Long-term cardiometabolic health in people born after assisted reproductive technology: a multi-cohort analysis.

AIMS: To examine associations of assisted reproductive technology (ART) conception (vs. natural conception: NC) with offspring cardiometabolic health outcomes and whether these differ with age. METHODS AND RESULTS: Differences in systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), lipids, and hyperglycaemic/insulin resistance markers were examined using multiple linear regression models in 14 population-based birth cohorts in Europe, Australia, and Singapore, and results were combined using meta-analysis. Change in cardiometabolic outcomes from 2 to 26 years was examined using trajectory modelling of four cohorts with repeated measures. 35 938 (654 ART) offspring were included in the meta-analysis. Mean age ranged from 13 months to 27.4 years but was <10 years in 11/14 cohorts. Meta-analysis found no statistical difference (ART minus NC) in SBP (-0.53 mmHg; 95% CI:-1.59 to 0.53), DBP (-0.24 mmHg; -0.83 to 0.35), or HR (0.02 beat/min; -0.91 to 0.94). Total cholesterol (2.59%; 0.10-5.07), HDL cholesterol (4.16%; 2.52-5.81), LDL cholesterol (4.95%; 0.47-9.43) were statistically significantly higher in ART-conceived vs. NC offspring. No statistical difference was seen for triglycerides (TG), glucose, insulin, and glycated haemoglobin. Long-term follow-up of 17 244 (244 ART) births identified statistically significant associations between ART and lower predicted SBP/DBP in childhood, and subtle trajectories to higher SBP and TG in young adulthood; however, most differences were not statistically significant. CONCLUSION: These findings of small and statistically non-significant differences in offspring cardiometabolic outcomes should reassure people receiving ART. Longer-term follow-up is warranted to investigate changes over adulthood in the risks of hypertension, dyslipidaemia, and preclinical and clinical cardiovascular disease.

Using Digital Tools to Study the Health of Adults Born Preterm at a Large Scale: e-Cohort Pilot Study.

BACKGROUND: Preterm birth is a global health concern. Its adverse consequences may persist throughout the life course, exerting a potentially heavy burden on families, health systems, and societies. In high-income countries, the first children who benefited from improved care are now adults entering middle age. However, there is a clear gap in the knowledge regarding the long-term outcomes of individuals born preterm. OBJECTIVE: This study aimed to assess the feasibility of recruiting and following up an e-cohort of adults born preterm worldwide and provide estimations of participation, characteristics of participants, the acceptability of questions, and the quality of data collected. METHODS: We implemented a prospective, open, observational, and international e-cohort pilot study (Health of Adult People Born Preterm-an e-Cohort Pilot Study [HAPP-e]). Inclusion criteria were being an adult (aged ≥18 years), born preterm (<37 weeks of gestation), having internet access and an email address, and understanding at least 1 of the available languages. A large, multifaceted, and multilingual communication strategy was established. Between December 2019 and June 2021, inclusion and repeated data collection were performed using a secured web platform. We provided descriptive statistics regarding participation in the e-cohort, namely, the number of persons who registered on the platform, signed the consent form, initiated and completed the baseline questionnaire, and initiated and completed the follow-up questionnaire. We also described the main characteristics of the HAPP-e participants and provided an assessment of the quality of the data and the acceptability of sensitive questions. RESULTS: As of December 31, 2020, a total of 1004 persons had registered on the platform, leading to 527 accounts with a confirmed email and 333 signed consent forms. A total of 333 participants initiated the baseline questionnaire. All participants were invited to follow-up, and 35.7% (119/333) consented to participate, of whom 97.5% (116/119) initiated the follow-up questionnaire. Completion rates were very high both at baseline (296/333, 88.9%) and at follow-up (112/116, 96.6%). This sample of adults born preterm in 34 countries covered a wide range of sociodemographic and health characteristics. The gestational age at birth ranged from 23+6 to 36+6 weeks (median 32, IQR 29-35 weeks). Only 2.1% (7/333) of the participants had previously participated in a cohort of individuals born preterm. Women (252/333, 75.7%) and highly educated participants (235/327, 71.9%) were also overrepresented. Good quality data were collected thanks to validation controls implemented on the web platform. The acceptability of potentially sensitive questions was excellent, as very few participants chose the "I prefer not to say" option when available. CONCLUSIONS: Although we identified room for improvement in specific procedures, this pilot study confirmed the great potential for recruiting a large and diverse sample of adults born preterm worldwide, thereby advancing research on adults born preterm.

