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Background: Maternal smoking during pregnancy is associated with a reduction in birth size. Very few studies have collated changes in fetal biometry, neonatal anthropometry, biochemical factors involved in fetal growth, and measures of uterine and umbilical blood flow.Methods: We related smoking status in 1650 low-risk, singleton Caucasian pregnancies delivering at term to measures of fetal growth, uterine and umbilical artery blood flow, placental appearance, birth size, and cord concentrations of IGF-I and - II and IGF binding protein (IGFBP)-3.Results: Mothers who smoked in pregnancy were younger ( P < 0.001) and shorter ( P = 0.03) and from lower socioeconomic groups ( P < 0.001). Mean umbilical artery blood flow at 20 wk gestation was not associated with smoking status but was significantly higher in smokers at 30 wk ( P = 0.006). Uterine artery blood flow was unaffected. Smoking was associated with an increase in the percentage of abnormal placentas in a dose-dependent manner and with a 3.1-fold increased risk ( odds ratio 3.1, 95% confidence interval 1.3 - 7.6) of abnormal umbilical artery blood flow ( P = 0.009). Smoking was associated with a reduction in fetal femur length ( P = 0.005) and abdominal circumference as well as birth weight, length, and head circumference but not skinfold thickness. Cord plasma concentrations of IGF-I and IGFBP-3 were lower in the babies of mothers who had smoked ( P = 0.02 and P = 0.01, respectively).Conclusion: We concluded that maternal smoking is associated with an altered placental appearance on ultrasonography, increased umbilical artery blood flow resistance, and a reduction in longitudinal and intraabdominal organ growth. Circulating concentrations of IGF-I and IGFBP-3 along with measures of birth size but not markers of body fat are reduced, suggesting smoking results in a reduction in organ size and function.

In rodents and humans there is a sexually dimorphic pattern of GH secretion that influences the serum concentration of IGF-I. Pattern differences can be identified in children, but it is not known how early this difference is established. We studied the plasma concentrations of IGF-I, IGF-II, IGF-binding protein-3 (BP-3), and GH in cord blood taken from the offspring of 1650 singleton Caucasian pregnancies born at term and related these values to birth weight, length, and head circumference. Pregnancies complicated by preterm delivery, antepartum hemorrhage, pregnancy-induced hypertension, preeclampsia, or gestational diabetes and where cigarette smoking continued were excluded, resulting in a cohort of 987. Cord plasma concentrations of IGF-I, IGF-II, and IGFBP-3 were influenced by factors influencing birth size: gestational age at delivery, mode of delivery, maternal height, and parity of the mother. Plasma GH concentrations were inversely related to the plasma concentrations of IGF-I and IGFBP-3; 10.2% of the variability in cord plasma IGF-I concentration and 2.7% for IGFBP-3 was explained by sex of the offspring and parity. None of the factors, apart from maternal height, influenced cord serum IGF-II concentrations (adjusted r(2) = 1%). Sex of the baby, mode of delivery, and parity influenced cord serum GH concentrations (adjusted r(2) = 2.6%). Birth weight, length, and head circumference measurements were greater in males than females (P < 0.001). Mean cord plasma concentrations of IGF-I (males, 66.4 +/- 1.2 micro g/liter; females, 74.5 +/- 1.3 micro g/liter; P < 0.001) and IGFBP-3 (males, 910 +/- 13 micro g/liter; females 978 +/- 13 micro g/liter; P < 0.001) were significantly lower in males than females. Cord plasma GH concentrations were higher in males than females (males, 30.0 +/- 1.2 mU/liter; females, 26.9 +/- 1.1 mU/liter; P = 0.05), but no difference was noted between the sexes for IGF-II (males, 508 +/- 6 micro g/liter; females, 519 +/- 6 micro g/liter; P = NS). After adjustment for gestational age, parity, and maternal height, cord plasma concentrations of IGF-I and IGFBP-3 along with sex explained 38.0% of the variability in birth weight, 25.0% in birth length, and 22.7% in head circumference. These data demonstrate that in a group of singleton Caucasian babies born at term, cord plasma IGF-I, IGFBP-3, and GH concentrations relate to birth size, with evidence for sexual dimorphism in the GH-IGF axis.