Placental programming, perinatal inflammation, and neurodevelopment impairment among those born extremely preterm

Bangma, Jacqueline T.; Hartwell, Hadley J.; Santos, Hudson P.; Fry, Rebecca C.

doi:10.1038/s41390-020-01236-1

Cited by 34 publications

(24 citation statements)

References 191 publications

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“…Socioeconomic factors play an important role in maternal health, access to prenatal care, rates of preterm birth, and infant morbidity and mortality outside of the NICU 4,5,31 . While in the NICU, preterm infants have standardized care guidelines that might be expected to limit the impact of socioeconomic deprivation on adverse outcomes.…”

Section: Discussionmentioning

confidence: 99%

Neighborhood deprivation is associated with NICU mortality for extremely premature infants: A 4-NICU study

Sullivan

Doshi

Chernyavskiy

et al. 2022

Preprint

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Importance: Socioeconomic status impacts pregnancy outcomes and child development after NICU discharge for infants born prematurely, but has not been well studied for outcomes during the NICU stay. The Area Deprivation Index (ADI) is a validated measure of neighborhood disadvantage that uses Census data on income, education, employment, and housing quality. Objective: In NICUs in different US regions, determine if ADI predicts NICU mortality and morbidity in extremely premature infants. Design: We conducted a retrospective cohort study. Setting: Four level IV neonatal intensive care units (NICU) in different US geographic regions: Northeast, Mid-Atlantic, Midwest, and South. Participants: Non-Hispanic White and Black extremely premature infants (gestational age <29 weeks) and admitted to a study NICU from 2012-2020. Exposures: ADI, race, BW, sex, and outborn status (admitted after transfer from an outside birth hospital). Main Outcomes and Measures: We converted addresses to census blocks, identified by 12-digit Federal Information Processing Series (FIPS) codes, to link residences to the national ADI percentile of study participants. We analyzed the relationship between ADI and NICU mortality using Bayesian logistic regression adjusted for race, BW, outborn status, and sex. Predictors were considered significant if the 95% Credible Intervals excluded zero. We also analyzed the effect of ADI on NICU morbidities of late-onset sepsis, necrotizing enterocolitis, and severe intraventricular hemorrhage. Results: We studied 2,765 infants. In univariate analysis, infants with higher ADI were more likely to be Black, suffer from short-term morbidities, and die before NICU discharge. ADI did not correlate with BW (r = -0.05) or sex. Black infants also had higher mortality and lower BW. In a multivariable model, lower BW, higher ADI, and male sex were statistically significant risk factors, while Black race and outborn status were not. Using these methods, ADI was also identified as a risk factor for NICU morbidities. Conclusions and Relevance: Among extremely preterm infants admitted to four NICUs in different US geographic regions, ADI was a risk factor for mortality and morbidity after adjusting for multiple covariates. These findings have implications for public health measures to improve prenatal and NICU care for patients from disadvantaged areas.

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Section: Discussionmentioning

confidence: 99%

Neighborhood deprivation is associated with NICU mortality for extremely premature infants: A 4-NICU study

Sullivan

Doshi

Chernyavskiy

et al. 2022

Preprint

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“…Another epigenetic effect of high free fatty acid in the offspring of women with obesity is the silencing of homeobox gene Pdx-1 which increased islet cell apoptosis and worsens the failing hyperplastic islet cells in newborn observed in women with obesity, setting the stage for early pancreatic exhaustion and type 2 diabetes in the offspring of women that were obese during pregnancy ( 68 ). Based on Extremely Low Gestational Age Newborn Study (ELGAN study), inflammation and abnormal placental transport are two mechanisms of epigenetic programming associated with maternal obesity that increase the risk for poor outcomes ( 112 ). As summarized for the biome, the literature on the role of epigenetics in adverse outcomes in offspring of women with obesity during pregnancy is sparse; therefore, there is a need for more research in this field.…”

Section: Pathogenesis Of Cardiopulmonary Effects In the Offspring Of ...mentioning

confidence: 99%

The Epidemiology and Mechanisms of Lifetime Cardiopulmonary Morbidities Associated With Pre-Pregnancy Obesity and Excessive Gestational Weight Gain

Rastogi

2022

Front. Cardiovasc. Med.

