Next Article in Journal
Mental Health Professionals’ Views on Artificial Intelligence as an Aide for Children Anticipating or Suffering the Loss of a Parent to Cancer: Helpful or Harmful?
Previous Article in Journal
Changes in Motor Function in a Child with Cerebral Palsy Following Multiple Botulinum Toxin Injections: A Case Report
Previous Article in Special Issue
The Role of Genetic Testing in Palliative Care Decisions for Critically Ill Newborns
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Children
Volume 12
Issue 6
10.3390/children12060762
children-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Systematic Review

Association Between Hypertensive Disorders of Pregnancy and Patent Ductus Arteriosus in Very Preterm Infants: A Bayesian Model-Averaged Meta-Analysis

by
Moreyba Borges-Luján
1,
Gloria Galán-Henríquez
1,
Rosa I. Rodríguez-Viera
1,
František Bartoš
2,
Gema E. González-Luis
1 and
Eduardo Villamor
3,*
1
Department of Pediatrics, Hospital Universitario Materno-Infantil de Canarias, 35016 Las Palmas de Gran Canaria, Spain
2
Department of Psychology, University of Amsterdam, 1018WS Amsterdam, The Netherlands
3
Division of Neonatology, MosaKids Children’s Hospital, Maastricht University Medical Center (MUMC+), Research Institute for Oncology and Reproduction (GROW), Maastricht University, 6202AZ Maastricht, The Netherlands
*
Author to whom correspondence should be addressed.
Children 2025, 12(6), 762; https://doi.org/10.3390/children12060762
Submission received: 16 May 2025 / Revised: 3 June 2025 / Accepted: 10 June 2025 / Published: 12 June 2025
(This article belongs to the Special Issue Advances in Intensive Care for Critically Ill Neonates: Clinical Diagnosis and Treatment)
Browse Figures
Versions Notes

Abstract

:
Background/Objectives: Prenatal adverse events may influence the development of complications of prematurity, including patent ductus arteriosus (PDA). We conducted a systematic review and Bayesian model-averaged (BMA) meta-analysis of observational studies exploring the association between hypertensive disorders of pregnancy (HDP) and the risk of PDA in preterm infants. Methods: PubMed/Medline and Embase databases were searched. We used BMA analysis to calculate Bayes factors (BFs). The BF10 is the ratio of the probability of the data under the alternative hypothesis (H1, presence of association) over the probability of the data under the null hypothesis (H0, absence of association). Results: We included 41 studies (58,004 infants). BMA analysis showed moderate evidence in favour of H0 for the association between HDP and any PDA (BF10 = 0.20) as well as for the association between HDP and hemodynamically significant PDA (BF10 = 0.27). Subgroup analyses based on the subtype of HDP showed that the moderate evidence in favour of H0 was only conclusive (i.e., BF10 < 0.33) for the associations of any PDA with preeclampsia (BF10 = 0.30) and hemodynamically significant PDA with preeclampsia (BF10 = 0.17). Conclusions: The currently available evidence suggests a lack of association between HDP and the risk of developing PDA.

1. Introduction

The closure of the ductus arteriosus (DA) at birth is a central event in the transition from foetal to neonatal circulation [1,2,3,4]. In very and extremely preterm infants (i.e., gestational age < 32 weeks), ductal closure is frequently delayed or fails, resulting in a clinical situation referred to as patent ductus arteriosus (PDA). Diagnosing and managing PDA is a key part of the neonatal intensive care practice [1,2,3,4].
Precision or personalized medicine is becoming an overarching medical discipline that requires a better understanding of genotypes, endotypes, and clinical phenotypes of diseases [5]. The term endotype refers to “a subtype of a condition, which is defined by a distinct functional or pathophysiological mechanism” [6]. Despite the absence of a definitive consensus on the identification of endotypes associated with prematurity, the integration of clinical data with placental and bacteriological information allows for the delineation of two predominant pathways leading to very and extremely preterm birth: infection/inflammation and dysfunctional placentation [7,8,9]. The first group includes chorioamnionitis, pre-labour premature rupture of the membranes, and cervical insufficiency [7,8,9]. The second group is defined by the presence of histologic features indicative of placental vascular dysfunction. This group is associated with hypertensive disorders of pregnancy (HDP) and the condition is referred to as foetal indication/intrauterine growth restriction (IUGR) [7,8,9]. The environment to which the developing foetus is exposed varies greatly between the two endotypes of prematurity. In the infectious endotype, the response is inflammatory, with a release of cytokines and other inflammatory mediators, whereas in the placental dysfunction endotype, there is chronic hypoxia and imbalance of angiogenic mediators [7,8,9]. Therefore, the different endotypes may have a variable potential to induce the different complications of prematurity [7,8,9].
Our group has recently analysed the association between the different endotypes of prematurity and its major complications, including PDA [10,11,12,13]. We observed a statistically significant (p < 0.001) association between chorioamnionitis and the risk of developing PDA [10]. The odds ratio (OR) was 1.35 with a 95% confidence interval (CI) of 1.17 to 1.56. However, this association was strongly related to the lower gestational age (GA) of infants exposed to chorioamnionitis compared to those not exposed [10]. Regarding the endotype of placental dysfunction, we examined the association between PDA and IUGR in another meta-analysis [13]. We found a statistically significant association (OR 0.82, 95% CI 0.70 to 0.96, p = 0.015) between growth restriction (defined as IUGR or small for GA) and the risk of developing PDA. However, this statistical significance was not present (OR 0.87, 95% CI 0.72 to 1.04, p = 0.133) when only hemodynamically significant PDA (hsPDA) was taken into account [13].
HDP, including preeclampsia, eclampsia, and gestational hypertension, are among the most common causes of preterm birth and are often associated with the various complications of prematurity [14]. As mentioned above, HDP are among the conditions considered to be part of the endotype of placental dysfunction [12]. Of note, the potential association between HDP and PDA has not been the subject of extensive investigation. In a meta-analysis published in 2021, Liu et al. examined the relationship between various antenatal conditions and PDA [15]. They included eight studies that reported on rates of preeclampsia and PDA and found no statistically significant association between the two conditions (OR 0.89, 95% CI 0.68–1.17, p = 0.406). Our objective in the present study was to perform a systematic review and meta-analysis of the potential association between HDP and the risk of developing PDA. Instead of the more commonly utilized frequentist statistics, including p-values and confidence intervals, a Bayesian approach was used for the meta-analysis. A key limitation of frequentist null hypothesis significance testing is that failing to reject the null hypothesis (H0) when the p-value is below a predetermined threshold (typically 0.05) or the confidence interval intersects the line of no effect does not necessarily indicate evidence for H0 [16]. The Bayesian approach allows for the assessment of the strength of the evidence in relation to both H0 (absence of effect/association) and the alternative hypothesis (H1, presence of effect/association) [16].

