OBJECTIVE: To examine the association between enteral supplementation with high-dose DHA during the neonatal period and the risk of BPD in preterm infants born at less than 29 weeks' gestation.

DATA SOURCES: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, medRxiv, and ClinicalTrials.gov were searched from inception to August 1, 2022, for eligible articles with no language restrictions.

STUDY SELECTION: Randomized clinical trials (RCTs) were eligible for inclusion (1) if their interventions involved direct administration of a minimum DHA supplementation of 40 mg/kg/d or breast milk or formula feeding of at least 0.4% of total fatty acids, and (2) if they reported data on either BPD, death, BPD severity, or a combined outcome of BPD and death.

DATA EXTRACTION AND SYNTHESIS: Two investigators completed independent review of titles and abstracts, full text screening, data extraction, and quality assessment using the Cochrane Risk of Bias 2.0. Risk ratios (RRs) with 95% CIs were pooled using random-effect meta-analyses.

MAIN OUTCOMES AND MEASURES: Primary outcome was BPD using trial-specific definitions, which was further stratified for RCTs that used a more stringent BPD definition based on systematic pulse oximetry assessment at 36 weeks' postmenstrual age. Other outcomes were BPD, death, BPD severity, or combined BPD and death.

RESULTS: Among the 2760 studies screened, 4 RCTs were included, which involved 2304 infants (1223 boys [53.1%]; mean [SD] gestational age, 26.5 [1.6] weeks). Enteral supplementation with high-dose DHA was associated with neither BPD (4 studies [n = 2186 infants]; RR, 1.07 [95% CI, 0.86-1.34]; P = .53; I2 = 72%) nor BPD or death (4 studies [n = 2299 infants]; RR, 1.04 [95% CI, 0.91-1.18]; P = .59; I2 = 61%). However, an inverse association with BPD was found in RCTs that used a more stringent BPD definition (2 studies [n = 1686 infants]; RR, 1.20 [95% CI, 1.01-1.42]; P = .04; I2 = 48%). Additionally, DHA was inversely associated with moderate-to-severe BPD (3 studies [n = 1892 infants]; RR, 1.16 [95% CI, 1.04-1.29]; P = .008; I2 = 0%).

Methods: We expanded a prior framework based on Grading of Evidence, Assessment, Development and Evaluation (GRADE) to include GER. The revised framework is applied systematically during the formulation of research questions and comprises: (1) assessment of the GRADE strength and quality rating of recommendations; (2) mandatory inclusion of research questions identified from a global stakeholder survey; and (3) selection of the GER standards and principles most relevant to the question through discussion and consensus. For each question, we articulated: (1) the most appropriate and robust study design; (2) an alternative pragmatic design if the ideal design was not feasible; and (3) the methodological challenges facing researchers through identifying potential biases.

Results: We identified 39 research questions, 7 overarching research approaches and 13 discrete feasible study designs. Availability and accessibility were most frequently identified as the GER standards and principles to consider when planning studies, followed by privacy and confidentiality. Selection and detection bias were the primary methodological challenges across mixed methods, quantitative and qualitative studies. A lack of generalisability potentially limits the use of study results with non-participation in research potentially highest in more vulnerable populations.

METHODOLOGY/PRINCIPAL FINDINGS: We used 13 nuclear microsatellite loci (on 911 individuals) and mitochondrial COI sequences to gain a better understanding of the historical and contemporary movements of Ae. albopictus in the Indo-Pacific region and to characterize its population structure. Approximate Bayesian computation (ABC) was employed to test competing historical routes of invasion of Ae. albopictus within the Southeast (SE) Asian/Australasian region. Our ABC results show that Ae. albopictus was most likely introduced to New Guinea via mainland Southeast Asia, before colonizing the Solomon Islands via either Papua New Guinea or SE Asia. The analysis also supported that the recent incursion into northern Australia's Torres Strait Islands was seeded chiefly from Indonesia. For the first time documented in this invasive species, we provide evidence of a recently colonized population (the Torres Strait Islands) that has undergone rapid temporal changes in its genetic makeup, which could be the result of genetic drift or represent a secondary invasion from an unknown source.