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Real World Data for Population-Based Pediatric Studies

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A special issue of International Journal of Environmental Research and Public Health (ISSN 1660-4601).

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 19356

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Special Issue Editors

Dr. Cristina Canova

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Guest Editor

Unit of Biostatistics, Epidemiology and Public Health, Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padova, Padova, Italy
Interests: population-based birth cohort study; longitudinal studies; environmental epidemiology; pharmacoepidemiology; real-world data
Special Issues, Collections and Topics in MDPI journals

Dr. Claudio Barbiellini Amidei

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Guest Editor

Unit of Biostatistics, Epidemiology and Public Health, Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, 35100 Padua, Italy
Interests: population-based birth cohort study; longitudinal studies; environmental epidemiology; pharmacoepidemiology; real-world data

Special Issue Information

Dear Colleagues,

Progressive digitalization of healthcare services has allowed us to develop, in recent years, unprecedented large-scale population-based studies. Information on drug prescriptions, hospital discharge records, emergency department visits, and other services delivered to the entire population by the National Health Service are availble in an increasing number of countries. By examining healthcare utilization, public health experts, epidemiologists, and researchers can define individual heath profiles, with an overview that can span several decades and will eventually allow for life-long follow-ups.

Studying pediatric health profiles is of particular clinical importance for numerous reasons. Some of its applications consist in analyzing specific pharmacological exposures to investigate associations with the subsequent development of diseases. This is especially relevant considering the vast use of off-label drugs among children, for whom specific clinical trials are rarely conducted.

The association of diseases with other health conditions is also of great relevance, in the attempt to better understand the complexity of comorbidities, to improve diagnostic rapidity, and to indicate possible strategies for targeted prevention among specific groups at increased risks.

Another relevant aspect that will imperatively require further investigation consists in observing possible long-term consequences deriving from the present COVID-19 pandemic. Despite the disease not having shown any serious acute health consequences on children, long-term consequences following Sars-CoV-2 infection are not known.

The most appropriate study design to address these research topics are cohort studies. Pediatric population-based cohorts can be easily built from healthcare databases, using real world data in the attempt to respond to research questions that have not been answered to by gold standard clinical-trials. Healthcare databases can often allow for variably rich adjustments to account for confounders in outcome risk assessment.

When follow-up begins since pregnancy or birth, pediatric cohorts should more appropriately be defined as birth cohorts and can allow for the assessment of exposures in a very delicate phase of life. Heathcare administrative databases can now allow researchers to follow children’s health conditions up to adulthood. This provides the scientific community with a unique opportunity to understand what exposures in utero and in early life mostly affect a correct and healthy growth of the child. These studies can allow policy makers to promote the removal of all detrimental obstactles to an optimal and healthy development of the child.

This Special Issue of the International Journal of Environmental Research and Public Health (IJERPH) focuses on assessing exposures in pediatric population-based cohorts, through record linkage of healthcare administrative databases. High academic standard papers that address these topics are invited for submission to this Special Issue.

Possible topics for this Special Issue include:

1) Pediatric cohorts: real world data for pharmacoepidemiological studies;

2) Pharmacoepidemiology thorough real world data;

3) Pharmacoepidemiology in pregnancy and childhood and the epidemiology of pregnancy and related neonatal complications;

4) Morbid and comorbid COVID-19: beyond the acute phase;

5) Comorbidities in childhood;

6) Non-communicable/preventable diseases among children: where does prevention/public health stand?

7) Exposure to prenatal environmental risk factors (air pollution, chemicals, etc.)—childhood outcomes.

Prof. Dr. Cristina Canova
Dr. Claudio Barbiellini Amidei
Guest Editors

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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. International Journal of Environmental Research and Public Health is an international peer-reviewed open access monthly journal published by MDPI.