2. Materials and Methods

This study was performed and reported according to the preferred reporting items for systematic reviews and meta-analyses of observational studies in epidemiology guidelines. Review protocol was registered in PROSPERO database (ID = CRD42020184843). The Population, Exposure, Comparison, and Outcome (PECO) question was: Do preterm infants (P) exposed to HDP (E) have a higher risk of developing PDA (O) than preterm infants with no history of exposure (C)?
  • Sources and search strategy
A comprehensive literature search was undertaken using the PubMed and Embase databases. The search strategy is detailed in Supplementary Table S1. No language limit was applied. The literature search was updated up to February 2024.
  • Study selection and definitions
Studies were included if they had a prospective or retrospective cohort or case-control design, examined very and extremely preterm infants (GA ≤ 32 weeks), and reported primary data that could be used to measure the association between exposure to HDP and PDA. The reason for focusing on very and extremely preterm infants was that the risk of PDA increases as GA decreases [1,2,3,4]. The studies were divided according to the way they considered small ductal shunts. Studies comparing closed DA vs. small plus large PDA were classified as reporting on “any PDA”. Studies comparing closed DA and/or small PDA vs. large PDA were classified as reporting on “hemodynamically significant PDA” (hsPDA). In the absence of a universally accepted definition of hsPDA, any definition included in the original studies was accepted for the purposes of this analysis. PDA requiring treatment was considered a proxy for hsPDA. The HDP category was further subdivided into preeclampsia, preeclampsia/HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) syndrome, and “any HDP”. As with PDA, any definition of HDP, preeclampsia, or HELLP syndrome provided by the original studies was accepted for the purposes of this analysis.
To identify relevant studies, two reviewers (GGL and EV) independently screened the results of the searches and applied inclusion criteria using a structured form. Discrepancies were identified and resolved through discussion or in consultation with the other researchers.
  • Data extraction and assessment of risk of bias
Three investigators (MB-L, GG-H, and RR-V) extracted data on the study design, demographics, and rate of PDA. A second group of investigators (GG-L and EV) checked the data extraction for completeness and accuracy. Risk of bias was assessed using the Newcastle–Ottawa scale (NOS) for cohort or case-control studies [17]. NOS scores ≥ 7 were considered indicative of low risk of bias and scores of 5 to 6 as indicative of moderate risk of bias.
  • Bayesian model-averaged meta-analysis
The effect size of dichotomous variables was expressed as logOR and the effect size of continuous variables was expressed using the Hedges’ g. Values of logOR and Hedges’ g and the corresponding standard error of each individual study were pooled and analysed by a Bayesian model-averaged (BMA) meta-analysis [18,19]. We performed the BMA analysis in JASP, which utilizes the RoBMA R package [20]. BMA analysis employs Bayes factors (BFs) and Bayesian model-averaging to evaluate the likelihood of the data under the combination of models assuming the presence vs. the absence of the meta-analytic effect and heterogeneity [18,19]. The BF10 is the ratio of the probability of the data under H1 over the probability of the data under H0. The BF10 was interpreted using the evidence categories suggested by Lee and Wagenmakers [21]: <1/100 = extreme evidence for H0, from 1/100 to <1/30 = very strong evidence for H0, from 1/30 to <1/10 = strong evidence for H0, from 1/10 to <1/3 = moderate evidence for H0, from 1/3 to <1 weak/inconclusive evidence for H0, from 1 to 3 = weak/inconclusive evidence for H1, from >3 to 10 = moderate evidence for H1, from >10 to 30 = strong evidence for H1, from >30 to 100 = very strong evidence for H1, and >100 extreme evidence for H1. The BFrf is the ratio of the probability of the data under the random-effects model over the probability of the data under the fixed-effects model.
We used robust Bayesian meta-analysis (RoBMA) to assess the robustness of the results to the potential presence of publication bias, which was expressed as BFbias [22]. The potential moderating effect of the difference in GA (the mean GA of the HDP-exposed group minus the mean GA of the non-exposed group in each individual study) on the association between HDP and PDA was investigated through Bayesian model-averaged meta-regression (BMA-reg) and expressed as BFmod [23]. The categories of strength of the evidence in favour of the random effects (BFrf > 1) or the fixed effect (BFrf < 1), presence vs. absence of publication bias (BFbias >1 vs. BFbias <1), or presence vs. absence of moderation by GA (BFmod > 1 vs. BFmod < 1) were similar to those described above for the BF10.
For all the analyses, we used the neonatal-specific empirical prior distributions based on the Cochrane Database of Systematics Reviews [18]. Binary outcomes: logOR ~ Student-t (µ = 0, σ = 0.29, ν = 3), tau (logRR) ~ Inverse-Gamma (k = 1.80, θ = 0.42); Continuous outcomes: Cohen’s d~Student-t (µ = 0, σ = 0.42, ν = 5), tau (Cohen’s d)~Inverse-Gamma (k = 1.68, θ = 0.38) [18]. For the meta-regression, we used the prior distributions for the effect size and heterogeneity parameter with the prior distribution on the standardized meta-regression coefficient scaled by 1/2 (i.e., the expected difference in each moderator level corresponding to 1/2 of the mean effect size) [23]. To test the robustness of this analysis, another meta-regression was conducted with the prior distribution on the standardized meta-regression coefficient scaled by 1/4 (Supplementary Table S3).

3. Results

3.1. Description of Studies and Risk of Bias Assessment

Of 1159 potentially relevant studies, 41 (58,004 infants) were included [24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64] (Figure 1). Their characteristics are summarized in Supplementary Table S2. Two studies were case-control studies and the other 39 were cohort studies. Sixteen studies were prospective and 25 were retrospective. Sixteen studies reported on any PDA, 24 reported on hsPDA, and one study reported on both any PDA and hsPDA. The quality score of each study according to the NOS is depicted in Supplementary Table S2. All studies received a score of six or higher, indicating a low to moderate risk of bias.

