Elsevier

Psychoneuroendocrinology

Volume 106, August 2019, Pages 20-27
Psychoneuroendocrinology

The transgenerational transmission of maternal adverse childhood experiences (ACEs): Insights from placental aging and infant autonomic nervous system reactivity

https://doi.org/10.1016/j.psyneuen.2019.03.022Get rights and content

Highlights

  • High maternal ACE exposure predicted shorter placental TL.

  • Placental TL moderated the relation between maternal ACE and infant RSA.

  • Infant health may be influenced by maternal preconception adversity.

  • Maternal ACE-related infant ANS differences are influenced by placental aging.

Abstract

Objective

To test alterations in placental cellular aging as one pathway by which maternal early adversity influences physiologic development in her offspring.

Methods

Maternal report of her adverse childhood experiences (ACE) was obtained prenatally along with measures of prenatal stress and demographic information. Placentas (N = 67) were collected at birth and telomere length (TL) was measured in four separate fetally-derived placental tissues: amnion, chorion, villus, and umbilical cord. At four months of age, infants completed the still-face paradigm (SFP) during which respiratory sinus arrhythmia (RSA) data were collected; RSA reactivity and RSA recovery was available from 44 and 41 infants respectively. Multi-level mixed effects models examined the impact of maternal ACE score on placental TL. Generalized linear models tested the relation between composite placental TL and infant RSA, as well as the moderation of maternal ACE score and infant RSA by composite placental TL.

Results

Higher maternal ACE score significantly predicted shorter placental TL across tissues (β = −0.015; P = 0.036) and infant RSA across the SFP. No direct relation was found between placental TL and RSA, however composite placental TL moderated the relation between ACE score and both infant RSA reactivity (β = 0.025; P = 0.005) and RSA recovery (β = −0.028; P = 0.032). In infants with shorter composite placental TL, higher ACE score predicted greater RSA suppression during the still-face epoch relative to play period 1 and greater RSA augmentation during play period 2 relative to the still-face epoch.

Conclusions

These data are the first, to our knowledge, to report that changes in placental TL influence the transgenerational impact of maternal early life adversity on the development of her offspring’s autonomic nervous system.

Introduction

Although the impact of maternal prenatal stress on her offspring is established, recent data suggests that the influence of maternal adversity on her offspring is better conceptualized from a life-course perspective that includes a mother’s own childhood experiences (Gray et al., 2017; McDonnell and Valentino, 2016; Moog et al., 2016). Within an individual, adverse childhood experiences (ACEs) are hypothesized to contribute to the earlier onset of both mental and physical illness through accelerated aging (Danese and McEwen, 2012; Drury et al., 2012; Felitti et al., 1998; Ridout et al., 2017). Both elevated cellular stress, indexed by measurements of oxidative stress and telomere length (TL), and reduced parasympathetic regulation of cardiac function indexed by respiratory sinus arrhythmia (RSA), are pathways predicted to contribute to the health risks associated with early life adversity (Danese and McEwen, 2012; Demissie et al., 2006; Fitzpatrick et al., 2006; Haycock et al., 2014; Masi et al., 2007; Ridout et al., 2017). TL, RSA, and the cardiovascular responses to stressors are also hallmarks of the aging process (Masi et al., 2007; Stratton et al., 2003). Given their mechanistic role in linking adversity to health outcomes within an individual, determining if these biological outcomes contribute to transgenerational effects is warranted.

The Developmental Origins of Health and Disease (DoHaD) model proposes that the origins of health and disease are found in the perinatal period (Barker, 1990; Barker and Thornburg, 2013). Alterations in developing stress response systems, such as the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal axis (HPA), are hypothesized pathways by which the earliest of experiences drive future health trajectories. Respiratory sinus arrhythmia (RSA) is one index of the ANS stress response system that is sensitive to prenatal stress exposure and preconception adversity (i.e., ACE exposure) in the next generation (DiPietro et al., 2006; Gray et al., 2017). RSA is the natural beat-to-beat variation in heart rate, in synchrony with respiration, which indexes parasympathetic regulation of cardiac function (Grossman and Taylor, 2007). Dynamic changes in RSA across a stress paradigm reflect an individual’s ability both to mobilize biological resources in response to a challenge and to return to a regulated state after the stressor is addressed. Development of RSA stress responsivity profiles, including both reactivity and recovery, begins in utero (Monk et al., 2000). Therefore, changes to the intrauterine environment, as a consequence of maternal life-course experiences, have the potential to impact the developmental trajectory of RSA profiles. Previously, we reported that maternal ACE exposure influences infant RSA independent of prenatal stress (Gray et al., 2017). However, to date, what aspects of the fetal environment contribute to these changes to the next generation is unclear.

