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Prematurity, Preterm-Born Adults, and Long-Term Effects on Children and Adults

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A special issue of Children (ISSN 2227-9067).

Deadline for manuscript submissions: closed (25 July 2022) | Viewed by 33447

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Special Issue Editor

Prof. Dr. Vasanth H.S. Kumar

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Guest Editor

Department of Pediatrics, University at Buffalo, Buffalo, NY 14203, USA
Interests: BPD and hyperoxic lung injury; pulmonary hypertension; resuscitation; long-term effects of prematurity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Advances in neonatal care have led to improved survival of premature infants with a concurrent increase in the incidence of preterm birth across the world. The spectrum of preterm infants extending from extremes of gestational age to the late preterm infant is at higher risk of adverse short-term and long-term outcomes. Some of these problems may not show up for considerable periods, even into adulthood. Management of short-term outcomes such as bronchopulmonary dysplasia (BPD) and necrotizing enterocolitis (NEC) is further challenged by a broad spectrum of related long-term morbidities and neurodevelopmental issues in these infants.

Adults born preterm are at higher risk of neurobehavioral and adult-onset morbidities compared to term infants. The Special Issue will address problems relating to prematurity as infants grow into adults. Cardiorespiratory morbidity such as BPD, asthma, lung function, and pulmonary hypertension, organ-specific health issues (poor feeding, gastrointestinal, metabolic, and renal morbidities), or outcomes relating to neurodevelopment are of interest. Caffeine, oxygen, nutrition, and other factors that influence the growth and development of preterm infants are considered. Newer strategies, including machine learning and unique approaches such as bridging pediatric and adult programs to address research gaps in longitudinal assessment and management of premature infants, contributing to improved survival and long-term outcomes as they grow into adults, are of interest.

We welcome articles from across the globe on all matters relating to prematurity and long-term health to better the lives of these infants. Both reviews and original research will be considered for publication. The authors are welcome to contact the editor directly at [email protected] for questions or clarifications.

Prof. Vasanth H.S. Kumar
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Children is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Bronchopulmonary dysplasia
Hyperoxia
Prematurity
Caffeine
Asthma
Adults born preterm
Growth
Neurodevelopment

Published Papers (10 papers)

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Editorial

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3 pages, 166 KiB

Open AccessEditorial

Special Issue: Prematurity, Preterm-Born Adults, and Long-Term Effects on Children and Adults

by Vasantha H. S. Kumar

Children 2023, 10(6), 989; https://doi.org/10.3390/children10060989 - 31 May 2023

Viewed by 819

Abstract

The incidence of preterm births is increasing globally, with increasing survival into adulthood [...] Full article

(This article belongs to the Special Issue Prematurity, Preterm-Born Adults, and Long-Term Effects on Children and Adults)

Research

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10 pages, 342 KiB

Open AccessArticle

Motor Performance in Association with Perceived Loneliness and Social Competence in 11-Year-Old Children Born Very Preterm

by Minttu Helin, Max Karukivi, Leena Haataja, Päivi Rautava, Niina Junttila, Susanna Salomäki, Liisa Lehtonen and Sirkku Setänen

Children 2022, 9(5), 660; https://doi.org/10.3390/children9050660 - 4 May 2022

Cited by 4 | Viewed by 1641

Abstract

Background: Very preterm birth may affect motor performance and social competence up to adulthood. Our objective was to describe perceived loneliness and social competence in children born very preterm in relation to motor impairment. Methods: 165 children born very preterm (birth weight ≤ 1500 g and/or gestational age < 32 weeks) were assessed at 11 years of age. Cerebral palsy (CP) was diagnosed by 2 years of age. At 11 years of age, motor outcome was assessed using the Movement Assessment Battery for Children—Second edition (Movement ABC-2). Loneliness was evaluated by using the Peer Network and Dyadic Loneliness scale and social competence by using the Multisource Assessment of Children’s Social Competence Scale. Results: In total, 6 (4%) children had CP, 18 (11%) had Developmental Coordination Disorder (DCD) (Movement ABC-2 ≤ 5th percentiles), and 141 (85%) had typical motor development. There was no correlation between percentiles for total scores of the Movement ABC-2 and perceived loneliness or social competence when the children with motor impairment (CP or DCD) were excluded. Children with DCD reported less perceived loneliness, but more problems with social competence compared to children with CP. Conclusions: It is important to recognize children born very preterm with DCD to provide interventions and support services to prevent social exclusion. Full article

