Is preterm labor evolutionarily beneficial?

26 Nov

I would like to pose the question, is preterm labor reproductively beneficial in the sense of favoring propagation of the species over the long haul.

Normal labor in the sheep occurs when fetal maturation increases fetal cortisol production, changing the estrogen/progesterone ratio in mom’s blood leading to a change in myometrial cell phenotype and the onset of labor. Primates threw a wrench in the mechanism with the fetal adrenal which produces DHEA throughout pregnancy. This additional mechanism probably evolved because all primates are born more or less premature.  Challis and others have tried to tease out the primate mechanism of term labor, but the core concept is, as it is in the sheep, that labor ensues because of a fetal signal of maturity[1].

If the fetus was becoming undernourished or hypoxic in utero, survival might be enhanced by delivery if not too preterm. Such a fetal signal of distress might logically hijack the normal signaling of fetal maturation. There is not a great deal of evidence for this.  Naeye in his summary of the perinatal collaborative study felt that uneven villous maturation as a surrogate for decreased utero-placental blood flow was a significant predictor of preterm labor [2]. A study found two groups of preterm labor placentas, those with chorioamnionitis and those with villous evidence of ischemia[3].  I think I see this dichotomous pattern (with overlap) in routine examination of spontaneous non-preeclamptic preterm placentas. There is also not a great deal of clinical evidence for utero-placental ischemia causing preterm labor. A prospective study of  growth restricted fetuses based on femur length/ abdominal circumference ratio did not show a decrease in preterm delivery with treated preterm labor in the thin fetuses despite an earlier retrospective study  that did show such a relationship [4, 5]. As an obstetrical resident I remember being taught that preterm labor was more common in preeclampsia or at least that such patients were easier to induce. I quick search of the literature did not find any studies, and with almost universal treatment and early delivery if indicated of severe preeclampsia patients, it would be difficult to do a study now. From autopsies, we know all too well that lethal fetal growth restriction with multiple placental infarctions can continue without labor until the infant dies in utero.   If a mechanism of fetal induced preterm labor exists it might lower maternal estriol levels via the fetal adrenal placenta axis.

Some fetal stress is associated with hydrops and hence polyhydramnios which likely operates by the effect of stretch on the uterus. Experimentally, a balloon inflated in a rat uterine horn induces myometrial gap junctions in that horn[6]. There is clinical evidence that pregnancies that overstretch the uterus are more likely to deliver earlier such pregnancies with multigestation and polyhydramnios. The evolutionary advantage of this mechanism would be that it protects the mother and perhaps helps fetal survival. Stretch may also be a mechanism to amplify the normal signals of labor within the uterus starting in  an area of local contraction.

Clearly there are situations in which early delivery of the infant even if it caused fetal death that would be beneficial from the longer perspective of reproductive success if delivery permitted the mother to survive to reproduce at a more favorable time. Examples might be as obvious as intrauterine infection to more subtle such as the need to migrate with the herd, or with rats to mate with a new dominant male. Certainly inflammatory mediators such as prostaglandins would be one likely mechanism to induce labor, and the success of prostaglandin analogs inducing labor in clinical practice supports this idea.  To understand human preterm labor due to maternal auto-induction of labor, a better knowledge of factors in other animals and their mechanisms might be helpful. Often this mechanism of preterm labor is said to be caused by chorioamnionitis.  I think it is disingenuous to say that chorioamnionitis is a cause of preterm labor without being able to explain why some patients are susceptible to chorioamnionitis. One could argue that preterm labor from ascending vaginal micro-organisms might be part of the mechanism of preterm labor. For example some stress elevates maternal inflammatory mediators which cause cervical ripening that leads to chorioamnionitis that produces the intense amplification of the inflammatory signal and leads to labor.

Such ideas about the evolution of preterm labor are pure speculation without knowledge of the comparative biology of preterm labor. I know that horses can get ordinary human-like ascending chorioamnionitis (really allantoic-chorioamnionitis) and that cows suffer from motile trichomonad infection causing fetal loss[7], but I don’t really know anything about the risk factors in the wild or the barnyard.  I do not know the biological ecology of preterm labor or the phylogenetic origin of the mechanism of preterm labor. I don’t even know if other primates have a problem with spontaneous preterm labor?

Some of you out there must be better biologists than I am. What is known about comparative preterm labor?

 

 

1.            Challis, J.R., et al., Understanding preterm labor. Ann N Y Acad Sci, 2001. 943: p. 225-34.

2.            Naeye, R.L., Disorders of the Placenta, Fetus and Neonate, Diagnosis and Clinical Significance. 1992, St. Louis: Mosby Year Book.

3.            Arias, F., et al., Maternal placental vasculopathy and infection: Two distinct subgroups among patients with preterm labor and preterm ruptured membranes. Am J Obstet Gynecol, 1993. 168: p. 585-91.

4.            Westgren, M., et al., Fetal femur length/abdominal circumference ratio in preterm labor patients with and without successful tocolytic therapy. J Ultrasound Med, 1986. 5(5): p. 243-5.

5.            Beall, M.H. and L.D. Platt, A prospective trial of the femur length to abdominal circumference ratio to predict the outcome of preterm labor. Am J Perinatol, 1989. 6(3): p. 284-6.

6.            Wathes, D.C. and D.G. Porter, Effect of uterine distension and oestrogen treatment on gap junction formation in the myometrium of the rat. J Reprod Fertil, 1982. 65(2): p. 497-505.

7.            Rhyan, J.C., L.L. Stackhouse, and W.J. Quinn, Fetal and placental lesions in bovine abortion due to Tritrichomonas foetus. Vet Pathol, 1988. 25(5): p. 350-5.

 

 

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