3.2. Bayesian Model-Averaged Meta-Analysis

Figure 2 and Figure 3 and Table 1 summarize the results of the BMA meta-analysis. LogOR was converted to OR for clarity. BMA analysis showed moderate evidence in favour of H0 (absence of association) for the association between HDP and any PDA (BF10 = 0.20, Figure 2, Table 1) as well as for the association between HDP and hsPDA (BF10 = 0.27, Figure 3, Table 1). BMA analysis showed extreme evidence of heterogeneity (BFrf > 100) for both any PDA and hsPDA (Table 1). For both meta-analyses, the RoBMA did not find evidence in favour of publication bias (Any PDA: BFbias = 0.49; hsPDA: BFbias = 0.33, Supplementary Table S3).
Sixteen studies reported the mean or median GA of infants exposed and unexposed to HDP during gestation [27,30,35,37,38,42,44,48,50,54,55,56,57,61,63]. Infants exposed to HDP had a GA at birth 0.97 weeks higher (Standard error = 0.16) than unexposed infants. This difference corresponds to a value of Hedges’ g of 0.44 (95% CrI 0.28 to 0.60). BMA analysis showed that the evidence in favour of this higher GA in the HDP-exposed group was extreme (BF10 = 2498).

3.3. Subgroup Analysis and Meta-Regression

Subgroup analyses based on the subtype of HDP showed that the moderate evidence in favour of H0 was only present for the associations of any PDA with preeclampsia (BF10 = 0.30, Table 1, Figure 2) and hsPDA with preeclampsia (BF10 = 0.17, Table 1, Figure 3). For the other HDP subtypes, the BMA analysis showed weak evidence in favour of H0 (Table 1).
Meta-regression showed that the differences in GA between the infants exposed or unexposed to HDP in each individual study correlated with the effect size (logOR) of the association between HDP and hsPDA (seven studies; standardized meta-regression coefficient: −0.20, 95% CrI −0.34 to 0.02; BFmod = 5.75), but not with the effect size of the association between HDP and any PDA (nine studies; meta-regression coefficient: 0.03, 95% CrI −0.20 to 0.26; BFmod = 0.86) (Figure 4, Supplementary Table S4).

4. Discussion

To the best of our knowledge, this study represents the most comprehensive examination of the potential association between HDP and PDA in infants with GA ≤ 32 weeks. A broad search strategy has enabled the inclusion of a greater number of studies than those included in previous meta-analyses. Moreover, the application of a Bayesian approach has facilitated the drawing of more nuanced conclusions. A frequentist approach would have led to the conclusion that no statistically significant association was found between HDP and any PDA (p = 0.514) or hsPDA (p = 0.348). However, it would not have been possible to ascertain whether these findings provided evidence of no association (H0 should be accepted) or indicated an absence of evidence (the data are inconclusive to accept or reject H0). Bayesian hypothesis testing aims to quantify the relative plausibility of H1 and H0. Thus, the Bayesian approach allows us to estimate that the observed data are five times (BF10 = 0.20; BF01 = 5.00) more likely under no association (H0) between HDP and any PDA than under the presence of association (H1). Similarly, the observed data are 3.7 times (BF10 = 0.27; BF01 = 3.70) more likely under no association between HDP and hsPDA than under the presence of association. We can therefore conclude that there is moderate evidence for an absence of association between HDP and both any PDA and hsPDA.
Adverse prenatal conditions may have a profound effect in foetal development as well as in the clinical outcome of preterm infants. It is therefore biologically plausible that HDP may affect ductal development, resulting in an altered risk of PDA. Of note, a number of population-based studies have demonstrated an association between early-onset preeclampsia (<34 weeks of gestation) and congenital cardiac defects in offspring [65,66]. These defects may affect all general structures of the heart, including the aorta, pulmonary artery, valves, ventricles, and septa [65,66]. The proposed mechanism for this association is the effect on cardiovascular development of the imbalances in proangiogenic signalling proteins, such as vascular endothelial growth factor and placental growth factor, and antiangiogenic proteins, such as soluble endoglin and fms-like tyrosine kinase 1 [65,66,67,68]. This angiogenic imbalance may be involved in the pathophysiology of preeclampsia as well as in the pathogenesis of congenital heart defects [65,66,67,68]. Interestingly, PDA in term newborns is one of the conditions that has been associated with early-onset preeclampsia [65]. However, the etiopathogenic mechanisms underlying PDA in term and preterm newborns are distinct. In term and late-preterm infants, PDA is a relatively uncommon condition that is often associated with intrinsic abnormalities of the DA and/or signalling pathways that normally trigger its closure [69,70]. In contrast, PDA in very preterm infants is mainly due to developmental immaturity. Therefore, PDA would likely not be present if the infant had been born at term [69,70].
The main limitation of our meta-analysis was the high heterogeneity. To identify the potential sources of this heterogeneity, we conducted subgroup analysis and meta-regression. The subgroup analysis focused on the various definitions of HDP, whereas the meta-regression analysed the potential moderating effect of the differences in GA between infants exposed and unexposed to HDP in each individual study. We observed that the absence of an association between HDP and the risk of developing PDA was mainly evident for preeclampsia. In contrast, a previous meta-analysis by our group showed that infants with a history of preeclampsia had higher rates of pharmacological PDA closure compared with those with a history of chorioamnionitis or growth retardation [9]. However, it is important to acknowledge that any investigation into the potential associations between the pathophysiological conditions, or endotypes, that trigger preterm birth and the outcome of prematurity is constrained by the absence of a ‘healthy’ control group. Extremely preterm birth is, by definition, a pathological condition. The healthy control would be a foetus of a similar GA that is still in the womb in physiological conditions. Furthermore, as demonstrated in the present and previous meta-analyses, preterm infants exposed to HDP tend to have a higher GA than those unexposed [9,11,12]. This results in higher clinical stability and lower incidence of respiratory complications, which may play a role in both spontaneous and pharmacologic ductal closure [9,11,12].
Low GA is the main risk factor for developing PDA [1,2,3,4]. Therefore, it is noteworthy that infants exposed to HDP, who tend to have a higher GA than unexposed infants, do not have a lower risk of developing PDA. In contrast, as evidenced by previous meta-analyses, very/extremely preterm infants exposed to HDP have a reduced risk of mortality and BPD [11,12]. At least a part of this reduced risk can be attributed to the higher GA of HDP-exposed infants [11,12]. Of note, this lower risk of mortality and BPD evolves into a higher risk when the placental dysfunction endotype is represented by growth retardation instead of HDP [11,12]. In the case of PDA, it can be speculated that the potential pathological effect of HDP on ductal development is counterbalanced or masked by the higher degree of maturation (i.e., higher GA) of the HDP-exposed infants. Thus, a higher GA may independently reduce the risk of PDA and counteract any HDP-related effects. In fact, the meta-regression analysis showed a correlation between the effect size of the association between hsPDA and BPD and the difference in GA between the HDP-exposed and control groups. However, this meta-regression is constrained by the limited number of studies that could be included. GA data for the HDP-exposed and non-exposed groups were only available in 16 studies [27,30,35,37,38,42,44,48,50,54,55,56,57,61,63]. These studies reported various outcomes, including PDA, for HDP-exposed and non-exposed infants. The remaining studies reported different risk factors for developing PDA and therefore provided GA data for infants with and without PDA.
While publication bias is a recognized issue in both randomized controlled trials and observational studies, systematic reviews have consistently shown that the risk is higher in observational research [71,72]. This is likely due to less stringent requirements for protocol registration and reporting standards in observational studies, as well as greater variability in study designs and outcomes, which can facilitate selective publication of positive findings [71,72]. Although our research question could only be addressed by observational studies, the RoBMA analysis showed no evidence in favour of the presence of publication bias in any of the meta-analyses.
Finally, the variability in the definitions of both exposures and outcomes is a substantial limitation of meta-analyses of observational studies. Despite the periodic publication of consensus documents on the classification and diagnostic criteria for HDP, there may be differences among physicians regarding the application of these criteria [73]. Furthermore, our study does not consider the degree of severity or the duration of exposure to HDP prior to birth. It is noteworthy that our previous meta-analysis demonstrated that when placental dysfunction was severe enough to induce growth retardation, there was an increased risk of developing PDA [13]. With regard to the definition of PDA, there is considerable variation in the criteria used to determine when a PDA is hemodynamically significant [4]. However, our analysis shows that the absence of an association with HDP was present for both PDA and hsPDA.