Transgenerational transmission of maternal preconception adversity is hypothesized to occur via alterations in multiple factors across development including epigenetic changes in the germline, alterations to the intrauterine environment, and differences in postnatal caregiving, or, more likely some combination of these factors (Bale, 2015). When contemplating transgenerational effects, it is notable that maternal ACE exposure is associated with both pregnancy complications and preterm birth, highlighting the influence of the intrauterine environment as a target for ACE-related impacts (Cammack et al., 2011; Christiaens et al., 2015; Smith et al., 2016). A key organ at the maternal-fetal interface linked to pregnancy complications and preterm birth with the potential to transmit transgenerational effects is the placenta (Biron-Shental et al., 2010a, b; Moog et al., 2016; Waldorf and McAdams, 2013). Biological indicators of compromised placental function include hypoxia and elevated oxidative stress, two factors indexed by telomere length (TL) (Biron-Shental et al., 2010b; Jauniaux et al., 2006; Polenttini et al., 2015a). Further, placental TL shortening is etiologically related to the onset of labor and parturition, as well as certain pregnancy complications, suggesting broader implications for placental TL (Biron-Shental et al., 2010a,b; Menon et al., 2016; Phillippe, 2014; Phillippe, 2015). To date, however, no studies have examined placental TL in relation to maternal ACE exposure.

To explore the role of the placenta in the transmission of maternal adversity across generations, this study examined changes in placental TL as a moderator of the relation between maternal ACE and infant RSA. Identification of the earliest developmental time-points when the transgenerational effects of maternal life-course adversity are recognizable provides unique opportunities for mitigation strategies designed to combat the recalcitrant risk associated with maternal adversity.

Section snippets

Population

Recruitment of pregnant mothers took place at prenatal clinics, WIC (Women, infants, and children) clinics, and other ongoing studies at any point during their pregnancy as part of a prospective study of the impact of maternal life course stress on infant development. Mothers were at least 18 years of age, carrying a singleton pregnancy, and English speaking. Sixty-seven placentas were collected as placental collection began later in the course of the parent grant due to the receipt of

Demographics

Sixty-seven placentas yielded a total of 268 samples for TL measurement across placental tissue types. Descriptive outcomes of the sample demographics are listed in Table 1. A majority of mothers were Black (Table 1; 56.7%) and were approximately 28 years of age at conception. Mothers reported a mean ACE score of 2.31 ± 2.32 and mean PNMS score of 1.33 ± 1.45. The gestational period averaged 39.02 ± 1.41 weeks and infants weighed on average 3.35 ± 0.60 kg at birth. There were more male infants

Discussion

This is the first study to demonstrate the impact of maternal ACE exposure on TL, a marker of cellular stress, in the placenta, an effect that was robust to the inclusion of covariates. Beyond this we demonstrate that composite placental TL moderated the link between maternal ACE and later infant autonomic development, providing the first evidence of a physiologic consequence of accelerated placental aging in infants.

In our study of mostly term infants, we demonstrate that both maternal ACE

Conclusion

Recent literature continues to bolster the observed negative impacts of ACE exposure across health outcomes and across generations. Our data suggests that shorter placental TL is one molecular pathway by which ACEs may influence health across generations. Even after considering perinatal outcomes, infants born to mothers with high ACE scores remain at risk, likely carrying undetected advancements in their stress response systems, similar to the accelerated amygdala-prefrontal cortex coupling

Conflict of interest

The authors report no conflict of interest.

Source of funding

This study was funded by the National Institutes of Health [1R01MH101533-01, 3R01MH101533-02S3 {SD}], the Tulane University Oliver Fund (SD), and the Eunice Kennedy Shriver National Institute of Child Health & Human Development [K12HD043451 {SD & SG} & L30HD085275 {SG}]. The funding sources had no direct involvement in the study or manuscript preparation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.

Acknowledgements

The authors would like to thank the mothers and their infants who participated in the study and all of the staff and students who assisted in the recruitment of participants, conducting laboratory visits, collection of psychophysiological data, DNA extractions, and many other aspects of the study.

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