(This article belongs to the Special Issue Prematurity, Preterm-Born Adults, and Long-Term Effects on Children and Adults)

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10 pages, 648 KiB

Open AccessEditor’s ChoiceArticle

Anterior Chamber Angle in Adults Born Extremely, Very, and Moderately Preterm with and without Retinopathy of Prematurity—Results of the Gutenberg Prematurity Eye Study

by Achim Fieß, Sandra Gißler, Eva Mildenberger, Michael S. Urschitz, Agnes Fauer, Heike M. Elflein, Fred Zepp, Bernhard Stoffelns, Norbert Pfeiffer and Alexander K. Schuster

Children 2022, 9(2), 281; https://doi.org/10.3390/children9020281 - 18 Feb 2022

Cited by 16 | Viewed by 1896

Abstract

Purpose: To determine whether prematurity and associated factors affect the anterior chamber angle (ACA) width in adulthood. Methods: The Gutenberg Prematurity Eye Study (GPES) is a retrospective cohort study with a prospective ophthalmologic examination of adults (age 18–52 years) in Germany. All participants were examined with Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany) using linear regression analysis to assess the associations of ACA in the different sectors with gestational age (GA), birth weight, birth weight percentile, retinopathy of prematurity (ROP), ROP treatment, placental insufficiency, preeclampsia, and breastfeeding. Results: In total, 516 eyes of 319 preterm and full-term individuals (aged 28.9 ± 8.8 years, 188 females) were examined. ROP treatment was associated with smaller ACA width in the nasal (B = −9.6 [95%CI: −14.7; −4.5] degree; p < 0.001) and temporal positions (B = −11.5 [95%CI: −17.7; −5.3] degree; p = 0.001), whereas non-treated individuals with ROP had an unaltered ACA width, as did individuals with low gestational age without ROP. Conclusion: Advanced stages of ROP following treatment with laser- and cryocoagulation lead to a smaller ACA width until adulthood, and hence may increase the risk of angle closure in later life. Full article

(This article belongs to the Special Issue Prematurity, Preterm-Born Adults, and Long-Term Effects on Children and Adults)

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11 pages, 408 KiB

Open AccessArticle

Growth of Very Preterm Infants in a Low-Resourced Rural Setting after Affiliation with a Human Milk Bank

by Chia-Huei Chen, Hui-Ya Chiu, Szu-Chia Lee, Hung-Yang Chang, Jui-Hsing Chang, Yen-Ju Chen, Lin Kang, Shang-Po Shen and Yung-Chieh Lin

Children 2022, 9(1), 80; https://doi.org/10.3390/children9010080 - 5 Jan 2022

Cited by 4 | Viewed by 1921

Abstract

The extrauterine growth restriction (EUGR) of very preterm infants has been associated with long-term complications and neurodevelopmental problems. EUGR has been reported at higher rates in low resource settings. There is limited research investigating how metropolitan human milk banks contribute to the growth outcomes of very preterm infants cared in rural areas. The setting of this study is located at a rural county in Taiwan and affiliated with the Taiwan Southern Human Milk Bank. Donor human milk was provided through a novel supplemental system. A renewal nutritional protocol was initiated as a quality improvement project after the affiliated program. This study aimed to compare the clinical morbidities and growth outcome at term equivalent age (TEA) of preterm infants less than 33 weeks of gestational age before (Epoch-I, July 2015–June 2018, n = 40) and after the new implementation (Epoch-II, July 2018–December 2020, n = 42). The Epoch-II group significantly increased in bodyweight z-score at TEA ((−0.02 ± 1.00) versus Epoch-I group (−0.84 ± 1.08), p = 0.002). In multivariate regression models, the statistical difference between two epochs in bodyweight z-score changes from birth to TEA was still noted. Modern human milk banks may facilitate the nutritional protocol renewal in rural areas and improve the growth outcomes of very preterm infants cared for. Establishing more distribution sites of milk banks should be encouraged. Full article