5. Conclusions

In conclusion, our meta-analysis shows moderate evidence for the absence of an association between HDP, particularly preeclampsia, and the risk of developing PDA. However, part of this effect may be modulated by the fact that preterm infants exposed to HDP during gestation have higher GAs. In view of the potential importance of antenatal pathological conditions for the personalised clinical care of extremely preterm newborns, it is necessary to integrate the antenatal history and placental pathology into the clinical decision-making process.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/children12060762/s1, Search strategy; Table S1: Characteristics of the included studies and risk of bias assessment; Table S2: Data on heterogeneity of the Bayesian model-averaged meta-analysis of the association between hypertensive disorders of pregnancy and patent ductus arteriosus in preterm infants; Table S3: Robust Bayesian meta-analysis (RoBMA) of the association between hypertensive disorders of pregnancy and patent ductus arteriosus in preterm infants; Table S4: Bayesian model-averaged meta-regression (BMA-reg) of moderating effect of the difference in GA (mean GA of HDP-exposed group minus mean GA of non-exposed group of each individual study) on the association between hypertensive disorders of pregnancy and patent ductus arteriosus in preterm infants.

Author Contributions

E.V. conceived and designed the study, with input from the other authors. E.V. and G.E.G.-L. executed the literature search. M.B.-L., G.G.-H. and R.I.R.-V. abstracted the data and assessed the quality of the included studies. E.V. and G.E.G.-L. checked data extraction for accuracy and completeness. F.B. designed and conducted the Bayesian analysis with input from E.V. All authors contributed to the interpretation of analyses. M.B.-L. and E.V. made the figures and tables. M.B.-L. and E.V. drafted the manuscript with input from the other authors. All authors reviewed the manuscript and provided important intellectual content. E.V. and G.E.G.-L. take responsibility for the article as a whole. All authors have read and agreed to the published version of the manuscript.

Funding

This research was partially funded by Fundación Canaria Colegio de Médicos de Las Palmas, Grant No. 26/2021.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

All data relevant to the study are included in the article or uploaded as Supplementary Information.

Acknowledgments

We would like to thank Ana Martinez-Olaizola for technical and administrative support.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
BFBayes factor
BMABayesian model-averaged
CIConfidence interval
CrICredible interval
DADuctus arteriosus
GAGestational age
HDPHypertensive disorders of pregnancy
H0Null hypothesis
H1Alternative hypothesis
OROdds ratio
PDAPatent ductus arteriosus

