Fetal growth: too little or just right?

Fetal somatic growth rate is a controlled variable that is not completely understood. While we do not fully understand the mechanisms by which the growth rate is controlled (i.e. how or whether fetal body mass is sensed, what might constitute the ‘set‐point’ for the control mechanism, and how growth is accelerated or decelerated to match a ‘normal’ growth rate), we do understand several variables that affect the rate of fetal somatic growth. Importantly, the availability of metabolic substrate (nutrients, blood gases) is an important limitation to fetal growth, and it is generally accepted that many forms of intrauterine growth restriction (IUGR) have as a mechanism reduced supply of nutrients (e.g. glucose, amino acids). We also understand several of the molecular signalling mechanisms influencing the rate of fetal somatic growth, most notably the insulin‐like growth factors (IGF‐1 and IGF‐2). While our knowledge of fetal growth rate is limited to identification of important variables influencing growth rate, we have begun to understand the biological costs of IUGR. The landmark epidemiological studies performed by David Barker and colleagues have identified morbid long‐term risks of low birthweight, including an increased probability of coronary artery disease, hypertension, obesity and hypertension in adults who started life as small birthweight babies (Barker et al. 1989). Rapid catch‐up growth postnatally in the IUGR babies may be an important factor with regard to the severity of programmed adult disease (Eriksson et al. 1999).

In this issue of The Journal of Physiology, the article entitled ‘Postnatal effects of intrauterine treatment of the growth‐restricted ovine fetus with intra‐amniotic insulin‐like growth factor‐1’, by Spiroski, Oliver, Jaquiery, Prickett, Espiner, Harding, and Bloomfield addresses what is perhaps the most salient question about IUGR and its associated morbidities: is there a possible therapeutic strategy that can remedy the low birth weight and reduce the tendency for catch‐up growth? Building on earlier reports that intra‐amniotic injections of IGF‐1 increase birth weight (Eremia et al. 2007; Wali et al. 2012), this group of investigators administered IGF‐1 into the amniotic fluid in a sheep model of IUGR. They report that in addition to the increased birth weight caused by IGF‐1 treatments, the postnatal growth rates were reduced. The effect of IGF‐1 to normalize or at least partially normalize postnatal growth rates appears to be partially accounted for by the increased birthweight. Nevertheless, the effect of the prenatal IGF‐1 treatment has an effect on growth that persists throughout the first 2 weeks of postnatal life. The prenatal IGF‐1 treatment appears to generate a growth pattern that persists after discontinuation of treatment. The effect of the IGF‐1 on body mass appears to be different in males compared to females, suggesting an endocrine action that is modified by sex‐specific gene expression in the growing fetus and neonate.

The work of Spiroski and colleagues (2018) adds new dimensions to our understanding of nutrient restriction and IUGR. From a purely scientific perspective, this work adds a dimension of time: prenatal treatment with IGF‐1 appears to bend the arc of growth long after discontinuation of treatment. From a theoretical perspective, does prenatal IGF‐1 partially correct the ‘error signal’ (compared to normal birth weight) in a biological control mechanism controlling growth patterns, and is that why postnatal growth is slowed by IGF‐1? And from a purely practical perspective, regardless of mechanism, have these investigators found a potential therapy that can prevent IUGR and avoid the long‐term programming effects associated with fetuses that would otherwise be destined to be IUGR babies?

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Competing interests

None declared.