Rapid determination of L-ascorbic acid content in vitamin C serums by ultra-high-performance liquid chromatography-tandem mass spectrometry.

OBJECTIVE: This study aimed to develop and validate a rapid, simple, accurate and precise analytical method for the quantification of L-AA in vitamin C serums. Moreover, the developed method was further applied to determine L-AA in eight different brands of vitamin C serums. A complementary study was also carried out to evaluate the stability of L-AA in the vitamin C serum samples after 15, 30, 45 and 60 days of storage at ambient temperature (15-35°C). METHODS: Ultra-high-performance liquid chromatography-tandem mass spectrometry was applied. RESULTS: Quantitative analyses were performed with a total chromatographic run time of 1.5 min by matrix-matched calibration, and the analytical curve was linear over the range of 1-1700 µg L-1 with a correlation coefficient of 0.9998. The limits of detection (LOD) and quantification (LOQ) were 0.3 and 1.0 µg L-1 , respectively. Intra- and inter-assay precisions, expressed in terms of relative standard deviation, ranged from 0.3% and 2.2%, respectively, and recoveries in concentration levels of 1 and 5 µg L-1 were 103.9% and 101.2%, respectively. The proposed analytical method was successfully applied to determine the L-AA content in eight commercial vitamin C serum samples. The stability of the target analyte in samples stored at ambient temperature (15-35°C) was evaluated throughout 60 days with a 15-day interval between analyses. At 0 days, L-AA content in samples ranged from 1.05 to 169.91 mg L-1 , which decreases over time. CONCLUSION: The proposed method could be powerful in routine analyses to ensure the quantification of L-AA in vitamin C serums since it proved to be a simple, reliable, fast, precise, accurate and sensitive analytical method.

OBJECTIF: Cette étude visait à développer et valider une méthode analytique rapide, simple, exacte et précise pour la quantification de l'acide L-ascorbique dans les sérums à la vitamine C. De plus, la méthode développée a été appliquée pour déterminer l'acide L-ascorbique dans huit différentes marques de sérums à la vitamine C. Une étude complémentaire a également été réalisée pour évaluer la stabilité de l'acide L-ascorbique dans les échantillons de sérum à la vitamine C après 15, 30, 45 et 60 jours de conservation à température ambiante (15 à 35 °C). MÉTHODES: La chromatographie en phase liquide à haute performance avec spectrométrie de masse en tandem a été employée. RÉSULTATS: Des analyses quantitatives ont été réalisées avec une durée totale d'exécution chromatographique de 1,5 minute par calibration matricielle appariée, et la courbe analytique était linéaire sur la plage de 1 à 1700 µg L-1 avec un coefficient de corrélation de 0,9998. La limite de détection (LD) et la limite de quantification (LQ) ont été déterminées à 0,3 et 1,0 µg L−1 , respectivement. Les précisions intra- et inter-essais, exprimées en termes d'écart-type relatif, étaient de 0,3 % et 2,2 %, respectivement, et les récupérations aux niveaux de concentration de 1 et 5 µg L-1 étaient de 103,9 % et 101,2 %, respectivement. La méthode analytique proposée a été employée avec succès pour déterminer la teneur en acide L-ascorbique de huit échantillons de sérum à la vitamine C commerciaux. La stabilité de l'analyte cible dans les échantillons conservés à température ambiante (15 à 35 °C) a été évaluée sur 60 jours avec un intervalle de 15 jours entre les analyses. À 0 jour, la teneur en acide L-ascorbique dans les échantillons était comprise entre 1,05 et 169,91 µg L-1 , ce qui diminue au fil du temps. CONCLUSION: La méthode proposée pourrait être puissante dans les analyses de routine pour assurer la quantification de l'acide L-ascorbique dans les sérums à la vitamine C puisqu'elle s'est avérée être une méthode analytique simple, fiable, rapide, précise, exacte et sensible.

