variables related to the maternal nutritional status when these were combined with serum concentrations of IGF-I in gestational week 14 (adjusted r2 0.25-0.44, P = 0.001-0.021), but not when they were combined with such concentrations before pregnancy (adjusted r2 0.11-0.12, P = 0.105-0.121). These results suggest mechanisms by which the IGF system may be a mediator between maternal nutritional status and fetal growth.

Changes in basal metabolic rate during pregnancy in relation to changes in body weight and composition, cardiac output, insulin-like growth factor I, and thyroid hormones and in relation to fetal growth.

BACKGROUND: The total energy cost of pregnancy is largely due to an elevated basal metabolic rate (BMR). Large variations in the BMR response to pregnancy have been reported, but the factors associated with this variability are incompletely known. OBJECTIVE: The objective was to identify factors associated with variability in the BMR response to pregnancy. DESIGN: In 22 healthy women, BMR, body weight (BW), total body fat (TBF), fat-free mass (FFM), circulatory variables, serum concentrations of insulin-like growth factor I (IGF-I), and thyroid hormones were measured before pregnancy and in gestational weeks 14 and 32. BMR and BW were also measured in gestational weeks 8, 20, and 35. Fetal weight was estimated in gestational week 31. RESULTS: In gestational week 14, the increase in BMR correlated significantly with the corresponding increase in BW and with the prepregnancy percentage of TBF. Together these variables explained approximately 40% of the variability in the BMR response. In gestational week 32, the increase in BMR correlated significantly with the corresponding changes in BW, TBF, FFM, IGF-I, cardiac output, and free triiodothyronine. The increase in BW in combination with fetal weight or with the elevated concentration of IGF-I in serum explained approximately 60% of the variability in the increase in BMR. CONCLUSIONS: Weight gain and the prepregnancy percentage of TBF-ie, factors related to the maternal nutritional situation-are important factors with regard to the variability in the BMR response to pregnancy. Thus, it is important to consider the nutritional situation before and during gestation when assessing pregnancy energy requirements.

Chronic maternal feed restriction impairs growth but increases adiposity of the fetal guinea pig.

Small size at birth has been associated with an increased risk of central obesity and reduced lean body mass in adult life. This study investigated the time of onset of prenatally induced obesity, which occurs after maternal feed restriction, in the guinea pig, a species that, like the human, develops substantial adipose tissue stores before birth. We examined the effect of maternal feed restriction [70% ad libitum intake from 4 wk before to midpregnancy, then 90% until day 60 gestation (term approximately 69 days)] on fetal growth and body composition in the guinea pig. Maternal feed restriction reduced fetal (-39%) and placental (-30%) weight at 60 days gestation and reduced liver, biceps muscle, spleen, and thymus weights, relative to fetal weight, while relative weights of brain, lungs, and interscapular and retroperitoneal fat pads were increased. In the interscapular depot, maternal feed restriction decreased the volume density of multilocular fat and increased that of unilocular fat, resulting in an increased relative weight of interscapular unilocular fat. Maternal feed restriction did not alter the relative weight of perirenal fat or the volume density of adipocyte populations within the depot but increased unilocular lipid locule size. Maternal feed restriction in the guinea pig is associated with decreased weight of major organs, including liver and skeletal muscle, but increased adiposity of the fetus, with relative sparing of unilocular adipose tissue. If this early-onset obesity persists, it may contribute to the metabolic and cardiovascular dysfunction that these offspring of feed-restricted mothers develop as adults.

Postnatal oxytocin alleviates adverse effects in adult rat offspring caused by maternal malnutrition.

Repeated oxytocin administration to adult rats causes a long-term decrease of plasma levels of corticosterone and blood pressure and stimulates growth and fat retention. Maternal undernutrition increases blood pressure and plasma corticosterone in adult offspring. We hypothesized that oxytocin treatment early in life would alleviate adverse effects of intrauterine food restriction. Male pups from ad libitum-fed and food-restricted (fed 60% of ad libitum intake) dams were injected with oxytocin or saline in days 1-14 after birth. At 4 mo, blood pressure, plasma levels of corticosterone, and adiposity were assessed. Oxytocin treatment decreased blood pressure independently of nutrition, whereas the increased plasma levels of corticosterone were lowered to normal levels in food-restricted offspring. Blood pressure and adiposity were not affected by in utero food restriction, whereas birth and adult weight were. In conclusion, postnatal events may alleviate adverse effects caused by in utero food restriction. In contrast to more severe food restriction, a moderate general food restriction during gestation had no effect on blood pressure in the offspring.

Effect of maternal feed restriction during pregnancy on glucose tolerance in the adult guinea pig.

Maternal nutrient restriction and impaired fetal growth are associated with postnatal insulin resistance, hyperinsulinemia, and glucose intolerance in humans but not consistently in other species, such as the rat or sheep. We therefore determined the effect of mild (85% ad libitum intake/kg body wt) or moderate (70% ad libitum intake/kg body wt) maternal feed restriction throughout pregnancy on glucose and insulin responses to an intravenous glucose tolerance test (IVGTT) in the young adult guinea pig. Maternal feed restriction reduced birth weight (mild and moderate: both P < 0.02) in male offspring. Moderate restriction increased plasma glucose area under the curve (P < 0.04) and decreased the glucose tolerance index (K(G)) (P < 0.02) during the IVGTT in male offspring compared with those of mildly restricted but not of ad libitum-fed mothers. Moderate restriction increased fasting plasma insulin (P < 0.04, adjusted for litter size) and the insulin response to IVGTT (P < 0.001), and both moderate and mild restriction increased the insulin-to-glucose ratio during the IVGTT (P < 0.003 and P < 0.02) in male offspring. When offspring were classed into tertiles according to birth weight, glucose tolerance was not altered, but fasting insulin concentrations were increased in low compared with medium birth weight males (P < 0.03). The insulin-to-glucose ratio throughout the IVGTT was increased in low compared with medium (P < 0.01) or high (P < 0.05) birth weight males. Thus maternal feed restriction in the guinea pig restricts fetal growth and causes hyperinsulinemia in young adult male offspring, suggestive of insulin resistance. These findings suggest that mild to moderate prenatal perturbation programs postnatal glucose homeostasis adversely in the guinea pig, as in the human.

Oxytocin treatment during early life influences reproductive performance in ad libitum fed and food-restricted female rats.

Oxytocin treatment may permanently alter endocrine axes resulting in anti-stress and anabolic effects. However, the nutritional status influences the effects of oxytocin. The specific aims of this study were to investigate the effects of postnatal oxytocin treatment on reproductive performance in adult life, by studying maternal weight gain, adiposity, plasma levels of IGF-I as well as fetal and placental weights in the following groups of animals: (1) Ad libitum fed dams coming from ad libitum fed mothers. (2) Ad libitum fed dams coming from food-restricted mothers. (3) Food-restricted dams coming from ad libitum fed mothers. (4) Food-restricted dams coming from food-restricted mothers. Oxytocin treatment postnatally had long-term effects and increased adiposity in pregnant dams and stimulated placental and fetal growth relative to saline-treated dams. However, if the dams themselves had been exposed to food restriction during fetal life, the effect of postnatal oxytocin treatment changed. The oxytocin-treated mothers were still fatter but had smaller fetuses. In conclusion, postnatal oxytocin treatment influences reproductive performance in later life but is dependent on the mother's previous and current nutritional experience.