References

  1. Reese, J.; Laughon, M.M. The patent ductus arteriosus problem: Infants who still need treatment. J. Pediatr. 2015, 167, 954–956. [Google Scholar] [CrossRef] [PubMed]
  2. Gillam-Krakauer, M.; Reese, J. Diagnosis and management of patent ductus arteriosus. Neoreviews 2018, 19, e394–e402. [Google Scholar] [CrossRef] [PubMed]
  3. Deshpande, P.; Baczynski, M.; McNamara, P.J.; Jain, A. (Eds.) Patent ductus arteriosus: The physiology of transition. In Seminars in Fetal and Neonatal Medicine; Elsevier: Amsterdam, The Netherlands, 2018. [Google Scholar] [CrossRef]
  4. Hamrick, S.E.; Sallmon, H.; Rose, A.T.; Porras, D.; Shelton, E.L.; Reese, J.; Hansmann, G. Patent ductus arteriosus of the preterm infant. Pediatrics 2020, 146, e20201209. [Google Scholar] [CrossRef] [PubMed]
  5. Agache, I.; Akdis, C.A. Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases. J. Clin. Investig. 2019, 129, 1493–1503. [Google Scholar] [CrossRef]
  6. Lötvall, J.; Akdis, C.A.; Bacharier, L.B.; Bjermer, L.; Casale, T.B.; Custovic, A.; Lemanske, R.F.L., Jr.; Wardlaw, A.J.; Wenzel, S.E.; Greenberger, P.A. Asthma endotypes: A new approach to classification of disease entities within the asthma syndrome. J. Allergy Clin. Immunol. 2011, 127, 355–360. [Google Scholar] [CrossRef]
  7. McElrath, T.F.; Hecht, J.L.; Dammann, O.; Boggess, K.; Onderdonk, A.; Markenson, G.; Harper, M.; Delpapa, E.; Allred, E.N.; Leviton, A.; et al. Pregnancy disorders that lead to delivery before the 28th week of gestation: An epidemiologic approach to classification. Am. J. Epidemiol. 2008, 168, 980–989. [Google Scholar] [CrossRef]
  8. Villamor, E.; Borges-Luján, M.; González-Luis, G. (Eds.) Association of patent ductus arteriosus with fetal factors and endotypes of prematurity. In Seminars in Perinatology; Elsevier: Amsterdam, The Netherlands, 2023. [Google Scholar] [CrossRef]
  9. Gonzalez-Luis, G.E.; Borges-Lujan, M.; Villamor, E. Association between endotypes of prematurity and pharmacological closure of patent ductus arteriosus: A systematic review and meta-analysis. Front. Pediatr. 2023, 11, 1078506. [Google Scholar] [CrossRef]
  10. Behbodi, E.; Villamor-Martínez, E.; Degraeuwe, P.L.; Villamor, E. Chorioamnionitis appears not to be a risk factor for patent ductus arteriosus in preterm infants: A systematic review and meta-analysis. Sci. Rep. 2016, 6, 37967. [Google Scholar] [CrossRef]
  11. Hundscheid, T.M.; Villamor-Martinez, E.; Villamor, E. Association between endotype of prematurity and mortality: A systematic review, meta-analysis, and meta-regression. Neonatology 2023, 120, 407–416. [Google Scholar] [CrossRef]
  12. Pierro, M.; Villamor-Martinez, E.; van Westering-Kroon, E.; Alvarez-Fuente, M.; Abman, S.H.; Villamor, E. Association of the dysfunctional placentation endotype of prematurity with bronchopulmonary dysplasia: A systematic review, meta-analysis and meta-regression. Thorax 2022, 77, 268–275. [Google Scholar] [CrossRef]
  13. Villamor-Martinez, E.; Kilani, M.A.; Degraeuwe, P.L.; Clyman, R.I.; Villamor, E. Intrauterine growth restriction and patent ductus arteriosus in very and extremely preterm infants: A systematic review and meta-analysis. Front. Endocrinol. 2019, 10, 58. [Google Scholar] [CrossRef] [PubMed]
  14. Magee, L.A.; Von Dadelszen, P. (Eds.) State-of-the-art diagnosis and treatment of hypertension in pregnancy. In Mayo Clinic Proceedings; Elsevier: Amsterdam, The Netherlands, 2018. [Google Scholar] [CrossRef]
  15. Liu, C.; Zhu, X.; Li, D.; Shi, Y. Related factors of patent ductus arteriosus in preterm infants: A systematic review and meta-analysis. Front. Pediatr. 2021, 8, 605879. [Google Scholar] [CrossRef]
  16. Wijeysundera, D.N.; Austin, P.C.; Hux, J.E.; Beattie, W.S.; Laupacis, A. Bayesian statistical inference enhances the interpretation of contemporary randomized controlled trials. J. Clin. Epidemiol. 2009, 62, 13–21.e5. [Google Scholar] [CrossRef] [PubMed]
  17. Stang, A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur. J. Epidemiol. 2010, 25, 603–605. [Google Scholar] [CrossRef]
  18. Bartoš, F.; Gronau, Q.F.; Timmers, B.; Otte, W.M.; Ly, A.; Wagenmakers, E.J. Bayesian model-averaged meta-analysis in medicine. Stat. Med. 2021, 40, 6743–6761. [Google Scholar] [CrossRef]
  19. Gronau, Q.F.; Heck, D.W.; Berkhout, S.W.; Haaf, J.M.; Wagenmakers, E.-J. A primer on Bayesian model-averaged meta-analysis. Adv. Methods Pract. Psychol. Sci. 2021, 4, 25152459211031256. [Google Scholar] [CrossRef]
  20. van Doorn, J.; van den Bergh, D.; Böhm, U.; Dablander, F.; Derks, K.; Draws, T.; Etz, A.; Evans, N.J.; Gronau, Q.F.; Haaf, J.M.; et al. The JASP guidelines for conducting and reporting a Bayesian analysis. Psychon. Bull. Rev. 2021, 28, 813–826. [Google Scholar] [CrossRef] [PubMed]
  21. Lee, M.; Wagenmakers, E.-J. Bayesian Data Analysis for Cognitive Science: A Practical Course; Cambridge University Press: New York, NY, USA, 2013. [Google Scholar]
  22. Bartoš, F.; Maier, M.; Wagenmakers, E.J.; Doucouliagos, H.; Stanley, T. Robust Bayesian meta-analysis: Model-averaging across complementary publication bias adjustment methods. Res. Synth. Methods 2023, 14, 99–116. [Google Scholar] [CrossRef]
  23. Bartoš, F.; Maier, M.; Stanley, T.; Wagenmakers, E.-J. Robust Bayesian Meta-Regression—Model-Averaged Moderation Analysis in the Presence of Publication Bias. Psychol. Methods, 2023; ahead of print. [Google Scholar] [CrossRef]
  24. Ahmed, E.G.; Samra, N.M.; Amin, S.A.; Borayek, H.A.; Abdelrazek, G. Platelets and platelet derived growth factor and ductus arteriosus in preterm neonates. Prog. Pediatr. Cardiol. 2020, 57, 101226. [Google Scholar] [CrossRef]
  25. Akar, S.; Topcuoglu, S.; Tuten, A.; Ozalkaya, E.; Karatepe, H.O.; Gokmen, T.; Ovali, F.; Karatekin, G. Is the First Postnatal Platelet Mass as an Indicator of Patent Ductus Arteriosus? Arch. Iran. Med. 2019, 22, 687. [Google Scholar] [PubMed]
  26. Bas-Suárez, M.P.; González-Luis, G.E.; Saavedra, P.; Villamor, E. Platelet counts in the first seven days of life and patent ductus arteriosus in preterm very low-birth-weight infants. Neonatology 2014, 106, 188–194. [Google Scholar] [CrossRef] [PubMed]
  27. Bossung, V.; Fortmann, M.I.; Fusch, C.; Rausch, T.; Herting, E.; Swoboda, I.; Rody, A.; Härtel, C.; Göpel, W.; Humberg, A. Neonatal outcome after preeclampsia and HELLP syndrome: A population-based cohort study in Germany. Front. Pediatr. 2020, 8, 579293. [Google Scholar] [CrossRef] [PubMed]
  28. Brunner, B.; Hoeck, M.; Schermer, E.; Streif, W.; Kiechl-Kohlendorfer, U. Patent ductus arteriosus, low platelets, cyclooxygenase inhibitors, and intraventricular hemorrhage in very low birth weight preterm infants. J. Pediatr. 2013, 163, 23–28. [Google Scholar] [CrossRef]
  29. Clyman, R.I.; Hills, N.K. The effect of prolonged tracheal intubation on the association between patent ductus arteriosus and bronchopulmonary dysplasia (grades 2 and 3). J. Perinatol. 2020, 40, 1358–1365. [Google Scholar] [CrossRef] [PubMed]
  30. de Souza Rugolo, L.M.S.; de Sá, M.P.A.; Kurokawa, C.S.; Madoglio, R.J.; Bentlin, M.R.; Rugolo, A., Jr.; Corrente, J.E. There is no difference in nitric oxide metabolites and neonatal outcome between premature infants born to pre-eclamptic and those born to normotensive women. Paediatr. Int. Child Health 2015, 35, 47–52. [Google Scholar] [CrossRef]
  31. Demir, N.; Peker, E.; Ece, İ.; Ağengin, K.; Bulan, K.A.; Tuncer, O. Is platelet mass a more significant indicator than platelet count of closure of patent ductus arteriosus? J. Matern. Fetal Neonatal Med. 2016, 29, 1915–1918. [Google Scholar] [CrossRef]