(This article belongs to the Special Issue Prematurity, Preterm-Born Adults, and Long-Term Effects on Children and Adults)

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13 pages, 1967 KiB

Open AccessArticle

Association of Birth Weight with Central and Peripheral Corneal Thickness in Adulthood—Results from the Population-Based German Gutenberg Health Study

by Achim Fieß, Michael S. Urschitz, Susanne Marx-Groß, Markus Nagler, Philipp S. Wild, Thomas Münzel, Manfred E. Beutel, Karl J. Lackner, Norbert Pfeiffer and Alexander K. Schuster

Children 2021, 8(11), 1006; https://doi.org/10.3390/children8111006 - 4 Nov 2021

Cited by 9 | Viewed by 1636

Abstract

Purpose: Low birth weight (BW) is associated with altered ocular geometry such as a steeper corneal shape in adulthood. However, it is unclear whether low birth weight affects corneal thickness development in the center or periphery in adulthood which may contribute to ocular disease. The purpose of this study was to investigate corneal thickness in former low birth weight individuals in adulthood. Methods: The German Gutenberg Health Study is a prospective, population-based study in which every participant (age range 40–80 years) was measured with Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany). BW was collected by self-reports. The relationship between birth weight and corneal thickness at different locations were assessed. Linear regression models were carried out including uni- and multivariable analyses with adjustment for age, sex, mean corneal radius, and white-to-white distance. Main outcome measures were corneal thickness at the apex, at the pupil center, and at the corneal periphery. Results: Overall, 5657 participants were successfully measured (3019 females, aged 56.0 ± 10.3 years). In multivariable analyses a lower BW was associated with a thinner corneal thickness at the apex (B = 1.71 µm/500 g, p < 0.001) and at the pupil (B = 1.69 µm/500 g, p < 0.001). These effects diminished towards the corneal periphery resulting in no differences in the perilimbal regions. Conclusion: The present study provides evidence that lower birth weight goes along with corneal thickness alterations even into adult ages of 40 to 80 years. Thinner measurements of the cornea were particularly found in the corneal center and diminished in the periphery. This indicates that there may be fetal origins affecting corneal thickness development particularly in the corneal center. Full article

(This article belongs to the Special Issue Prematurity, Preterm-Born Adults, and Long-Term Effects on Children and Adults)

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10 pages, 3508 KiB

Open AccessArticle

A Novel Association between YKL-40, a Marker of Structural Lung Disease, and Short Telomere Length in 10-Year-Old Children with Bronchopulmonary Dysplasia

by Ewa Henckel, Anna James, Jon R Konradsen, Björn Nordlund, Malin Kjellberg, Eva Berggren-Broström, Gunilla Hedlin, Sofie Degerman and Kajsa Bohlin

