Fetal adaptation to stress: Part I: acceleration of fetal maturation and earlier birth triggered by placental insufficiency in humans

doi:10.1016/j.earlhumdev.2004.03.002

Early Human Development

Volume 78, Issue 1, June 2004, Pages 15-27

https://doi.org/10.1016/j.earlhumdev.2004.03.002 Get rights and content

Abstract

This review is an attempt to provide an integrative view for the biological changes triggered by fetal stress through a multidisciplinary approach. Acceleration of brain and lung maturation in certain risk pregnancies was first described clinically and confirmed by biochemical, electrophysiological and experimental data. Moreover, new experimental findings suggest that a fetal clock centrally mediated by fetal nutritional status could determine timing of parturition. However, some skepticism persisted about the usefulness of this body of knowledge for obstetrical management in developed countries. The interest concerning this adaptation to intrauterine stress was later renewed from various sources, as developed in Part II.

Introduction

Fetal stress has been a hot topic for decades, an important issue for both obstetricians and neonatologists in the peripartum management of the mother and infant. It has become clear recently that the effects of fetal stress, both short term and long term, both beneficial and adverse, are not only of interest for perinatology but also for evolutionary biology, for neurology and for adult medicine. This general review represents an attempt to bring together data from several disciplines, including authors from obstetrics, pediatric neurology, pediatric pulmonology and animal biology.

This review is presented in two parts: clinical data will be discussed in Part I: acceleration of maturation may occur in brain and lungs, as an adaptation to fetal stress. Early initiation of parturition may also be associated. These adaptive changes could represent a life-saving answer to moderate stress with resultant earlier birth of a more mature newborn, and increased survival as long as the unfavorable fetal environment is not too early or too severe.

Evolutionary aspects, experimental and epidemiological data on adult health will be discussed in Part II. The capacity to vary development in response to the environment is demonstrated in amphibians, in which the neuroendocrine stress system has been studied, with corticotropin releasing hormone as the primary player. Adverse long-term effects on hippocampal neurons have been studied in rats, as a consequence of prenatal stress. Finally, a new field of investigation opened in the 1990s with the Barker hypothesis, suggesting long-term effects of fetal undernutrition on the determination of chronic adult diseases.

Section snippets

Possible fetal adaptation to unfavorable circumstances

Questioning the so-called clockwork precision in fetal maturation was not politically correct in the 1960s as clinical dating in neonates relied on this postulated precision and has been accepted for 20 years. Some doubts however arose about the immutability of developmental processes with precise documentation of ovulation based on temperature curves and later by pregnancies obtained by stimulation of ovulation.

The first break in this dogma was the discovery by Gluck and Kulovich in 1973 [1],

Neurological assessment of maturation: methodological issues

Neurological assessment of maturation from 28 to 40 weeks gestation was initiated by Saint-Anne-Dargassies [17], [18] and later used and modified in various ways. The personal goal of one of us (Amiel-Tison) has been to select the most useful neurological criteria and to describe and illustrate the infant responses to make the exam both more appealing to clinicians and more reliable [19]. Additional simplification has resulted in a 10-item table (Table 1) [20], [21]. The originality of this

Are adaptive changes observed in the lung ?

During the 1970s and 1980s, a low incidence of respiratory distress syndrome (RDS) in neonates having experienced a shortage of nutrients such as in multiple pregnancies for instance [5] was observed. Within this period, biological observations tend to show that the L/S ratio in amniotic fluid was reaching mature levels earlier in maternal hypertensive pregnancies [30] as well as in twin pregnancies [31], therefore tending to demonstrate an accelerated fetal lung maturation (FLM). This

Natural history in pregnancy induced hypertension

It is necessary to go back to the natural history of preeclampsia, before modern management modified its spontaneous evolution; this means back to the 1960s, a time when the disease was well described but the therapeutic approach timid, when early CS for fetal rescue was not performed. Based on the Cleveland survey (1962–1968) [47] toxemic patients have a tendency to deliver earlier, as shown in Fig. 1, when comparing the birth frequency distribution for all primigravidae with that of

Conclusion

Conceptually new in the early 1970s, fetal adaptation to stress is now relying on various experimental data. However, uncertainties concerning a probable threshold (a GA below which adaptation does not occur) and the lack of biological criteria available during pregnancy are still responsible for skepticism about the usefulness of this body of knowledge for obstetrical management.

Since long ago, pediatricians were aware of remarkable survival in very preterm and very thin neonates who manage to

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These findings support the hypothesis that placental-derived CRH stimulates the release of fetal pituitary adrenocorticotropin (ACTH) to enhance fetal adrenal cortisol production which further stimulates placental CRH release. An important role of the fetus in stress-induced PTB has been recently proposed.77–79 Through the production of adrenal hormonal precursors, data supports the theory that the fetus actively participates in controlling the timing of labor.80
Prematurity is a devastating disease with high neonatal morbidity and mortality based on gestational age at birth. Genetic and hormonal signals impact directly on the maternal predisposition to preterm birth or sudden onset of myometrial contractility. Candidate gene or genome-wide approaches are beginning to identify potential variants for women at risk for premature delivery or increased responsiveness to hormonal signals including progesterone. However, a majority of these studies have not yielded definitive results to allow for at this stage for development of personalized therapy.
Relation between maternal antenatal anxiety and infants' weight depends on infants' sex: A longitudinal study from late gestation to 1-month post birth
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First, our data suggest that even mild anxiety influences fetal growth, thus showing again that stress-related modulation of fetal growth is not limited to severe conditions [63]. Second, our results suggest that fetal development can be accelerated in the context of mild challenge as has been reported in a few previous studies [48,52,64]. Third, it is important to point out that although effect sizes were small; even subtle deviations in infants' weight at birth can have significant long term detrimental effects on development, including cognitive development and educational achievement during childhood and on adults' response to stress and physical and mental health up to and beyond middle-age [[65–67]; reviews in [68–70]].
To test for gender-differences in the relation between mothers' antenatal anxiety and infants' body weight during gestation, at birth, and at 1-month of age.
Two hundred and twelve randomly-recruited women were divided into two groups: Controls (n = 105) and Anxious Group (n = 107) based on a standard cut-off of the Beck Anxiety Inventory. Outcome measures were Fetal Weight derived from biometrics obtained from an ultrasound scan in the 3rd trimester and infants' weight at birth and at 1-month of age, both obtained from medical records.
Multivariate analyses showed main effects of Gender on infants' birth weight (P = .001) and on infants' weight at 1-month of age (P = .004), but no main effects of Anxiety Group at any time-point. Gender x Anxiety Group interactions at all three time points (Fetal weight: P = .05; Birth weight: P = .03; 1-month of age: P = .10) reflected gender differences (males > females) among infants in the anxious group, but not among controls. Distinct trends regarding same sex comparisons across groups (Control vs. Anxiety) were in line with predictions (male controls < male anxious; female controls > females anxious). Controlling for Postpartum Anxiety and Antenatal and Postpartum Depression in the models did not affect primary results.
Gender differences in fetal and birth weight were more substantial among infants of anxious mothers than among controls due to the seemingly accelerated growth of “anxious” males and the diminution of weight among “anxious” females.
Parturition
2015, Knobil and Neill's Physiology of Reproduction: Two-Volume Set
The success of pregnancy depends on the appropriate process and timing of parturition. For each viviparous species, natural selection has affected extant physiology such that birth processes and timing complement overall reproductive strategy to maximize reproductive efficiency. This chapter synthesizes the current understanding of the physiology and pathophysiology of human parturition from the perspective of the evolutionary biology and comparative physiology of birth timing. We examine selective pressures that may have influenced parturition physiology and pathophysiology; the principal organ for parturition, the uterus, and its functional tissue types: the myometrium, cervix, and decidua; and the hormonal interactions that control their function to either sustain pregnancy or facilitate labor and delivery. Conserved uterotropic (causing uterine growth) and uterotonic (causing uterine contraction) hormonal pathways are present across viviparous species, although their regulatory patterns and sites of production differ. An emerging theme is that parturition involves positive-feedback loops leading to intrauterine inflammation, enhanced uterine contractility, membrane rupture, and cervical dilation, functioning at a paracrine level within each of the gestational tissues and in an endocrine fashion between the uterus and extrauterine sites.
Associations between developmental trajectories of movement variety and visual attention in fullterm and preterm infants during the first six months postterm
2015, Early Human Development
During early infancy major developmental changes, both in the variety of body movements and in visual attention, help the infant to explore its surroundings. Both behaviours depend on a gradual shift from subcortical to cortical functioning.
First, to determine whether preterms reach mature levels of movement variety (the number of different movement patterns) and visual attention earlier than fullterms. Second, to determine whether individual developmental trajectories of movement variety and visual attention were associated. Finally, we compared the associations of developmental trajectories between fullterm and preterm infants.
In this longitudinal study, 20 fullterm and 9 low-risk preterm infants performed a visual disengagement task every four weeks from six weeks until six months postterm. For each infant we drew up developmental trajectories for movement variety, and for frequencies and latencies of looks. We analyzed the developmental trajectories by means of general linear model (GLM) repeated measures and Monte Carlo analyses.
In comparison to fullterms, preterm infants showed a similar increase in movement variety over time (F(4,108) = 0.27; partial eta² = 0.01; P = .90). Visual attention reached mature levels four weeks earlier than movement variety. This effect was stronger in fullterm infants. Neither in fullterm nor in preterm infants did we find an association between the developmental trajectories of movement variety and visual attention. P values ranged from .37 to .99.
During the first 6 months postterm, movement variety and visual attention developed independently. Temporarily, preterm exposure to the extrauterine environment led to shorter latencies of looks but it did not affect developmental trajectories of frequencies of looks and movement variety.
Evaluation of therapeutic effect and cytokine change during transplacental Digoxin treatment for fetal heart failure associated with fetal tachycardia, a case-control study
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Maternal stress in pregnancy: Considerations for fetal development
2012, Journal of Adolescent Health
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We wonder whether the conceptualization of maternal stress originally as a developmental teratogen, and subsequently within a programming framework originally used to examine the role of prenatal undernutrition on adult metabolic disorders [87], may have canalized research toward a search for adverse outcomes in lieu of a broader perspective on the interplay between the maternal environment and the developing fetal brain. There is long-standing theoretical and empirical support for an inverted U-shaped association between stress and performance, as described by Yerkes and Dodson more than a century ago [88], consistent with the current view that the human brain requires sufficient, but not overwhelming, stress to promote optimal neural development both before [89] and after birth [90]. This perspective is consistent with the model of the role of early postnatal stress in the promotion of developmental adaptation as reflected by arousal regulation and resilience stress in nonhuman primates [91].
There is significant current interest in the degree to which prenatal exposures, including maternal psychological factors, influence child outcomes. Studies that detect an association between prenatal maternal psychological distress and child developmental outcomes are subject to a number of interpretative challenges in the inference of causality. Some of these are common to many types of prenatal exposures that must necessarily rely on observational designs. Such challenges include the correlation between prenatal and postnatal exposures and the potential role of other sources of shared influence, such as genetic factors. Others are more specific to this area of research. These include confounding between maternal report of child outcomes and the maternal psychological attributes under study, difficulties in distinguishing maternal stress from more ubiquitous aspects of maternal personality, and the lack of association between cortisol and measures of maternal psychological stress. This article considers these methodological issues and offers an additional methodology focused on fetal neurobehavior for discerning potential mechanisms that may mediate associations between maternal psychological functioning and the developing fetal nervous system.

