Prenatal smoke exposure alters growth in limb proportions and head shape in the midgestation human fetus.

The objective of this study was to examine the effects of smoke exposure on the growth patterns of the head, limbs, and torso of the midgestation human fetus. Four hundred maternal/fetal pairs contributed to this analysis: 366 individuals were assessed cross-sectionally (87 smokers and 279 nonsmokers) at approximately 20 and 32 weeks, and 34 individuals were followed longitudinally at 23, 27, and 32 weeks (10 smokers, 24 nonsmokers). Ten body parameters were measured by fetal ultrasound. In both samples, controlling for day of measurement, smoke exposure was significantly associated with early growth acceleration in head and abdominal diameters at 20-27 weeks (P < 0.05). This was followed by altered head shape (a significantly smaller biparietal to occipital frontal diameter ratio at 32 weeks, P < 0.01), and a proximal/distal growth gradient as proportionately long arms (P < 0.05 at 27 and 32 weeks) and short legs were apparent by 32 weeks, with a significant reduction in the tibia/femur ratio (P = 0.04). These fetal body growth patterns, expressed in terms of size and proportionality, are consistent with the presence of chronic hypoxia associated with maternal smoking. The growth pattern differences identify that prenatal smoking is not merely an insult resulting in consistent size and growth rate reduction across developmental ages. Instead, smoke exposure alters the growth rate of individual body segments at variable developmental stages as the fetus experiences selective growth restriction and augmentation. We hypothesize that the growth patterns observed here reflect the unique pattern of fetal blood flow favoring upper body oxygen distribution and extraction, together with genetically based adaptive strategies that permit the fetus to adjust the timing and magnitude of its growth to local environmental resources. It is possible that dolichocephaly is a previously unappreciated marker of fetal hypoxia. Reduced tibial growth may be a good marker for shortfall and a useful proxy for the adequacy of circulating resources more generally.