Children 2021, 8(2), 80; https://doi.org/10.3390/children8020080 - 24 Jan 2021

Cited by 7 | Viewed by 2662

Abstract

Extremely preterm infants are born with immature lungs and are exposed to an inflammatory environment as a result of oxidative stress. This may lead to airway remodeling, cellular aging and the development of bronchopulmonary dysplasia (BPD). Reliable markers that predict the long-term consequences of BPD in infancy are still lacking. We analyzed two biomarkers of cellular aging and lung function, telomere length and YKL-40, respectively, at 10 years of age in children born preterm with a history of BPD (n = 29). For comparison, these markers were also evaluated in sex-and-age-matched children born at term with childhood asthma (n = 28). Relative telomere length (RTL) was measured in whole blood with qPCR and serum YKL-40 with ELISA, and both were studied in relation to gas exchange and the regional ventilation/perfusion ratio using three-dimensional V/Q-scintigraphy (single photon emission computer tomography, SPECT) in children with BPD. Higher levels of YKL-40 were associated with shorter leukocyte RTL (Pearson’s correlation: −0.55, p = 0.002), but were not associated with a lower degree of matching between ventilation and perfusion within the lung. Serum YKL-40 levels were significantly higher in children with BPD compared to children with asthma (17.7 vs. 13.2 ng/mL, p < 0.01). High levels of YKL-40 and short RTLs were associated to the need for ventilatory support more than 1 month in the neonatal period (p < 0.01). The link between enhanced telomere shortening in childhood and structural remodeling of the lung, as observed in children with former BPD but not in children with asthma at the age of 10 years, suggests altered lung development related to prematurity and early life inflammatory exposure. In conclusion, relative telomere length and YKL-40 may serve as biomarkers of altered lung development as a result of early-life inflammation in children with a history of prematurity. Full article

(This article belongs to the Special Issue Prematurity, Preterm-Born Adults, and Long-Term Effects on Children and Adults)

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11 pages, 602 KiB

Open AccessFeature PaperArticle

Comparison of Blood Pressure and Kidney Markers between Adolescent Former Preterm Infants and Term Controls

by Eveline Staub, Natalie Urfer-Maurer, Sakari Lemola, Lorenz Risch, Katrina S. Evers, Tatjana Welzel and Marc Pfister

Children 2020, 7(9), 141; https://doi.org/10.3390/children7090141 - 17 Sep 2020

Cited by 11 | Viewed by 3113

Abstract

Background: Preterm infants are at an increased risk of developing hypertension and chronic kidney disease later in life. No recommendations exist for blood pressure (BP) and renal follow up for these patients. Aim: To compare BP and serum and urinary kidney markers between preterm-born adolescents and term-born controls. Methods: BP measurements in 51 preterm-born (≤32 weeks gestational age) and 82 term-born adolescents at the age of 10–15 years were conducted. Stepwise regression analysis explored the association between BP and participant characteristics. Kidney markers measured in the serum and urine were creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and uromodulin. Kidney markers measured in the serum were cystatin C, beta-2 microglobulin, and beta trace protein. Results: Systolic BP was significantly higher in preterm boys compared with term boys, but not in girls, and low birth weight was associated with higher BP in boys. In the preterm group, maternal hypertension/preeclampsia and adolescent height were associated with higher systolic BP. Serum creatinine and NGAL were significantly higher in the preterm group. Conclusions: Our study confirms an inverse sex-dependant relationship between birth weight and BP at adolescent age. The higher serum creatinine and NGAL in the preterm group may indicate that premature birth affects kidney function in the long term. Full article

(This article belongs to the Special Issue Prematurity, Preterm-Born Adults, and Long-Term Effects on Children and Adults)

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Review

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16 pages, 2327 KiB

Open AccessReview

Feeding Problems and Long-Term Outcomes in Preterm Infants—A Systematic Approach to Evaluation and Management

by Ranjith Kamity, Prasanna K. Kapavarapu and Amit Chandel

Children 2021, 8(12), 1158; https://doi.org/10.3390/children8121158 - 8 Dec 2021

Cited by 17 | Viewed by 13510

Abstract

Preterm infants are known to have long-term healthcare needs. With advances in neonatal medical care, younger and more preterm infants are surviving, placing a subset of the general population at risk of long-term healthcare needs. Oral feeding problems in this population often play a substantial yet under-appreciated role. Oral feeding competency in preterm infants is deemed an essential requirement for hospital discharge. Despite achieving discharge readiness, feeding problems persist into childhood and can have a residual impact into adulthood. The early diagnosis and management of feeding problems are essential requisites to mitigate any potential long-term challenges in preterm-born adults. This review provides an overview of the physiology of swallowing and oral feeding skills, disruptions to oral feeding in preterm infants, the outcomes of preterm infants with feeding problems, and an algorithmic approach to the evaluation and management of neonatal feeding problems. Full article