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Published Papers (9 papers)

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Research

15 pages, 568 KiB

Open AccessArticle

Epidemiology of Adverse Outcomes in Teenage Pregnancy—A Northeastern Romanian Tertiary Referral Center

by Alexandra Ursache, Ludmila Lozneanu, Iuliana Bujor, Alexandra Cristofor, Ioana Popescu, Roxana Gireada, Cristina Elena Mandici, Marcel Alexandru Găină, Mihaela Grigore and Daniela Roxana Matasariu

Int. J. Environ. Res. Public Health 2023, 20(2), 1226; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph20021226 - 10 Jan 2023

Cited by 1 | Viewed by 2574

Abstract

Background: Despite being a very well-documented subject in the literature, there are still conflicting results regarding teenage pregnancies and their fetal outcomes. Methods: We conducted a retrospective, comparative cohort study that included 1082 mothers aged less than 18 years, compared to 41,998 mothers aged over 18 years, who delivered in our tertiary referral center between January 2015 and December 2021. To check for significant differences between the two groups, the chi-qquared or Fisher’s test for categorical variables were used. Results: We detected statistically significant higher rates of fetal malformation, premature birth, FGR and SGA fetal growth conditions, preeclampsia, condylomatosis and vaginal infection with E. coli in our cohort of teenagers. In this subpopulation of teenagers, the rate for premature birth at less than 32 weeks of gestation was 3.26-fold higher and 3.25-fold higher for condylomatosis, and these results referred to the cohort of adult patients (>18 years old) that gave birth in the same interval of time. Conclusions: Teenage pregnancies still remain a major health problem that burdens all countries worldwide regardless of their income. It needs solutions initially to prevent pregnancy in this young age segment and last but not least to improve both maternal and fetal outcomes. Full article

(This article belongs to the Special Issue Real World Data for Population-Based Pediatric Studies)

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13 pages, 2344 KiB

Open AccessArticle

A Deep Learning Approach to Estimate the Incidence of Infectious Disease Cases for Routinely Collected Ambulatory Records: The Example of Varicella-Zoster

by Corrado Lanera, Ileana Baldi, Andrea Francavilla, Elisa Barbieri, Lara Tramontan, Antonio Scamarcia, Luigi Cantarutti, Carlo Giaquinto and Dario Gregori

Int. J. Environ. Res. Public Health 2022, 19(10), 5959; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph19105959 - 13 May 2022

Cited by 4 | Viewed by 2063

Abstract

The burden of infectious diseases is crucial for both epidemiological surveillance and prompt public health response. A variety of data, including textual sources, can be fruitfully exploited. Dealing with unstructured data necessitates the use of methods for automatic data-driven variable construction and machine learning techniques (MLT) show promising results. In this framework, varicella-zoster virus (VZV) infection was chosen to perform an automatic case identification with MLT. Pedianet, an Italian pediatric primary care database, was used to train a series of models to identify whether a child was diagnosed with VZV infection between 2004 and 2014 in the Veneto region, starting from free text fields. Given the nature of the task, a recurrent neural network (RNN) with bidirectional gated recurrent units (GRUs) was chosen; the same models were then used to predict the children’s status for the following years. A gold standard produced by manual extraction for the same interval was available for comparison. RNN-GRU improved its performance over time, reaching the maximum value of area under the ROC curve (AUC-ROC) of 95.30% at the end of the period. The absolute bias in estimates of VZV infection was below 1.5% in the last five years analyzed. The findings in this study could assist the large-scale use of EHRs for clinical outcome predictive modeling and help establish high-performance systems in other medical domains. Full article

(This article belongs to the Special Issue Real World Data for Population-Based Pediatric Studies)

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11 pages, 1302 KiB

Open AccessArticle

Systemic Steroids in Preventing Bronchopulmonary Dysplasia (BPD): Neurodevelopmental Outcome According to the Risk of BPD in the EPICE Cohort

by Noura Zayat, Patrick Truffert, Elodie Drumez, Alain Duhamel, Julien Labreuche, Michael Zemlin, David Milligan, Rolf F. Maier, Pierre-Henri Jarreau, Héloïse Torchin, Jennifer Zeitlin, Alexandra Nuytten and On behalf of the EPICE Research Group

Int. J. Environ. Res. Public Health 2022, 19(9), 5600; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph19095600 - 05 May 2022

