Medico Cirujano Y Partero

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review article
Mechanisms of Disease

Parturition
Roger Smith, M.B., B.S., Ph.D.

T

he mechanisms that instigate parturition in humans have been remarkably elusive, but some parts of the puzzle have begun to come together. A key change in the field was the realization that human parturition is a distinctly human event —animal models can reveal only limited insights. Consequently, investigators of human parturition have come to understand that they must focus on the pregnant woman, despite the ethical difficulties in conducting studies that involve women in labor. Preterm birth occurs in 5 to 15% of pregnancies, depending on the population.1 The rates are rising in many developed countries, and there is aparticularly high incidence of preterm birth among black Americans. Assisted reproduction, which can increase the frequency of multiple gestations, is only a partial explanation.2 Birth before 37 weeks of gestation is associated with 70% of neonatal deaths, and there is a strong inverse association between the perinatal death rate and the period of gestation. Infant morbidity is also related to a shortperiod of gestation. In a Swedish study, 50% of children with cerebral palsy had been born prematurely.3 Although there has been no reduction in the incidence of preterm birth over the past 30 years, the development of neonatal intensive care has improved survival considerably. The shortterm costs of neonatal intensive care are extremely high, and the long-term costs of medical and educationalservices for a child who was born prematurely make preterm birth particularly expensive.4

From the Mothers and Babies Research Centre, Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia. Address reprint requests to Dr. Smith at the Mothers and Babies Research Centre, Hunter Medical Research Institute, John Hunter Hospital, Lookout Road, Newcastle NSW 2310, Australia, or atroger. smith@newcastle.edu.au. N Engl J Med 2007;356:271-83.
Copyright © 2007 Massachusetts Medical Society.

the uniquene s s of hum a n pa r t ur i t ion
Within the class Mammalia, individual species show considerable similarity in many aspects of physiology. Reproduction, however, is an important exception. The development of a placenta is a common feature of reproduction in most mammals,but variations on the theme of parturition among placental mammals are considerable. For example, parturition in sheep is initiated by processes involving the fetal hypothalamus, pituitary, and adrenal glands,5,6 whereas parturition in goats depends on dissolution of the maternal corpus luteum.7 Haig has argued that the heterogeneity in mechanisms of parturition is due to a maternal–paternal geneticconflict8: paternal genes promote the provisioning of the fetus from maternal resources, whereas maternal genes modify fetal nutrition to preserve resources for the provisioning of later offspring, which may arise from a different father. Comparative genomic analyses have revealed that almost 95% of human and chimpanzee DNA sequences are shared,9,10 but one of the greatest differences between thetwo species occur in genes related to reproduction. In addition, striking changes in the female pelvis with the assumption of an upright posture by the human ancestor australopithecus and increases in the size of the cranium as modern humans evolved have had consequences for parturition (Fig 1).11
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n engl j med 356;3

www.nejm.org

january 18, 2007

Downloaded from www.nejm.org atHinari Phase 1 sites -- comp on January 29, 2007 . Copyright © 2007 Massachusetts Medical Society. All rights reserved.

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In humans, by contrast, the timing of birth is associated with the development of the placenta — in particular, with expression of the gene for corticotropin-releasing hormone (CRH) by the placenta.14
Maternal...