Never-breastfed children face a higher risk of suboptimal cognition at 2 years of corrected age: A multinational cohort of very preterm children.

In a cohort of children born very preterm (VPT), we investigated the association between breast milk feeding (BMF) initiation and its duration on cognitive development at 2 years of corrected age. Data were obtained from the Effective Perinatal Intensive Care in Europe population-based prospective cohort of children born <32 weeks of gestation, in 11 European countries, in 2011-2012. The study sample included 4323 children. Nonverbal cognitive ability was measured applying the Parental Report of Children's Abilities, except for France where the problem-solving domain of the Ages & Stages Questionnaire was used. Verbal cognition was based on the number of words the child could say. To determine the association between BMF (mother's own milk) and nonverbal and verbal cognition (outcome categorized as optimal and suboptimal), adjusted risk ratios (aRRs) were estimated fitting Poisson regression models, with inverse probability weights to account for nonresponse bias. Overall, 16% and 11% of the children presented suboptimal nonverbal and verbal cognition, respectively. Never BMF was associated with a significantly increased risk for suboptimal nonverbal (aRR = 1.29, 95% confidence interval [CI] = 1.09-1.53) and verbal (aRR = 1.45, 95% CI = 1.09-1.92) cognitive development compared with those ever breastfed, after adjustment for perinatal and sociodemographic characteristics. Compared with children breastfed 6 months or more, children with shorter BMF duration exhibited a statistically nonsignificant elevated aRR. VPT children fed with breast milk had both improved nonverbal and verbal cognitive development at 2 years in comparison with never breastfed, independently of perinatal and sociodemographic characteristics. This study encourages targeted interventions to promote BMF among these vulnerable children.

What drives change in neonatal intensive care units? A qualitative study with physicians and nurses in six European countries.

BACKGROUND: Innovation is important to improve patient care, but few studies have explored the factors that initiate change in healthcare organizations. METHODS: As part of the European project EPICE on evidence-based perinatal care, we carried out semi-structured interviews (N = 44) with medical and nursing staff from 11 randomly selected neonatal intensive care units in 6 countries. The interviews focused on the most recent clinical or organizational change in the unit relevant to the care of very preterm infants. Thematic analysis was performed using verbatim transcripts of recorded interviews. RESULTS: Reported changes concerned ventilation, feeding and nutrition, neonatal sepsis, infant care, pain management and care of parents. Six categories of drivers to change were identified: availability of new knowledge or technology; guidelines or regulations from outside the unit; need to standardize practices; participation in research; occurrence of adverse events; and wish to improve care. Innovations originating within the unit, linked to the availability of new technology and seen to provide clear benefit for patients were more likely to achieve consensus and rapid implementation. CONCLUSIONS: Innovation can be initiated by several drivers that can impact on the success and sustainability of change.

Low breastfeeding continuation to 6 months for very preterm infants: A European multiregional cohort study.

Breastfeeding confers multiple benefits for the health and development of very preterm infants, but there is scarce information on the duration of breastfeeding after discharge from the neonatal intensive care unit (NICU). We used data from the Effective Perinatal Intensive Care in Europe population-based cohort of births below 32 weeks of gestation in 11 European countries in 2011-2012 to investigate breastfeeding continuation until 6 months. Clinical and sociodemographic characteristics were collected from obstetric and neonatal medical records as well as parental questionnaires at 2 years of corrected age. Among 3,217 ever-breastfed infants, 34% were breastfeeding at 6 months of age (range across countries from 25% to 56%); younger and less educated mothers were more likely to stop before 6 months (adjusted relative risk [aRR] <25 years: 0.68, 95% CI [0.53, 0.88], vs. 25-34 years; lower secondary: 0.58, 95% CI [0.45, 0.76] vs. postgraduate education). Multiple birth, bronchopulmonary dysplasia (BPD), and several neonatal transfers reduced the probability of continuation but not low gestational age, fetal growth restriction, congenital anomalies, or severe neonatal morbidities. Among infants breastfeeding at discharge, mixed versus exclusive breast milk feeding at discharge was associated with stopping before 6 months: aRR = 0.60, 95% CI [0.48, 0.74]. Low breastfeeding continuation rates in this high-risk population call for more support to breastfeeding mothers during and after the neonatal hospitalization, especially for families with low socio-economic status, multiples, and infants with BPD. Promotion of exclusive breastfeeding in the NICU may constitute a lever for improving breastfeeding continuation after discharge.

