Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

How hypoxia slows fetal growth: insights from high altitude

A continuous oxygen supply is vital for fueling fetal growth, yet we know surprisingly little as to the precise mechanisms by which hypoxia reduces fetal growth. Animal models, while important, are limited by the enormous variability in mammalian physiologic responses to pregnancy. One of the earliest models for understanding hypoxia-induced reductions in fetal growth came from studies at high altitude that showed high altitude to have one of the strongest depressant effects on fetal growth. But all populations are not equally affected. Dolma et al. have added valuable information now showing that that Ladakhis, like Tibetans and Andeans, have a lower-than-expected frequency of small-for-gestational age (SGA) infants. Consistent with previous reports, these authors also found that uterine artery diameters at mid pregnancy (weeks 26–28) were larger in women giving birth to appropriate-for-gestational age (AGA) than SGA infants at high but, interestingly, not at low altitude. Much remains to be learned about the physiologic pathways by which hypoxia impairs fetal growth. The variability among high-altitude populations and increasing sophistication of tools for investigating causal mechanisms have the potential to expand our presently limited means for identifying new treatments for hypoxia-related complications of pregnancy and fetal life.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Jensen, G. M. & Moore, L. G. The effect of high altitude and other risk factors on birthweight: independent or interactive effects? Am. J. Public Health 87, 1003–1007 (1997).

    CAS  Article  Google Scholar 

  2. 2.

    Julian, C. G., Hageman, J. L., Wilson, M. J., Vargas, E. & Moore, L. G. Lowland origin women raised at high altitude are not protected against lower uteroplacental O2 delivery during pregnancy or reduced birth weight. Am. J. Hum. Biol. 23, 509–516 (2011).

    Article  Google Scholar 

  3. 3.

    Julian, C. G. et al. Lower uterine artery blood flow and higher endothelin relative to nitric oxide metabolite levels are associated with reductions in birth weight at high altitude. Am. J. Physiol. 295, R906–R915 (2008).

    CAS  Google Scholar 

  4. 4.

    Julian, C. G. et al. Augmented uterine artery blood flow and oxygen delivery protect Andeans from altitude-associated reductions in fetal growth. Am. J. Physiol. 296, R1564–R1575 (2009).

    CAS  Google Scholar 

  5. 5.

    Zamudio, S. et al. Maternal oxygen delivery is not related to altitude- and ancestry-associated differences in human fetal growth. J. Physiol. 582, 883–895 (2007).

    CAS  Article  Google Scholar 

  6. 6.

    Unger, C., Weiser, J. K., McCullough, R. E., Keefer, S. & Moore, L. G. Altitude, low birth weight, and infant mortality in Colorado. JAMA 259, 3427–3432 (1988).

    CAS  Article  Google Scholar 

  7. 7.

    Lorca, R. et al. Chronic hypoxia reduces NO-dependent myometrial artery vasodilator response during pregnancy. Hypertension 73, 1319–1326 (2019).

  8. 8.

    Keyes, L. E., Majack, R., Dempsey, E. C. & Moore, L. G. Pregnancy stimulation of DNA synthesis and uterine blood flow in the guinea pig. Pediatr. Res. 41, 708–715 (1997).

    CAS  Article  Google Scholar 

  9. 9.

    Osol, G. & Moore, L. G. Maternal uterine vascular remodeling during pregnancy. Microcirculation 21, 38–47 (2014).

    Article  Google Scholar 

  10. 10.

    Hale, S. A. et al. Sildenafil increases uterine blood flow in nonpregnant nulliparous women. Reprod. Sci. 17, 358–365 (2010).

    CAS  Article  Google Scholar 

  11. 11.

    Pels, A. et al. Maternal sildenafil vs placebo in pregnant women with severe early-onset fetal growth restriction: a randomized clinical trial. JAMA Netw. Open 3, e205323 (2020).

    Article  Google Scholar 

  12. 12.

    Askie, L. M., Duley, L., Henderson-Smart, D. J., Stewart, L. A. & Group, P. C. Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data. Lancet 369, 1791–1798 (2007).

    CAS  Article  Google Scholar 

  13. 13.

    Duley, L. Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Caribbean. Br. J. Obstet. Gynaecol. 99, 547–553 (1992).

    CAS  Article  Google Scholar 

Download references

Funding

This work was funded by NIH HD088590 and NIH HL138181.

Author information

Affiliations

Authors

Contributions

L.G.M. conceived of, drafted, revised, and approved the commentary submitted.

Corresponding author

Correspondence to Lorna G. Moore.

Ethics declarations

Competing interests

The author declares no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Moore, L.G. How hypoxia slows fetal growth: insights from high altitude. Pediatr Res (2021). https://doi.org/10.1038/s41390-021-01784-0

Download citation

Search

Quick links