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Fetal adaptation to stress: Part I: acceleration of fetal maturation and earlier birth triggered by placental insufficiency in humans

Abstract

Introduction

Section snippets

Possible fetal adaptation to unfavorable circumstances

Neurological assessment of maturation: methodological issues

Are adaptive changes observed in the lung ?

Natural history in pregnancy induced hypertension

Conclusion

Am. J. Obstet. Gynecol.

Am. J. Obstet. Gynecol.

Am. J. Obstet. Gynecol.

Brain Dev.

Am. J. Obstet. Gynecol.

Neurochem. Int.

Early Hum. Dev.

Am. J. Obstet. Gynecol.

Pediatr. Neurol.

Early Hum. Dev.

J. Pediatr.

J. Pediatr.

Am. J. Obstet. Gynecol.

Am. J. Obstet. Gynecol.

Am. J. Obstet. Gynecol.

J. Pediatr.

Am. J. Obstet. Gynecol.

Am. J. Obstet. Gynecol.

Am. J. Obstet. Gynecol.

Eur. J. Obstet. Gynecol. Reprod. Biol.

Am. J. Obstet. Gynecol.

Am. J. Obstet. Gynecol.

Am. J. Obstet. Gynecol.

Lancet

Br. J. Obstet. Gynecol.

Fetal brain and pulmonary adaptation in multiple pregnancy

When is it best to be born? A pediatric perspective on behalf of the fetus

Intrauterine growth retardation: adaptation of pathology

Pediatrics