Prevalence and duration of breast milk feeding in very preterm infants: A 3-year follow-up study and a systematic literature review.

BACKGROUND: The World Health Organization recommends exclusive breast milk feeding until 6 months and continuing up to 2 years of age; little is known about whether very preterm infants are fed in accordance with these recommendations. We aimed to describe the prevalence and duration of breast milk feeding in very preterm children and to systematically review internationally published data. METHODS: We evaluated breast milk feeding initiation and duration in very preterm children born in 2 Portuguese regions (2011-2012) enrolled in the EPICE cohort and followed-up to the age of 3 (n = 466). We searched PubMed® from inception to January 2017 to identify original studies reporting the prevalence and/or duration of breast milk feeding in very preterm children. RESULTS: 91.0% of children received some breast milk feeding and 65.3% were exclusively breast fed with a median duration of 2 months for exclusive and 3 months for any breast milk; only 9.9% received exclusive breast milk for at least 6 months, 10.2% received any breast milk for 12 months or more, and 2.0% for up to 24 months. The literature review identified few studies on feeding after hospital discharge (n = 9); these also reported a low prevalence of exclusive breast milk feeding at 6 months (1.0% to 27.0%) and of any breast milk at 12 months (8.0% to 12.0%). CONCLUSIONS: The duration of breast milk feeding among Portuguese very preterm infants was shorter than recommended. However, this appears to be common globally. Research is needed to inform strategies to promote continued breast milk feeding.

Room for improvement in breast milk feeding after very preterm birth in Europe: Results from the EPICE cohort.

Breast milk feeding (BMF) is associated with lower neonatal morbidity in the very preterm infant (<32 weeks gestation) and breastfeeding is beneficial for maternal health. Previous studies show large variations in BMF after very preterm birth and recognize the need for targeted breastfeeding support in the neonatal intensive care units (NICU). In a European collaboration project about evidence-based practices after very preterm birth, we examined the association between maternal, obstetric, and infant clinical factors; neonatal and maternal care unit policies; and BMF at discharge from the NICU. In multivariable analyses, covariates associated with feeding at discharge were first investigated as predictors of any BMF and in further analysis as predictors of exclusive or partial BMF. Overall, 58% (3,826/6,592) of the infants received any BMF at discharge, but there were large variations between regions (range 36-80%). Primiparity, administration of antenatal corticosteroids, first enteral feed <24 hr after birth, and mother's own milk at first enteral feed were predictors positively associated with any BMF at discharge. Vaginal delivery, singleton birth, and receiving mother's own milk at first enteral feed were associated with exclusive BMF at discharge. Units with a Baby Friendly Hospital accreditation improved any BMF at discharge; units with protocols for BMF and units using donor milk had higher rates of exclusive BMF at discharge. This study suggests that there is a high potential for improving BMF through policies and support in the NICU.

Evaluation of the anti-inflammatory action of curcumin analog (DM1): Effect on iNOS and COX-2 gene expression and autophagy pathways.

This work describes the anti-inflammatory effect of the curcumin-analog compound, sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate (DM1), and shows that DM1 modulates iNOS and COX-2 gene expression in cultured RAW 264.7 cells and induces autophagy on human melanoma cell line A375.

Performance of In Silico Tools for the Evaluation of UGT1A1 Missense Variants.