  32. Dizdar, A.E.; Ozdemir, R.; Nur Sari, F.; Yurttutan, S.; Gokmen, T.; Erdeve, O.; Canpolat, F.E.; Uras, N.; Oguz, S.S.; Dilmen, U. Low platelet count is associated with ductus arteriosus patency in preterm newborns. Early Hum. Dev. 2012, 88, 813–816. [Google Scholar] [CrossRef]
  33. Echtler, K.; Stark, K.; Lorenz, M.; Kerstan, S.; Walch, A.; Jennen, L.; Rudelius, M.; Seidl, S.; Kremmer, E.; Emambokus, N.R.; et al. Platelets contribute to postnatal occlusion of the ductus arteriosus. Nat. Med. 2010, 16, 75–82. [Google Scholar] [CrossRef]
  34. El-Khuffash, A.F.; Molloy, E.J. Influence of a patent ductus arteriosus on cardiac troponin T levels in preterm infants. J. Pediatr. 2008, 153, 350–353. [Google Scholar] [CrossRef]
  35. Gray, P.H.; Hurley, T.M.; Rogers, Y.M.; O’Callaghan, M.J.; Tudehope, D.I.; Burns, Y.R.; Phty, M.; Mohay, H.A. Survival and neonatal and neurodevelopmental outcome of 24–29 week gestation infants according to primary cause of preterm delivery. Aust. N. Z. J. Obstet. Gynaecol. 1997, 37, 161–168. [Google Scholar] [CrossRef]
  36. Hammoud, M.S.; Elsori, H.A.; Hanafi, E.A.; Shalabi, A.A.; Fouda, I.A.; Devarajan, L.V. Incidence and risk factors associated with the patency of ductus arteriosus in preterm infants with respiratory distress syndrome in Kuwait. Saudi Med. J. 2003, 24, 982–985. [Google Scholar] [PubMed]
  37. Hentges, C.R.; Silveira, R.C.; Procianoy, R.S. Angiogenic and antiangiogenic factors in preterm neonates born to mothers with and without preeclampsia. Am. J. Perinatol. 2015, 32, 1185–1190. [Google Scholar] [CrossRef]
  38. Huang, H.-C.; Yang, H.-I.; Chou, H.-C.; Chen, C.-Y.; Hsieh, W.-S.; Tsou, K.-I.; Tsao, P.-N.; Taiwan Premature Infant Developmental Collaborative Study Group. Preeclampsia and retinopathy of prematurity in very-low-birth-weight infants: A population-based study. PLoS ONE 2015, 10, e0143248. [Google Scholar] [CrossRef]
  39. Inayat, M.; Bany-Mohammed, F.; Valencia, A.; Tay, C.; Jacinto, J.; Aranda, J.V.; Beharry, K.D. Antioxidants and biomarkers of oxidative stress in preterm infants with symptomatic patent ductus arteriosus. Am. J. Perinatol. 2015, 32, 895–904. [Google Scholar] [CrossRef]
  40. Janz-Robinson, E.M.; Badawi, N.; Walker, K.; Bajuk, B.; Abdel-Latif, M.E.; Bowen, J.; Sedgley, S.; Carlisle, H.; Smith, J.; Craven, P.; et al. Neurodevelopmental outcomes of premature infants treated for patent ductus arteriosus: A population-based cohort study. J. Pediatr. 2015, 167, 1025–1032.e3. [Google Scholar] [CrossRef]
  41. Katheria, V.; Poeltler, D.; Brown, M.; Hassen, K.; Patel, D.; Rich, W.; Finer, N.; Katheria, A. Early prediction of a significant patent ductus arteriosus in infants < 32 weeks gestational age. J. Neonatal Perinat. Med. 2018, 11, 265–271. [Google Scholar] [CrossRef]
  42. Kim, D.-H.; Shin, S.H.; Kim, E.-K.; Kim, H.-S. Association of increased cord blood soluble endoglin with the development of bronchopulmonary dysplasia in preterm infants with maternal preeclampsia. Pregnancy Hypertens. 2018, 13, 148–153. [Google Scholar] [CrossRef]
  43. Lee, J.A.; Sohn, J.A.; Oh, S.; Choi, B.M. Perinatal risk factors of symptomatic preterm patent ductus arteriosus and secondary ligation. Pediatr. Neonatol. 2020, 61, 439–446. [Google Scholar] [CrossRef] [PubMed]
  44. Matić, M.; Inati, V.; Abdel-Latif, M.E.; Kent, A.L.; Network, N.A.N. Maternal hypertensive disorders are associated with increased use of respiratory support but not chronic lung disease or poorer neurodevelopmental outcomes in preterm neonates at <29 weeks of gestation. J. Paediatr. Child. Health. 2017, 53, 391–398. [Google Scholar] [CrossRef]
  45. Oliveira, A.; Soares, P.; Flor-de-Lima, F.; Neves, A.L.; Guimarães, H. PDA management in VLBW infants: Experience of a level III NICU. J. Pediatr. Neonatal Individ. Med. 2016, 5, e050227. [Google Scholar] [CrossRef]
  46. Olukman, O.; Ozdemir, R.; Karadeniz, C.; Calkavur, S.; Mese, T.; Vergin, C. Is there a relationship between platelet parameters and patency of ductus arteriosus in preterm infants? Blood Coagul. Fibrinolysis 2017, 28, 8–13. [Google Scholar] [CrossRef]
  47. Patole, S.K.; Kumaran, V.; Travadi, J.N.; Brooks, J.M.; Doherty, D.A. Does patent ductus arteriosus affect feed tolerance in preterm neonates? Arch. Dis. Child. Fetal Neonatal Ed. 2007, 92, F53–F55. [Google Scholar] [CrossRef]
  48. Rocha, G.; de Lima, F.F.; Machado, A.P.; Guimaraes, H. Preeclampsia predicts higher incidence of bronchopulmonary dysplasia. J. Perinatol. 2018, 38, 1165–1173. [Google Scholar] [CrossRef]
  49. Romagnoli, V.; Pedini, A.; Santoni, M.; Scutti, G.; Colaneri, M.; Pozzi, M.; Cogo, P.E.; Carnielli, V.P. Patent ductus arteriosus in preterm infants born before 30 weeks’ gestation: High rate of spontaneous closure after hospital discharge. Cardiol. Young 2018, 28, 995–1000. [Google Scholar] [CrossRef] [PubMed]
  50. Schlapbach, L.J.; Ersch, J.; Adams, M.; Bernet, V.; Bucher, H.U.; Latal, B. Impact of chorioamnionitis and preeclampsia on neurodevelopmental outcome in preterm infants below 32 weeks gestational age. Acta Paediatr. 2010, 99, 1504–1509. [Google Scholar] [CrossRef] [PubMed]
  51. Sellmer, A.; Bjerre, J.V.; Schmidt, M.R.; McNamara, P.J.; Hjortdal, V.E.; Høst, B.; Bech, B.H.; Henriksen, T.B. Morbidity and mortality in preterm neonates with patent ductus arteriosus on day 3. Arch. Dis. Child. Fetal Neonatal Ed. 2013, 98, F505–F510. [Google Scholar] [CrossRef] [PubMed]
  52. Shah, N.A.; Hills, N.K.; Waleh, N.; McCurnin, D.; Seidner, S.; Chemtob, S.; Clyman, R. Relationship between circulating platelet counts and ductus arteriosus patency after indomethacin treatment. J. Pediatr. 2011, 158, 919–923.e2. [Google Scholar] [CrossRef]
  53. Shekharappa, C.B.; Elizabeth, E.A.B.; Balachander, B. Association of patent ductus arteriosus size with clinical features and short-term outcomes in preterm infants less than 34 weeks. Indian J. Child Health. 2020, 105–108. [Google Scholar] [CrossRef]
  54. Soliman, N.; Chaput, K.; Alshaikh, B.; Yusuf, K. Preeclampsia and the risk of bronchopulmonary dysplasia in preterm infants less than 32 weeks’ gestation. Am. J. Perinatol. 2017, 34, 585–592. [Google Scholar] [CrossRef]
  55. Su, Z.; Huang, W.; Meng, Q.; Jia, C.; Shi, B.; Fan, X.; Cui, Q.; Chen, J.; Wu, F. Mothers with hypertensive disorders of pregnancy increased risk of periventricular leukomalacia in extremely preterm or extremely low birth weight infants: A propensity score analysis. Front. Pediatr. 2022, 10, 978373. [Google Scholar] [CrossRef]
  56. Tokumasu, H.; Tokumasu, S.; Kawakami, K. Impact of pre-eclampsia in extremely premature infants: Population-based study. Pediatr. Int. 2016, 58, 578–583. [Google Scholar] [CrossRef] [PubMed]
  57. Turunen, R.; Andersson, S.; Laivuori, H.; Kajantie, E.; Siitonen, S.; Repo, H.; Nupponen, I. Increased postnatal inflammation in mechanically ventilated preterm infants born to mothers with early-onset preeclampsia. Neonatology 2011, 100, 241–247. [Google Scholar] [CrossRef]
  58. van de Bor, M.; Verloove-Vanhorick, S.P.; Brand, R.; Ruys, J.H. Patent ductus arteriosus in a cohort of 1338 preterm infants: A collaborative study. Paediatr. Perinat. Epidemiol. 1988, 2, 328–336. [Google Scholar] [CrossRef]
  59. Velazquez, D.M.; Reidy, K.J.; Sharma, M.; Kim, M.; Vega, M.; Havranek, T. The effect of hemodynamically significant patent ductus arteriosus on acute kidney injury and systemic hypertension in extremely low gestational age newborns. J. Matern. Fetal Neonatal Med. 2019, 32, 3209–3214. [Google Scholar] [CrossRef]