(This article belongs to the Special Issue Prematurity, Preterm-Born Adults, and Long-Term Effects on Children and Adults)

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13 pages, 905 KiB

Open AccessReview

Predicting Long-Term Respiratory Outcomes in Premature Infants: Is It Time to Move beyond Bronchopulmonary Dysplasia?

by Deepak Jain, Alexander Feldman and Subhasri Sangam

Children 2020, 7(12), 283; https://doi.org/10.3390/children7120283 - 10 Dec 2020

Cited by 9 | Viewed by 2966

Abstract

Premature birth has been shown to be associated with adverse respiratory health in children and adults; children diagnosed with bronchopulmonary dysplasia (BPD) in infancy are at particularly high risk. Since its first description by Northway et al. about half a century ago, the definition of BPD has gone through several iterations reflecting the changes in the patient population, advancements in knowledge of lung development and injury, and improvements in perinatal care practices. One of the key benchmarks for optimally defining BPD has been the ability to predict long-term respiratory and health outcomes. This definition is needed by multiple stakeholders for hosts of reasons including: providing parents with some expectations for the future, to guide clinicians for developing longer term follow-up practices, to assist policy makers to allocate resources, and to support researchers involved in developing preventive or therapeutic strategies and designing studies with meaningful outcome measures. Long-term respiratory outcomes in preterm infants with BPD have shown variable results reflecting not only limitations of the current definition of BPD, but also potentially the impact of other prenatal, postnatal and childhood factors on the respiratory health. In this manuscript, we present an overview of the long-term respiratory outcomes in infants with BPD and discuss the role of other modifiable or non-modifiable factors affecting respiratory health in preterm infants. We will also discuss the limitations of using BPD as a predictor of respiratory morbidities and some of the recent advances in delineating the causes and severity of respiratory insufficiency in infants diagnosed with BPD. Full article

(This article belongs to the Special Issue Prematurity, Preterm-Born Adults, and Long-Term Effects on Children and Adults)

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Other

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9 pages, 371 KiB

Open AccessSystematic Review

Pseudorandom Noise Forced Oscillation Technique to Assess Lung Function in Prematurely Born Children

by Shannon Gunawardana, Christopher Harris and Anne Greenough

Children 2022, 9(8), 1267; https://doi.org/10.3390/children9081267 - 22 Aug 2022

Cited by 1 | Viewed by 1410

Abstract

The forced oscillation technique (FOT) is a non-volitional assessment that is used during tidal breathing. A variant of FOT uses a pseudorandom noise (PRN) signal which we postulated might have utility in assessing lung function in prematurely born children. We, therefore, undertook a systematic review to evaluate the evidence regarding PRN FOT. A comprehensive search of the literature was conducted by using the following databases: Medline, Embase, Web of Science and CINAHL. Observational studies, case series/reports and randomized-controlled trials were eligible for inclusion. Article abstracts and full texts were screened independently by two reviewers, with disagreements resolved by discussion or a third reviewer if necessary. Five studies were included (n = 587 preterm children). Three compared PRN FOT with spirometry, and two compare it to the interrupter technique. Most studies failed to report comprehensive methodology of the frequency spectra used to generate the PRN signal. There was evidence that poorer lung function, as assessed by PRN FOT, was associated with a greater burden of respiratory symptoms, but there was insufficient evidence to determine whether PRN FOT performed better than other lung-function tests. Detailed methodological documentation, in accordance with ERS guidance, is needed to assess the benefits of PRN FOT prior to routine clinical incorporation to assess prematurely born children. Full article

(This article belongs to the Special Issue Prematurity, Preterm-Born Adults, and Long-Term Effects on Children and Adults)

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