The Patent Ductus Arteriosus in Extremely Preterm Neonates Is More than a Hemodynamic Challenge: New Molecular Insights

Sellmer, Anna; Henriksen, Tine Brink; Palmfeldt, Johan; Bech, Bodil Hammer; Astono, Julie; Bennike, Tue Bjerg; Hjortdal, Vibeke E.

doi:10.3390/biom12091179

Cited by 5 publications

(4 citation statements)

References 70 publications

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“…As well as having specific immunoregulatory roles, in the neonatal setting or relevant animal models, these proteins are associated with several comorbidities and developmental consequences of preterm birth. These include lung development and disease such as BPD [ 63 – 75 ], in utero and postnatal growth failure [ 76 – 79 ], HCA [ 7 , 80 , 81 ], patent ductus arteriosus [ 82 – 85 ], retinopathy of prematurity [ 86 – 90 ], NEC [ 91 – 93 ], hyperglycaemia [ 94 ], sepsis [ 93 , 95 – 98 ], brain injury [ 32 , 99 – 102 ], and neurodevelopmental outcomes [ 103 – 107 ].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic scores derived in saliva are associated with gestational age at birth

Mckinnon,

Conole,

Vaher

et al. 2024

Clin Epigenet

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Background Epigenetic scores (EpiScores), reflecting DNA methylation (DNAm)-based surrogates for complex traits, have been developed for multiple circulating proteins. EpiScores for pro-inflammatory proteins, such as C-reactive protein (DNAm CRP), are associated with brain health and cognition in adults and with inflammatory comorbidities of preterm birth in neonates. Social disadvantage can become embedded in child development through inflammation, and deprivation is overrepresented in preterm infants. We tested the hypotheses that preterm birth and socioeconomic status (SES) are associated with alterations in a set of EpiScores enriched for inflammation-associated proteins. Results In total, 104 protein EpiScores were derived from saliva samples of 332 neonates born at gestational age (GA) 22.14 to 42.14 weeks. Saliva sampling was between 36.57 and 47.14 weeks. Forty-three (41%) EpiScores were associated with low GA at birth (standardised estimates |0.14 to 0.88|, Bonferroni-adjusted p-value < 8.3 × 10−3). These included EpiScores for chemokines, growth factors, proteins involved in neurogenesis and vascular development, cell membrane proteins and receptors, and other immune proteins. Three EpiScores were associated with SES, or the interaction between birth GA and SES: afamin, intercellular adhesion molecule 5, and hepatocyte growth factor-like protein (standardised estimates |0.06 to 0.13|, Bonferroni-adjusted p-value < 8.3 × 10−3). In a preterm subgroup (n = 217, median [range] GA 29.29 weeks [22.14 to 33.0 weeks]), SES–EpiScore associations did not remain statistically significant after adjustment for sepsis, bronchopulmonary dysplasia, necrotising enterocolitis, and histological chorioamnionitis. Conclusions Low birth GA is substantially associated with a set of EpiScores. The set was enriched for inflammatory proteins, providing new insights into immune dysregulation in preterm infants. SES had fewer associations with EpiScores; these tended to have small effect sizes and were not statistically significant after adjusting for inflammatory comorbidities. This suggests that inflammation is unlikely to be the primary axis through which SES becomes embedded in the development of preterm infants in the neonatal period. Graphical abstract

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Section: Discussionmentioning

confidence: 99%

Epigenetic scores derived in saliva are associated with gestational age at birth

Mckinnon,

Conole,

Vaher

et al. 2024

Clin Epigenet

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“…There is very little research on the relationship between IL-1 and PDA. However, echocardiography and plasma samples taken on day 3 of life in 53 infants, with a GA at birth below 28 completed weeks, revealed an association between large PDA (>1.5 mm) and increased pro-inflammatory (IL-1β, IL-8) and anti-inflammatory (IL-1Ra, IL-10) cytokines ( 125 ).…”

Section: Neonatal Outcomesmentioning

confidence: 99%

The role of interleukin-1 in perinatal inflammation and its impact on transitional circulation

Owen

Garrick²,

Peterson³

et al. 2023

Front. Pediatr.