Cited by 2 | Viewed by 2041

Abstract

Background: Postnatal steroids (PNS) have been used to prevent bronchopulmonary dysplasia (BPD) in preterm infants but have potential adverse effects on neurodevelopment. These effects might be modulated by their risk of BPD. We aimed to compare patients’ neurodevelopment with PNS treatment according to their risk of BPD in a European cohort. Methods: We developed a prediction model for BPD to classify infants born between 24 + 0 and 29 + 6 weeks of gestation in three groups and compared patients’ neurological outcome at two years of corrected age using the propensity score (PS) method. Results: Of 3662 neonates included in the analysis, 901 (24.6%) were diagnosed with BPD. Our prediction model for BPD had an area under the ROC curve of 0.82. In the group with the highest risk of developing BPD, PNS were associated with an increased risk of gross motor impairment: OR of 1.95 after IPTW adjustment (95% CI 1.18 to 3.24, p = 0.010). This difference existed regardless of the type of steroid used. However, there was an increased risk of cognitive anomalies for patients treated with dexa/betamethasone that was no longer observed with hydrocortisone. Conclusions: This study suggests that PNS might be associated with an increased risk of gross motor impairment regardless of the group risk for BPD. Further randomised controlled trials exploring the use of PNS to prevent BPD should include a risk-based evaluation of neurodevelopmental outcomes. This observation still needs to be confirmed in a randomised controlled trial. Full article

(This article belongs to the Special Issue Real World Data for Population-Based Pediatric Studies)

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9 pages, 1270 KiB

Open AccessArticle

Confirmatory Factor Analysis of Comorbidity between Depression and Aggression in a Child-Adolescent Community Sample: Nosological, Prognosis and Etiological Implications

by Rodolfo Gordillo, María Victoria Del Barrio Gándara and Miguel A. Carrasco

Int. J. Environ. Res. Public Health 2022, 19(8), 4424; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph19084424 - 07 Apr 2022

Viewed by 1752

Abstract

Comorbidity between depression and aggression in the child-adolescent population remains a controversial phenomenon. To our knowledge, no longitudinal study using structural equation modeling (SEM) has confirmed whether the relationship between depression and aggression is due to the fact that they share internalizing and externalizing supraordinal factors at the level of the syndrome or is due to the fact that they share common characteristics in relation to an underlying factor at the level of symptoms. We examined longitudinal comorbid relationships in a community sample (N = 251) at three waves ages from 10 to 13 years. The SEM showed that longitudinally, the comorbidity between depression and aggression is due to the fact that they share characteristics of the same underlying factor at the symptom level. These results have implications for the classification, diagnosis, and treatment of comorbidity between depression and aggression in a child-adolescent population. Full article

(This article belongs to the Special Issue Real World Data for Population-Based Pediatric Studies)

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9 pages, 744 KiB

Open AccessArticle

Influence of Socio-Economic Factors and Region of Birth on the Risk of Preeclampsia in Sweden

by Kristina Mattsson, Sol Juárez and Ebba Malmqvist

Int. J. Environ. Res. Public Health 2022, 19(7), 4080; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph19074080 - 30 Mar 2022

Cited by 5 | Viewed by 1926

Abstract

Objectives: To investigate the association between socio-economic factors and the risk of preeclampsia in Sweden, specifically investigating if this relationship is confounded by maternal region of birth. Study design: All singleton births between 1999 and 2009 in an ethnically diverse area in southern Sweden, totaling 46,618 pregnancies, were included in this study. The data on maternal pregnancy outcomes were retrieved from a regional birth register and socio-economic variables from Statistics Sweden. The risk ratios for preeclampsia were calculated for educational level and household disposable income, adjusting for maternal region of birth, maternal age, body mass index, parity, and smoking. Results: Low income levels were associated with a higher risk for preeclampsia, adjusted risk ratio (aRR) = 1.25 (95% confidence interval [CI]: 0.99, 1.59) and aRR = 1.36 (95% CI: 1.10, 1.68) for the two lowest quintiles, respectively, compared to the highest. There was an educational gradient in preeclampsia risk, although not all categories reached statistical significance: aRR = 1.16, (95% CI: 0.89–1.50) for low educational attainment and aRR = 1.23 (95% CI: 1.08, 1.41) for intermediate educational attainment compared to women with highest education. The socio-economic gradient remained after adjusting for region of birth. There was a lower risk for preeclampsia for women born in Asia, aRR = 0.60 (95% CI: 0.47, 0.75), regardless of socio-economic position. Conclusion: An increased risk for preeclampsia was seen for women with measures of lower socio-economic position, even in a universal, government-funded healthcare setting. The relationship was not explained by region of birth, indicating that the excess risk is not due to ethnically differential genetic pre-disposition but rather due to modifiable factors. Full article

(This article belongs to the Special Issue Real World Data for Population-Based Pediatric Studies)

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13 pages, 1834 KiB

Open AccessArticle

Association between Exposure to Particulate Matter during Pregnancy and Multidimensional Development in School-Age Children: A Cross-Sectional Study in Italy

by Paolo Girardi, Silvia Lanfranchi, Libera Ylenia Mastromatteo, Massimo Stafoggia and Sara Scrimin

Int. J. Environ. Res. Public Health 2021, 18(21), 11648; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph182111648 - 05 Nov 2021

Cited by 5 | Viewed by 1941

Abstract

Air pollutants can potentially affect the development of children. However, data on the effect of exposure to air pollution during pregnancy and developmental outcomes in school children are rare. We investigated the link between prenatal exposure to particulate matters smaller than 10 microns (PM₁₀) and the development of school-age children in multiple domains. Cross-sectional data were collected in Italy between 2013 and 2014. Children aged between 5 and 8 years (n = 1187) were assessed on cognitive, communication, socio-emotional, adaptive, and motor developmental domains using the Developmental Profile 3 questionnaire. The monthly average concentration of PM₁₀ during the entire fetal period was linked to the municipality of residence of the children. The increase in the prenatal PM₁₀ was associated with a decrease in the cognitive score during the second (+13.2 µg/m³ PM₁₀ increase: −0.30 points; 95%CI: −0.12–−0.48) and third trimesters of pregnancy (−0.31 points; 95%CI: −0.11–−0.50). The communicative domain was also negatively influenced by PM₁₀ increases in the second trimester. The development of cognitive and communicative abilities of children was negatively associated with the exposure to PM₁₀ during the period of fetal development, confirming that exposure to air pollution during pregnancy can potentially hinder the development of the brain. Full article

(This article belongs to the Special Issue Real World Data for Population-Based Pediatric Studies)

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12 pages, 334 KiB

Open AccessArticle

Conduct Disorder in Immigrant Children and Adolescents: A Nationwide Cohort Study in Sweden

by Mehdi Osooli, Henrik Ohlsson, Jan Sundquist and Kristina Sundquist

Int. J. Environ. Res. Public Health 2021, 18(20), 10643; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph182010643 - 11 Oct 2021

Viewed by 1790

Abstract

Introduction. Conduct disorder is a psychiatric diagnosis characterized by repetitive and persistent norm-breaking behavior. This study aimed to compare the risk of conduct disorder between first- and second-generation immigrant children and adolescents and their native controls. Methods. In this nationwide, open-cohort study from Sweden, participants were born 1987–2010, aged 4–16 years at baseline, and were living in the country for at least one year during the follow-up period between 2001 and 2015. The sample included 1,902,526 and 805,450 children-adolescents with native and immigrant backgrounds, respectively. Data on the conduct disorder diagnoses were retrieved through the National Patient Register. We estimated the incidence of conduct disorder and calculated adjusted Hazard Ratios. Results. Overall, the adjusted risk of conduct disorder was lower among first-generation immigrants and most second-generation immigrant groups compared with natives (both males and females). However, second-generation immigrants with a Swedish-born mother and a foreign-born father had a higher risk of conduct disorder than natives. Similar results were found for sub-diagnoses of conduct disorder. Conclusions. The higher risk of conduct disorder among second-generation immigrants with a Swedish-born mother and the lower risk among most of the other immigrant groups warrants special attention and an investigation of potential underlying mechanisms. Full article

(This article belongs to the Special Issue Real World Data for Population-Based Pediatric Studies)

13 pages, 1426 KiB

Open AccessArticle

Association of Treated and Untreated Gastroesophageal Reflux Disease in the First Year of Life with the Subsequent Development of Asthma

by Anna Cantarutti, Claudio Barbiellini Amidei, Camilla Valsecchi, Antonio Scamarcia, Giovanni Corrao, Dario Gregori, Carlo Giaquinto, Jonas F. Ludvigsson and Cristina Canova

Int. J. Environ. Res. Public Health 2021, 18(18), 9633; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph18189633 - 13 Sep 2021

Cited by 7 | Viewed by 2142

Abstract

Introduction: Gastroesophageal reflux disease (GERD) as well as its treatment with acid-suppressive medications have been considered possible risk factors for the development of asthma, but few studies have disentangled the role of GERD with that of its treatment. The present study aimed at estimating the association of treated and untreated GERD in the first year of life with the risk of asthma. Methods: Retrospective cohort study including all children born between 2004 and 2015 registered in Pedianet, an Italian primary care database. We analyzed the association of children exposed to GERD (both treated and untreated) in the first year of life with the risk of developing clinically assessed asthma (clinical asthma) after 3 years. Secondary outcomes included asthma identified by anti-asthmatic medications (treated asthma) and wheezing after 3 years. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated comparing children with and without GERD, stratifying by treatment with acid-suppressive medications. Results: Out of 86,381 children, 1652 (1.9%) were affected by GERD in the first year of life, of which 871 (53%) were treated with acid-suppressive medications. Compared with controls, children with GERD were at increased risk of clinical asthma (HR: 1.40, 95% CI 1.15–1.70). Risks were similar between treated and untreated GERD (p = 0.41). Comparable results were found for treated asthma, but no risk increase was seen for wheezing. Discussion: Early-life GERD was associated with subsequent childhood asthma. Similar risks among children with treated and untreated GERD suggest that acid-suppressive medications are unlikely to play a major role in the development asthma. Full article

(This article belongs to the Special Issue Real World Data for Population-Based Pediatric Studies)

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9 pages, 318 KiB

Open AccessArticle

Use of the Bacterial Lysate OM-85 in the Paediatric Population in Italy: A Retrospective Cohort Study

by Anna Cantarutti, Elisa Barbieri, Antonio Scamarcia, Luigi Cantarutti, Cristina Canova and Carlo Giaquinto

Int. J. Environ. Res. Public Health 2021, 18(13), 6871; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph18136871 - 26 Jun 2021

Cited by 4 | Viewed by 1950

Abstract

Background: In Italy, the bacterial lysate OM-85 (Broncho-Vaxom^®, Broncho-Munal^®, Ommunal^®, Paxoral^®, Vaxoral^®) is registered for the prophylaxis of recurrent respiratory tract infections (RTIs) in adults and children above one year of age, but there are limited data on its use in the paediatric population. We aim to estimate the impact of OM-85 treatment on RTIs and antibiotic prescriptions in children. Methods: This study included children aged 1 to 14 years enrolled in Pedianet, a paediatric general practice research database, from January 2007 to June 2017, having at least one prescription of OM-85. Children with less than 12 months of follow-up before (PRE period) and after (POST period) the OM-85 prescription were excluded. The frequency of antibiotic prescriptions and the frequency of RTI episodes in the PRE and POST periods were compared through the post-hoc test. Subgroup analysis was performed in children with recurrent RTIs. Results: 1091 children received 1382 OM-85 prescriptions for a total follow-up of 619,525.5 person-years. Overall, antibiotic prescriptions decreased from a mean of 2.8 (SD (standard deviation) 2.7) prescriptions in the PRE period to a mean of 2.2 (SD 2.6) prescriptions in the POST period (p < 0.0001). RTIs decreased from a mean of 3.4 (SD 2.9) episodes in the PRE period to a mean of 2.5 (SD 2.6) episodes in the POST period (p < 0.0001). No change in antibiotic class was noted, and co-amoxiclav remained the preferred therapy in 28% of cases, followed by amoxicillin. These results were confirmed among children with recurrent RTIs. Conclusions: OM-85 is effective in preventing both antibiotic prescriptions and RTIs in children. Full article

(This article belongs to the Special Issue Real World Data for Population-Based Pediatric Studies)

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