  60. Vieux, R.; Desandes, R.; Boubred, F.; Semama, D.; Guillemin, F.; Buchweiller, M.-C.; Fresson, J.; Hascoet, J.-M. Ibuprofen in very preterm infants impairs renal function for the first month of life. Pediatr. Nephrol. 2010, 25, 267–274. [Google Scholar] [CrossRef]
  61. Withagen, M.I.; Visser, W.; Wallenburg, H.C. Neonatal outcome of temporizing treatment in early-onset preeclampsia. Eur. J. Obstet. Gynecol. Reprod. Biol. 2001, 94, 211–215. [Google Scholar] [CrossRef] [PubMed]
  62. Yen, T.-A.; Yang, H.-I.; Hsieh, W.-S.; Chou, H.-C.; Chen, C.-Y.; Tsou, K.-I.; Tsao, P.-N.; for the Taiwan Premature Infant Developmental Collaborative Study Group. Preeclampsia and the risk of bronchopulmonary dysplasia in VLBW infants: A population-based study. PLoS ONE 2013, 8, e75168. [Google Scholar] [CrossRef] [PubMed]
  63. Yılmaz, Y.; Kutman, H.G.K.; Ulu, H.Ö.; Canpolat, F.E.; Uraş, N.; Oğuz, S.S.; Dilmen, U. Preeclampsia is an independent risk factor for spontaneous intestinal perforation in very preterm infants. J. Matern. Fetal Neonatal Med. 2014, 27, 1248–1251. [Google Scholar] [CrossRef]
  64. Yum, S.K.; Moon, C.-J.; Youn, Y.-A.; Lee, J.Y.; Sung, I.K. Echocardiographic assessment of patent ductus arteriosus in very low birthweight infants over time: Prospective observational study. J. Matern. Fetal Neonatal Med. 2018, 31, 164–172. [Google Scholar] [CrossRef]
  65. Auger, N.; Fraser, W.D.; Healy-Profitós, J.; Arbour, L. Association between preeclampsia and congenital heart defects. JAMA 2015, 314, 1588–1598. [Google Scholar] [CrossRef]
  66. Boyd, H.A.; Basit, S.; Behrens, I.; Leirgul, E.; Bundgaard, H.; Wohlfahrt, J.; Melbye, M.; Øyen, N. Association between fetal congenital heart defects and maternal risk of hypertensive disorders of pregnancy in the same pregnancy and across pregnancies. Circulation 2017, 136, 39–48. [Google Scholar] [CrossRef] [PubMed]
  67. Sliwa, K.; Mebazaa, A. Possible joint pathways of early pre-eclampsia and congenital heart defects via angiogenic imbalance and potential evidence for cardio-placental syndrome. Eur. Heart J. 2014, 35, 680–682. [Google Scholar] [CrossRef] [PubMed]
  68. Llurba, E.; Sanchez, O.; Ferrer, Q.; Nicolaides, K.H.; Ruíz, A.; Domínguez, C.; Sánchez-De-Toledo, J.; García-García, B.; Soro, G.; Arévalo, S.; et al. Maternal and foetal angiogenic imbalance in congenital heart defects. Eur. Heart J. 2014, 35, 701–707. [Google Scholar] [CrossRef]
  69. Hajj, H.; Dagle, J.M. Genetics of patent ductus arteriosus susceptibility and treatment. Semin. Perinatol. 2012, 36, 96–104. [Google Scholar] [CrossRef]
  70. Schneider, D.J. The patent ductus arteriosus in term infants, children, and adults. Semin. Perinatol. 2012, 36, 146–153. [Google Scholar] [CrossRef]
  71. Easterbrook, P.J.; Gopalan, R.; Berlin, J.; Matthews, D.R. Publication bias in clinical research. Lancet 1991, 337, 867–872. [Google Scholar] [CrossRef] [PubMed]
  72. Dwan, K.; Altman, D.G.; Arnaiz, J.A.; Bloom, J.; Chan, A.-W.; Cronin, E.; Decullier, E.; Easterbrook, P.J.; Von Elm, E.; Gamble, C. Systematic review of the empirical evidence of study publication bias and outcome reporting bias. PLoS ONE 2008, 3, e3081. [Google Scholar] [CrossRef]
  73. Lai, J.; Syngelaki, A.; Nicolaides, K.H.; von Dadelszen, P.; Magee, L.A. Impact of new definitions of preeclampsia at term on identification of adverse maternal and perinatal outcomes. Am. J. Obstet. Gynecol. 2021, 224, 518.e1–e11. [Google Scholar] [CrossRef]
Children 12 00762 g001
Figure 1. Flow diagram of the systematic search.
Figure 1. Flow diagram of the systematic search.
Children 12 00762 g001
Children 12 00762 g002
Figure 2. Bayesian model-averaged (BMA) meta-analysis of the association between hypertensive disorders of pregnancy and any patent ductus arteriosus in preterm infants [24,27,28,30,35,37,42,43,45,47,49,51,52,54,57,61,63].
Figure 2. Bayesian model-averaged (BMA) meta-analysis of the association between hypertensive disorders of pregnancy and any patent ductus arteriosus in preterm infants [24,27,28,30,35,37,42,43,45,47,49,51,52,54,57,61,63].
Children 12 00762 g002
Children 12 00762 g003
Figure 3. Bayesian model-averaged (BMA) meta-analysis of the association between hypertensive disorders of pregnancy and hemodynamically significant patent ductus arteriosus in preterm infants [25,26,29,31,32,33,34,36,38,39,40,41,44,46,47,48,50,53,55,56,58,59,60,62,64].
Figure 3. Bayesian model-averaged (BMA) meta-analysis of the association between hypertensive disorders of pregnancy and hemodynamically significant patent ductus arteriosus in preterm infants [25,26,29,31,32,33,34,36,38,39,40,41,44,46,47,48,50,53,55,56,58,59,60,62,64].
Children 12 00762 g003
Children 12 00762 g004
Figure 4. Bayesian model-averaged meta-regression (BMA-reg). Meta-regression plot showing the correlation between the effect size (log OR) of the association between hypertensive disorders of pregnancy and (A) any patent ductus arteriosus and (B) hemodynamically significant ductus arteriosus and the difference in gestational age (GA, exposed minus unexposed group in each individual study). The size of the circles is proportional to the contribution of each individual study to the association.
Figure 4. Bayesian model-averaged meta-regression (BMA-reg). Meta-regression plot showing the correlation between the effect size (log OR) of the association between hypertensive disorders of pregnancy and (A) any patent ductus arteriosus and (B) hemodynamically significant ductus arteriosus and the difference in gestational age (GA, exposed minus unexposed group in each individual study). The size of the circles is proportional to the contribution of each individual study to the association.
Children 12 00762 g004
Table 1. Bayesian model-averaged (BMA) meta-analysis of the association between hypertensive disorders of pregnancy and any patent ductus arteriosus in preterm infants.
Table 1. Bayesian model-averaged (BMA) meta-analysis of the association between hypertensive disorders of pregnancy and any patent ductus arteriosus in preterm infants.
OutcomeSubgroupKOR95% Credible IntervalBF10Evidence forp-Value aBFrf
Lower
Limit		Upper LimitH1H0
Any PDAAll171.060.781.420.20 Mod.0.514>107
Any HDP51.200.702.010.44 Weak0.52460.89
Preeclampsia70.840.511.370.30 Mod.0.60521.94
Preeclampsia/HELLP51.190.702.030.39 Weak0.543>103
Hemodynamically significant PDAAll250.890.741.080.27 Mod.0.348>106
Any HDP80.840.621.120.45 Weak0.3164.56
Preeclampsia150.950.731.260.17 Mod.0.401>105
Preeclampsia/HELLP20.670.351.711.20Weak 0.6032.15
a p-value of random effects frequentist meta-analysis. BF: Bayes factor; HDP: hypertensive disorders of pregnancy; K: number of studies; Mod.: Moderate; OR: odds ratio; PDA: patent ductus arteriosus. The BF10 is the ratio of the probability of the data under H1 over the probability of the data under H0. Moderate evidence for H0 = BF10 from 1/10 to <1/3; weak/inconclusive evidence for H0 = BF10 from 1/3 to <1; weak/inconclusive evidence for H1 = BF10 from 1 to 3. The BFrf is the ratio of the probability of the data under the random-effects model over the probability of the data under the fixed-effects model.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Borges-Luján, M.; Galán-Henríquez, G.; Rodríguez-Viera, R.I.; Bartoš, F.; González-Luis, G.E.; Villamor, E. Association Between Hypertensive Disorders of Pregnancy and Patent Ductus Arteriosus in Very Preterm Infants: A Bayesian Model-Averaged Meta-Analysis. Children 2025, 12, 762. https://doi.org/10.3390/children12060762