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Preterm birth is defined as delivery at <37 weeks of gestational age (GA) and exposes 15 million infants worldwide to serious early life diseases. Lowering the age of viability to 22 weeks GA entailed provision of intensive care to a greater number of extremely premature infants. Moreover, improved survival, especially at extremes of prematurity, comes with a rising incidence of early life diseases with short- and long-term sequelae. The transition from fetal to neonatal circulation is a substantial and complex physiologic adaptation, which normally happens rapidly and in an orderly sequence. Maternal chorioamnionitis or fetal growth restriction (FGR) are two common causes of preterm birth that are associated with impaired circulatory transition. Among many cytokines contributing to the pathogenesis of chorioamnionitis-related perinatal inflammatory diseases, the potent pro-inflammatory interleukin (IL)-1 has been shown to play a central role. The effects of utero-placental insufficiency-related FGR and in-utero hypoxia may also be mediated, in part, via the inflammatory cascade. In preclinical studies, blocking such inflammation, early and effectively, holds great promise for improving the transition of circulation. In this mini-review, we outline the mechanistic pathways leading to abnormalities in transitional circulation in chorioamnionitis and FGR. In addition, we explore the therapeutic potential of targeting IL-1 and its influence on perinatal transition in the context of chorioamnionitis and FGR.

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“…As well as having specific immunoregulatory roles, in the neonatal setting or relevant animal models, these proteins are associated with several comorbidities and developmental consequences of preterm birth. These include lung development and disease such as BPD [55][56][57][58][59][60][61][62][63][64][65][66][67], in utero and postnatal growth failure [68][69][70][71], HCA [7,72,73], patent ductus arteriosus [74][75][76][77], retinopathy of prematurity [78][79][80][81][82], NEC [83][84][85], hyperglycaemia [86], sepsis [85,[87][88][89][90], brain injury [32,[91][92][93][94], and neurodevelopmental outcomes [95][96][97][98]…”

Section: Associations Between Birth Ga and Episcoresmentioning

confidence: 99%

Epigenetic scores indicate differences in the proteome of preterm infants

Mckinnon,

Conole,

Vaher

et al. 2023

Preprint

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BackgroundEpigenetic scores (EpiScores), reflecting DNA methylation (DNAm)-based surrogates for complex traits, have been developed for multiple circulating proteins. EpiScores for pro-inflammatory proteins, such as C-reactive protein (DNAm CRP), are associated with brain health and cognition in adults and with inflammatory comorbidities of preterm birth in neonates. Social disadvantage can become embedded in child development through inflammation, and deprivation is over-represented in preterm infants. We tested the hypotheses that preterm birth and socioeconomic status (SES) are associated with alterations in a set of EpiScores enriched for inflammation-associated proteins.Results104 protein EpiScores were derived from saliva samples of 332 neonates born at gestational age (GA) 22.14 to 42.14 weeks. Saliva sampling was between 36.57 and 47.14 weeks. Forty-three (41%) EpiScores were associated with low GA at birth (standardised estimates |0.14 to 0.88|, Bonferroni-adjustedp-value <8.3×10−3). These included EpiScores for chemokines, growth factors, proteins involved in neurogenesis and vascular development, cell membrane proteins and receptors, and other immune proteins. Three EpiScores were associated with SES, or the interaction between birth GA and SES: afamin, intercellular adhesion molecule 5 and hepatocyte growth factor-like protein (standardised estimates |0.06 to 0.13|, Bonferroni-adjustedp-value <8.3×10−3). In a preterm sub-group (n=217, median [range] GA 29.29 weeks [22.14 to 33.0 weeks]), SES-EpiScore associations did not remain statistically significant after adjustment for sepsis, bronchopulmonary dysplasia, necrotising enterocolitis, and histological chorioamnionitis.ConclusionsLow birth GA is substantially associated with a set of EpiScores. The set was enriched for inflammatory proteins, providing new insights into immune dysregulation in preterm infants. SES had fewer associations with EpiScores; these tended to have small effect sizes and were not statistically significant after adjusting for inflammatory comorbidities. This suggests that inflammation is unlikely to be the primary axis through which SES becomes embedded in the development of preterm infants in the neonatal period.

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The Patent Ductus Arteriosus in Extremely Preterm Neonates Is More than a Hemodynamic Challenge: New Molecular Insights

Cited by 5 publications

References 70 publications

Epigenetic scores derived in saliva are associated with gestational age at birth

Epigenetic scores derived in saliva are associated with gestational age at birth

The role of interleukin-1 in perinatal inflammation and its impact on transitional circulation

Epigenetic scores indicate differences in the proteome of preterm infants

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