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Obesity has reached pandemic proportions in the last few decades. The global increase in obesity has contributed to an increase in the number of pregnant women with pre-pregnancy obesity or with excessive gestational weight gain. Obesity during pregnancy is associated with higher incidence of maternal co-morbidities such as gestational diabetes and hypertension. Both obesity during pregnancy and its associated complications are not only associated with immediate adverse outcomes for the mother and their newborns during the perinatal period but, more importantly, are linked with long-term morbidities in the offsprings. Neonates born to women with obesity are at higher risk for cardiac complications including cardiac malformations, and non-structural cardiac issues such as changes in the microvasculature, e.g., elevated systolic blood pressure, and overt systemic hypertension. Pulmonary diseases associated with maternal obesity include respiratory distress syndrome, asthma during childhood and adolescence, and adulthood diseases, such as chronic obstructive pulmonary disease. Sequelae of short-term complications compound long-term outcomes such as long-term obesity, hypertension later in life, and metabolic complications including insulin resistance and dyslipidemia. Multiple mechanisms have been proposed to explain these adverse outcomes and are related to the emerging knowledge of pathophysiology of obesity in adults. The best investigated ones include the role of obesity-mediated metabolic alterations and systemic inflammation. There is emerging evidence linking metabolic and immune derangements to altered biome, and alteration in epigenetics as one of the intermediary mechanisms underlying the adverse outcomes. These are initiated as part of fetal adaptation to obesity during pregnancy which are compounded by rapid weight gain during infancy and early childhood, a known complication of obesity during pregnancy. This newer evidence points toward the role of specific nutrients and changes in biome that may potentially modify the adverse outcomes observed in the offsprings of women with obesity.

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“…As discussed in detail for the lung, both IUGR ( 299 ) and maternal obesity-associated ( 300 ) models seem to induce inflammation in other organs as well. Briefly summarized, it is demonstrated that neuroinflammation is an important mechanism contributing to neurocognitive impairment after IUGR and maternal obesity ( 301 , 302 ) and the window of vulnerability extends well-beyond birth ( 303 , 304 ). Circulating inflammatory proteins were even tested as biomarkers for later cognitive impairment in preterm infants ( 305 ).…”

Section: Systemic Consequences Of Fetal Programmingmentioning

confidence: 99%

Perinatal Nutritional and Metabolic Pathways: Early Origins of Chronic Lung Diseases

et al. 2021

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Lung development is not completed at birth, but expands beyond infancy, rendering the lung highly susceptible to injury. Exposure to various influences during a critical window of organ growth can interfere with the finely-tuned process of development and induce pathological processes with aberrant alveolarization and long-term structural and functional sequelae. This concept of developmental origins of chronic disease has been coined as perinatal programming. Some adverse perinatal factors, including prematurity along with respiratory support, are well-recognized to induce bronchopulmonary dysplasia (BPD), a neonatal chronic lung disease that is characterized by arrest of alveolar and microvascular formation as well as lung matrix remodeling. While the pathogenesis of various experimental models focus on oxygen toxicity, mechanical ventilation and inflammation, the role of nutrition before and after birth remain poorly investigated. There is accumulating clinical and experimental evidence that intrauterine growth restriction (IUGR) as a consequence of limited nutritive supply due to placental insufficiency or maternal malnutrition is a major risk factor for BPD and impaired lung function later in life. In contrast, a surplus of nutrition with perinatal maternal obesity, accelerated postnatal weight gain and early childhood obesity is associated with wheezing and adverse clinical course of chronic lung diseases, such as asthma. While the link between perinatal nutrition and lung health has been described, the underlying mechanisms remain poorly understood. There are initial data showing that inflammatory and nutrient sensing processes are involved in programming of alveolarization, pulmonary angiogenesis, and composition of extracellular matrix. Here, we provide a comprehensive overview of the current knowledge regarding the impact of perinatal metabolism and nutrition on the lung and beyond the cardiopulmonary system as well as possible mechanisms determining the individual susceptibility to CLD early in life. We aim to emphasize the importance of unraveling the mechanisms of perinatal metabolic programming to develop novel preventive and therapeutic avenues.

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Placental programming, perinatal inflammation, and neurodevelopment impairment among those born extremely preterm

Cited by 34 publications

References 191 publications

Neighborhood deprivation is associated with NICU mortality for extremely premature infants: A 4-NICU study

Neighborhood deprivation is associated with NICU mortality for extremely premature infants: A 4-NICU study

The Epidemiology and Mechanisms of Lifetime Cardiopulmonary Morbidities Associated With Pre-Pregnancy Obesity and Excessive Gestational Weight Gain

Perinatal Nutritional and Metabolic Pathways: Early Origins of Chronic Lung Diseases

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