AMA Style

Borges-Luján M, Galán-Henríquez G, Rodríguez-Viera RI, Bartoš F, González-Luis GE, Villamor E. Association Between Hypertensive Disorders of Pregnancy and Patent Ductus Arteriosus in Very Preterm Infants: A Bayesian Model-Averaged Meta-Analysis. Children. 2025; 12(6):762. https://doi.org/10.3390/children12060762

Chicago/Turabian Style

Borges-Luján, Moreyba, Gloria Galán-Henríquez, Rosa I. Rodríguez-Viera, František Bartoš, Gema E. González-Luis, and Eduardo Villamor. 2025. "Association Between Hypertensive Disorders of Pregnancy and Patent Ductus Arteriosus in Very Preterm Infants: A Bayesian Model-Averaged Meta-Analysis" Children 12, no. 6: 762. https://doi.org/10.3390/children12060762

APA Style

Borges-Luján, M., Galán-Henríquez, G., Rodríguez-Viera, R. I., Bartoš, F., González-Luis, G. E., & Villamor, E. (2025). Association Between Hypertensive Disorders of Pregnancy and Patent Ductus Arteriosus in Very Preterm Infants: A Bayesian Model-Averaged Meta-Analysis. Children, 12(6), 762. https://doi.org/10.3390/children12060762

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop