Publications by authors named "Maria Pierro"

13 Publications

  • Page 1 of 1

Association of the dysfunctional placentation endotype of prematurity with bronchopulmonary dysplasia: a systematic review, meta-analysis and meta-regression.

Thorax 2021 Jul 23. Epub 2021 Jul 23.

Pediatrics, Maastricht University Medical Centre, School for Oncology and Developmental Biology (GROW), Maastricht, The Netherlands

Background: Antenatal pathological conditions are key in the pathogenesis of bronchopulmonary dysplasia (BPD). Pathophysiological pathways or endotypes leading to prematurity and perinatal lung injury can be clustered into two groups: infection and dysfunctional placentation, which include hypertensive disorders of pregnancy (HDP) and intrauterine growth restriction (IUGR). We conducted a systematic review of observational studies exploring the association between the dysfunctional placentation endotype and BPD.

Methods: MEDLINE, Embase and Web of Science databases were searched up to February 2020 for studies reporting data on the diagnosis of HDP, IUGR or small for gestational age (SGA) and BPD risk. BPD was classified as BPD28 (supplemental oxygen on day 28), BPD36 (oxygen at 36 weeks postmenstrual age), severe BPD (≥ 30% oxygen or mechanical ventilation), BPD36/death and BPD-associated pulmonary hypertension.

Results: Of 6319 studies screened, 211 (347 963 infants) were included. Meta-analysis showed an association between SGA/IUGR and BPD36 (OR 1.56, 95% CI 1.37 to 1.79), severe BPD (OR 1.82, 95% CI 1.36 to 2.29) and BPD/death (OR 1.91, 95% CI 1.55 to 2.37). Exposure to HDP was not associated with BPD but was associated with decreased odds of BPD/death (OR 0.77, 95% CI 0.64 to 0.94). Both HDP (OR 1.41, 95% CI 1.10 to 1.80) and SGA/IUGR (OR 2.37, 95% CI 1.86 to 3.02) were associated with BPD-associated pulmonary hypertension.

Conclusion: When placental vascular dysfunction is accompanied by fetal growth restriction or being born SGA, it is associated with an increased risk of developing BPD and pulmonary hypertension. The placental dysfunction endotype of prematurity is strongly associated with the vascular phenotype of BPD.

Prospero Registration Number: Review protocol was registered in PROSPERO database (ID=CRD42018086877).
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http://dx.doi.org/10.1136/thoraxjnl-2020-216485DOI Listing
July 2021

Mother's Own Milk and Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis.

Front Pediatr 2019 6;7:224. Epub 2019 Jun 6.

Department of Pediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center (MUMC+), Maastricht, Netherlands.

Bronchopulmonary dysplasia (BPD) is the most common complication of very preterm birth and can lead to lifelong health consequences. Optimal nutrition is a cornerstone in the prevention and treatment of BPD. In very preterm infants, mother's own milk (MOM) feeding is associated with lower risks of necrotizing enterocolitis, retinopathy of prematurity, and sepsis. Although several studies have shown that MOM may protect against BPD, a systematic analysis of the evidence has not been performed to date. A comprehensive literature search was conducted using PubMed/MEDLINE and EMBASE, from their inception to 1 December 2017. Longitudinal studies comparing the incidence of BPD in preterm infants fed with exclusive MOM, MOM supplemented with preterm formula (PF), and/or exclusively fed with PF were selected. A random-effects model was used to calculate the Mantel Haenszel risk ratio (RR) and 95% confidence interval (CI). Fifteen studies met the inclusion criteria (4,984 infants, 1,416 BPD cases). Use of exclusive MOM feedings was associated with a significant reduction in the risk of BPD (RR 0.74, 95% CI 0.57-0.96, 5 studies). In contrast, meta-analysis could not demonstrate a significant effect on BPD risk when infants fed with more than 50% MOM were compared with infants fed with <50% MOM (RR 0.98, 95% CI 0.77-1.23, 10 studies) or when infants fed with MOM supplemented with PF were compared with infants fed with exclusive PF (RR 1.00, 95% CI 0.78-1.27, 6 studies). Meta-regression showed that differences in gestational age were a significant confounder of the effect of MOM. To our knowledge, this is the first systematic review and meta-analysis that specifically evaluates the role of MOM on BPD. Our data indicate that MOM may reduce the incidence of BPD when used as an exclusive diet, but this result needs to be interpreted with caution. We did not find the same difference in analyses with other dosages of MOM. Further studies adequately powered to detect changes in BPD rates and that adjust for confounders are needed to confirm the beneficial effects of MOM on BPD.
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http://dx.doi.org/10.3389/fped.2019.00224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593284PMC
June 2019

Donor Human Milk Protects against Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis.

Nutrients 2018 Feb 20;10(2). Epub 2018 Feb 20.

Department of Pediatrics, Maastricht University Medical Center (MUMC+), School for Oncology and Developmental Biology (GROW), 6202 AZ Maastricht, The Netherlands.

Bronchopulmonary dysplasia (BPD) is the most common complication after preterm birth. Pasteurized donor human milk (DHM) has increasingly become the standard of care for very preterm infants over the use of preterm formula (PF) if the mother's own milk (MOM) is unavailable. Studies have reported beneficial effects of DHM on BPD. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies on the effects of DHM on BPD and other respiratory outcomes. Eighteen studies met the inclusion criteria. Meta-analysis of RCTs could not demonstrate that supplementation of MOM with DHM reduced BPD when compared to PF (three studies, risk ratio (RR) 0.89, 95% confidence interval (CI) 0.60-1.32). However, meta-analysis of observational studies showed that DHM supplementation reduced BPD (8 studies, RR 0.78, 95% CI 0.67-0.90). An exclusive human milk diet reduced the risk of BPD, compared to a diet with PF and/or bovine milk-based fortifier (three studies, RR 0.80, 95% CI 0.68-0.95). Feeding raw MOM, compared to feeding pasteurized MOM, protected against BPD (two studies, RR 0.77, 95% CI 0.62-0.96). In conclusion, our data suggest that DHM protects against BPD in very preterm infants.
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http://dx.doi.org/10.3390/nu10020238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852814PMC
February 2018

Mesenchymal stem cells for the prevention and treatment of bronchopulmonary dysplasia in preterm infants.

Cochrane Database Syst Rev 2017 Nov 10;11:CD011932. Epub 2017 Nov 10.

Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.

Background: Bronchopulmonary dysplasia (BPD) remains a major complication of prematurity and currently lacks efficient treatments. Mesenchymal stem/stromal cells (MSCs) have been extensively explored as a potential therapy in several preclinical and clinical settings. Human and animal MSCs have been shown to prevent and treat lung injury in various preclinical models of lung diseases, including experimental BPD.

Objectives: To determine if MSCs, administered intravenously or endotracheally, are safe and effective in preventing or treating BPD, or both, in preterm infants.

Search Methods: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 10), MEDLINE via PubMed (1966 to 6 November 2016), Embase (1980 to 6 November 2016), and CINAHL (1982 to 6 November 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-RCTs.

Selection Criteria: We considered RCTs and quasi-RCTs investigating prevention or treatment of BPD, or both, in preterm infants.

Data Collection And Analysis: Two review authors independently assessed trial quality according to prespecified criteria.

Main Results: We found no RCTs or quasi-RCTs addressing the use of MSCs for prevention or treatment of BPD in premature infants. Two RCTs are currently registered and ongoing.

Authors' Conclusions: There is insufficient evidence to determine the safety and efficacy of MSCs in the treatment or prevention of BPD in premature infants. The results of the ongoing trials addressing this issue are expected in the near future.
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http://dx.doi.org/10.1002/14651858.CD011932.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485972PMC
November 2017

Probiotic Supplementation in Preterm Infants Does Not Affect the Risk of Bronchopulmonary Dysplasia: A Meta-Analysis of Randomized Controlled Trials.

Nutrients 2017 Oct 31;9(11). Epub 2017 Oct 31.

Department of Pediatrics, Maastricht University Medical Center (MUMC+), School for Oncology and Developmental Biology (GROW), 6202 AZ Maastricht, The Netherlands.

Probiotic supplementation reduces the risk of necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in preterm infants, but it remains to be determined whether this reduction translates into a reduction of other complications. We conducted a systematic review and meta-analysis to evaluate the possible role of probiotics in altering the risk of bronchopulmonary dysplasia (BPD). Fifteen randomized controlled trials (4782 infants; probiotics: 2406) were included. None of the included studies assessed BPD as the primary outcome. Meta-analysis confirmed a significant reduction of NEC (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.33 to 0.81, = 0.004; random effects model), and an almost significant reduction of LOS (RR 0.82, 95% CI 0.65 to 1.03, = 0.084). In contrast, meta-analysis could not demonstrate a significant effect of probiotics on BPD, defined either as oxygen dependency at 28 days of life (RR 1.01, 95% CI 0.91 to 1.11, = 0.900, 6 studies) or at 36 weeks of postmenstrual age (RR 1.07, 95% CI 0.96 to 1.20, = 0.203, 12 studies). Meta-regression did not show any significant association between the RR for NEC or LOS and the RR for BPD. In conclusion, our results suggest that NEC and LOS prevention by probiotics does not affect the risk of developing BPD in preterm infants.
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http://dx.doi.org/10.3390/nu9111197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707669PMC
October 2017

Bronchopulmonary Dysplasia and Chronic Lung Disease: Stem Cell Therapy.

Clin Perinatol 2015 Dec;42(4):889-910

Division of Neonatology, Department of Pediatrics, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON K1H 8L1, Canada; Regenerative Medicine Program, Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, The Ottawa Hospital, 501 Smyth Road, Ottawa, Ontario K1H8L6, Canada; Department of Cellular and Molecular Medicine, Sinclair Institute of Regenerative Medicine, University of Ottawa, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada.

Bronchopulmonary dysplasia (BPD), a major complication of premature birth, still lacks safe and effective treatment. Mesenchymal stem cells (MSCs) have been proven to ameliorate critical aspects of the BPD pathogenesis. MSCs seem to exert therapeutic effects through the paracrine secretion of anti-inflammatory, antioxidant, antiapoptotic, trophic, and proangiogenic factors. Although these findings are promising, understanding the mechanism of action of MSCs and MSC manufacturing is still evolving. Several aspects can affect the efficacy of MSC therapy. Further research is required to optimize this potentially game-changing treatment but the translation of regenerative cell therapies for patients has begun.
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http://dx.doi.org/10.1016/j.clp.2015.08.013DOI Listing
December 2015

Oxygen administration at birth in preterm infants: a retrospective analysis.

J Matern Fetal Neonatal Med 2016 30;29(16):2675-80. Epub 2015 Oct 30.

a NICU, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università Degli Studi Di Milano , Milan , Italy and.

Objective: The aim of the study was to retrospectively investigate the association between initial oxygen concentration in delivery room and short-term outcomes in preterm infants.

Methods: Data from infants needing neonatal resuscitation, born at our department between January 2008 and December 2011, were analyzed. Patients were divided into three groups based on gestational age: between 32 and 36 weeks, between 31 and 28 weeks, and below 28 weeks.

Results: The administration of each additional unit of oxygen up to 50% showed an association with a 5% increased need for mechanical ventilation (MV) in the neonatal intensive care unit in infants between 32 and 36 weeks [adjusted odds ratio 1.1, 95% confidence interval (CI) 1.04-1.1] and infants between 28 and 31 weeks (adjusted odds ratio 1.12, 95% CI 1.08-1.44). On the contrary, in infants below 28 weeks, increasing initial concentration of supplementary oxygen did not show any association with MV.

Conclusions: Initial oxygen concentration seems to be associated with increased MV in the NICU. Our observations further stress the need for randomized controlled studies in order to obtain definitive recommendations for the optimal initial oxygen concentration during neonatal resuscitation of preterm infants.
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http://dx.doi.org/10.3109/14767058.2015.1100161DOI Listing
January 2017

Short-term, long-term and paracrine effect of human umbilical cord-derived stem cells in lung injury prevention and repair in experimental bronchopulmonary dysplasia.

Thorax 2013 May 4;68(5):475-84. Epub 2012 Dec 4.

Department of Pediatrics, Cardiovascular Research Center and Pulmonary Research Group, School of Human Development, Women and Children's Health Research Institute, University of Alberta, Edmonton, Canada.

Background: Bronchopulmonary dysplasia (BPD) remains a main complication of extreme prematurity and currently lacks efficient treatment. Rat bone marrow-derived mesenchymal stem cells (MSC) prevent lung injury in an oxygen-induced model of BPD. Human cord is an advantageous source of stem cells that is especially appealing for the treatment of neonatal diseases. The therapeutic benefit after established lung injury and long-term safety of cord-derived stem cells is unknown.

Methods: Human cord-derived perivascular cells (PCs) or cord blood-derived MSCs were delivered prophylactically or after established alveolar injury into the airways of newborn rats exposed to hyperoxia, a well-established BPD model.

Results: Rat pups exposed to hyperoxia showed the characteristic arrest in alveolar growth with air space enlargement and loss of lung capillaries. PCs and MSCs partially prevented and rescued lung function and structure. Despite therapeutic benefit, cell engraftment was low, suggesting that PCs and MSCs act via a paracrine effect. Accordingly, cell free-derived conditioned media from PCs and MSCs also exerted therapeutic benefit when used either prophylactically or therapeutically. Finally, long-term (6 months) assessment of stem cell or conditioned media therapy showed no adverse lung effects of either strategy, with persistent improvement in exercise capacity and lung structure.

Conclusions: Human umbilical cord-derived PCs and MSCs exert short- and long-term therapeutic benefit without adverse lung effects in this experimental model and offer new therapeutic options for lung diseases characterised by alveolar damage.
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http://dx.doi.org/10.1136/thoraxjnl-2012-202323DOI Listing
May 2013

Nasal continuous positive airway pressure with heliox in preterm infants with respiratory distress syndrome.

Pediatrics 2012 Feb 30;129(2):e333-8. Epub 2012 Jan 30.

NICU, Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.

Objective: To assess the therapeutic effects of breathing a low-density helium and oxygen mixture (heliox, 80% helium and 20% oxygen) in premature infants with respiratory distress syndrome (RDS) treated with nasal continuous positive airway pressure (NCPAP).

Methods: Infants born between 28 and 32 weeks of gestational age with radiologic findings and clinical symptoms of RDS and requiring respiratory support with NCPAP within the first hour of life were included. These infants were randomly assigned to receive either standard medical air (control group) or a 4:1 helium and oxygen mixture (heliox group) during the first 12 hours of enrollment, followed by medical air until NCPAP was no longer needed.

Results: From February 2008 to September 2010, 51 newborn infants were randomly assigned to two groups, 24 in the control group and 27 in the heliox group. NCPAP with heliox significantly decreased the risk of mechanical ventilation in comparison with NCPAP with medical air (14.8% vs 45.8%).

Conclusions: Heliox increases the effectiveness of NCPAP in the treatment of RDS in premature infants.
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http://dx.doi.org/10.1542/peds.2011-0532DOI Listing
February 2012

Mesenchymal stem cells in chronic lung disease: culprit or savior?

Am J Physiol Lung Cell Mol Physiol 2010 Jun 2;298(6):L732-4. Epub 2010 Apr 2.

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http://dx.doi.org/10.1152/ajplung.00099.2010DOI Listing
June 2010

[Respiratory failure in "late preterm" infants: a retrospective cohort study].

Pediatr Med Chir 2009 Nov-Dec;31(6):241-5

UO di Neonatologia, Ospedale San Giuseppe, Milano.

Objective: To evaluate the incidence and characteristics of the respiratory failure in late preterm infants.

Study Design: Retrospective data analysis in years 2006-2007 in late preterm infants (GA 34(+0)-36(+6) weeks) with respiratory failure, admitted at a tertiary level NICU.

Result: Data from 1011 late preterm infants, which accounted for 7% of all deliveries and 65% of preterm births were analyzed; 29% (292/1011) required intensive care and 13% (136/1011) presented respiratory failure (16% of all ventilated infants in the period). In late preterms with respiratory failure 23% (32/136) were treated with prenatal steroids 46% (62/136) with non -invasive ventilation (nasal continuous positive airways pressure = nCPAP) while 41% (56/136) were intubated and received exogenous surfactant. Mean days of ventilation were 5.3 +/- 6.5 (0.5-55); 3.7% (5/136) developed bronchopulmonary dysplasia defined as oxygen-dependency at 36 postconceptional age and mortality was 1.5% (2/136).

Conclusion: Respiratory failure incidence and characteristics in late preterms suggest their peculiarity and relevance in neonatal intensive care.
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April 2010

HLA-DQ2 and -DQ8 genotypes in celiac and healthy Libyan children.

Dig Liver Dis 2010 Jun 12;42(6):425-7. Epub 2009 Oct 12.

Department of Pediatrics, Omar Al Mukhtar University, Al Bayda, Libya.

Background: Few data are available on the prevalence of celiac disease (CD)-predisposing, HLA-related genes in Arab populations.

Aim Of The Study: To investigate the distribution of HLA-DQ2 and -DQ8 genotypes in Libyan children with CD and healthy controls.

Patients: We tested 31 Libyan children with CD (22 females and 9 males, median age 9.2 years) and 156 Libyan controls (81 females and 75 males, median age 10.9).

Methods: HLA genes were determined on a drop of dried blood by the DQ-CD Typing Plus kit (DiaGene, Palermo, Italy).

Results: The HLA-DQ pattern of the 31 CD children was: hetero DQ2 (n=15), DQ2 with homo beta2 (10), DQ8 and beta2 positive (3), DQ8 (2), and hetero beta2 (1). The HLA-DQ pattern of the 156 controls was: hetero DQ2 (n=36), hetero beta2 (30), DQ2-DQ8 negative (23), DQ8 (19), alpha5 (14), DQ2 with homo beta (12), homo beta2 (10), DQ8 and beta2 positive (7), and DQ2/DQ8 (5).

Conclusions: HLA-DQ2 and -DQ8 in CD patients are as common in Libya as in Italy, but the frequency of "high-risk" genotypes is higher in Libyan than Italian patients. The prevalence of HLA-DQ2 and -DQ8 genes in the Libyan general population is higher than in Italy, indicating a strong genetic predisposition to CD.
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http://dx.doi.org/10.1016/j.dld.2009.09.004DOI Listing
June 2010
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