Variations in the gene encoding uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) are particularly important because they have been associated with hyperbilirubinemia in Gilbert's and Crigler-Najjar syndromes as well as with changes in drug metabolism. Several variants associated with these phenotypes are nonsynonymous single-nucleotide polymorphisms (nsSNPs). Bioinformatics approaches have gained increasing importance in predicting the functional significance of these variants. This study was focused on the predictive ability of bioinformatics approaches to determine the pathogenicity of human UGT1A1 nsSNPs, which were previously characterized at the protein level by in vivo and in vitro studies. Using 16 Web algorithms, we evaluated 48 nsSNPs described in the literature and databases. Eight of these algorithms reached or exceeded 90% sensitivity and six presented a Matthews correlation coefficient above 0.46. The best-performing method was MutPred, followed by Sorting Intolerant from Tolerant (SIFT). The prediction measures varied significantly when predictors such us SIFT, polyphen-2, and Prediction of Pathological Mutations on Proteins were run with their native alignment generated by the tool, or with an input alignment that was strictly built with UGT1A1 orthologs and manually curated. Our results showed that the prediction performance of some methods based on sequence conservation analysis can be negatively affected when nsSNPs are positioned at the hypervariable or constant regions of UGT1A1 ortholog sequences.

Genetic Identification and Technological Potential of Indigenous Lactic Acid Bacteria Isolated from Alheira, a Traditional Portuguese Sausage.

Alheira is a naturally fermented meat sausage traditionally made in the Portuguese region of Trás-os-Montes. Lactic acid bacteria (LAB) are the dominant microorganisms in alheira and can endow it with various technological properties. This study aimed (1) to characterize technological features and in vitro antimicrobial activity of LAB isolated from alheira, and (2) to reveal associations between such phenotypic characteristics and the isolates species identified through amplification and sequencing of the 16S ribosomal gene. Sixty-two LAB isolates were identified and Enterococcus (E.) faecium corresponded to 32.3% of isolates, followed by Leuconostoc (L.) mesenteroides (19.4%) and Latilactobacillus (Lb.) sakei (17.7%), aligning with previous research on traditional Portuguese fermented meat sausages. The phenotypic analysis of LAB isolates indicated diverse acidification capacities, proteolytic activities, and inhibitory effects against foodborne pathogens Listeria (L.) monocytogenes, Salmonella (S.) Typhimurium and Staphylococcus (S.) aureus. Overall, lactobacilli displayed high inhibition activity against the pathogens S. aureus, L. monocytogenes, and S. Typhimurium. Although the mechanisms for the inhibition of pathogen growth need to be further elucidated, these findings enhance our understanding of LAB diversity and functionality in alheira sausages, contributing to product safety and quality.

Seroprevalence of Protective Antibodies Against Influenza and the Reduction of the Influenza Incidence Rate: An Annual Repeated Cross-Sectional Study From 2014 to 2019.

BACKGROUND: Seroepidemiological studies provide estimates of population-level immunity, prevalence/incidence of infections, and evaluation of vaccination programs. We assessed the seroprevalence of protective antibodies against influenza and evaluated the correlation of seroprevalence with the cumulative annual influenza incidence rate. METHODS: We conducted an annual repeated cross-sectional seroepidemiological survey, during June-August, from 2014 to 2019, in Portugal. A total of 4326 sera from all age groups, sex, and regions was tested by hemagglutination inhibition assay. Seroprevalence and geometric mean titers (GMT) of protective antibodies against influenza were assessed by age group, sex, and vaccine status (65+ years old). The association between summer annual seroprevalence and the difference of influenza incidence rates between one season and the previous one was measured by Pearson correlation coefficient (r). RESULTS: Significant differences in seroprevalence of protective antibodies against influenza were observed in the population. Higher seroprevalence and GMT for A(H1N1)pdm09 and A(H3N2) were observed in children (5-14); influenza B seroprevalence in adults 65+ was 1.6-4.4 times than in children (0-4). Vaccinated participants (65+) showed significant higher seroprevalence/GMT for influenza. A strong negative and significant correlation was found between seroprevalence and ILI incidence rate for A(H1N1)pdm09 in children between 5 and 14 (r = -0.84; 95% CI, -0.98 to -0.07); a weak negative correlation was observed for A(H3N2) and B/Yamagata (r ≤ -0.1). CONCLUSIONS: The study provides new insight into the anti-influenza antibodies seroprevalence measured in summer on the ILI incidence rate in the next season and the need for adjusted preventive health care measures to prevent influenza infection and transmission.

Lactic acid bacteria from artisanal raw goat milk cheeses: technological properties and antimicrobial potential.

In cheese-making, a starter culture composed of adequately chosen lactic acid bacteria (LAB) may be suitable to ensure the rapid acidification of milk, improve textural and sensory characteristics, and avoid pathogen proliferation. In this work, 232 LAB isolates collected from artisanal goat's raw milk cheeses produced in Portugal were evaluated for their antimicrobial capacity (at 10 and 37°C), as well as their acidifying and proteolytic properties. Among the 232 isolates, at least 98% of those isolated in De Man- Rogosa-Sharpe (MRS) agar presented antagonism against Listeria monocytogenes, Salmonella Typhimurium, or Staphylococcus aureus, whereas less than 28.1% of M17-isolated LAB showed antagonism against these pathogens. M17-isolated LAB displayed better results than MRS ones in terms of acidifying capacity. As for the proteolytic assay, only 2 MRS isolates showed casein hydrolysis capacity. Principal component analyses and molecular characterization of a subset of selected isolates were conducted to identify those with promising capacities and to correlate the identified LAB genera and species with their antimicrobial, acidifying, and/or proteolytic properties. Lactococcus strains were associated with the highest acidifying capacity, whereas Leuconostoc and Lacticaseibacillus strains were more related to antimicrobial capacities. Leuconostoc mesenteroides, Lactococcus lactis, and Lacticaseibacillus paracasei were the predominant organisms found. The results of this work highlight various strains with pathogen inhibition capacity and suitable technological properties to be included in a customized starter culture. In future work, it is necessary to appropriately define the starter culture and implement it in the cheese-making process to evaluate if the in-vitro capacities are observable in a real food system.

Impact of UGT1A1 gene variants on total bilirubin levels in Gilbert syndrome patients and in healthy subjects.

The Gilbert syndrome is a benign form of unconjugated hyperbilirubinemia, mainly associated with alterations in UGT1A1 gene. This work investigated the effect of UGT1A1 variants on total bilirubin levels in Gilbert patients (n=45) and healthy controls (n=161). Total bilirubin levels were determined using a colorimetric method; molecular analysis of exons 1-5 and two UGT1A1 promoter regions were performed by direct sequencing and automatic analysis of fragments. Five in silico methods predicted the effect of new identified variants. A significant different allelic distribution, in Gilbert patients and in controls, was found for two promoter polymorphisms. Among patients, 82.2% were homozygous and 17.8% heterozygous for the c.-41_-40dupTA allele; in control group, 9.9% were homozygous and 43.5% heterozygous for this promoter variant, while 46.6% (n=75) presented the [A(TA)6TAA]. For the T>G transition at c.-3279 promoter region, in patients, 86.7% were homozygous and 13.3% heterozygous; in control group, 33.5% were homozygous for the wild type allele, 44.1% were heterozygous and 22.4% homozygous for the mutated allele. The two polymorphisms were in Hardy-Weinberg equilibrium in both groups. Sequencing of UGT1A1 coding region identified nine novel variants, five in patients and four in controls. In silico analysis of these amino acids replacements predicted four of them as benign and three as damaging. In conclusion, we demonstrated that total bilirubin levels are mainly determined by the TA duplication in the TATA-box promoter and by the c.-3279T>G variant. Alterations in the UGT1A1 coding region seem to be associated with increased bilirubin levels, and, therefore, with Gilbert syndrome.

Angle Class III malocclusion treated with mandibular first molar extractions.

A Class III malocclusion associated with dental asymmetry is a complex diagnostic and treatment problem in orthodontics. The goals of maintaining or improving the facial profile and achieving good function are decisive factors when considering whether to plan a surgical or a nonsurgical treatment approach. A fixed appliance in combination with extractions could be considered for nonsurgical management of this type of malocclusion in the permanent dentition. This article presents the results of an orthodontic approach to a Class III subdivision malocclusion in an adult treated with mandibular first molar extractions. The extractions provided the space needed to correct the overjet and overbite and to improve the intercuspation.

Machine learning methods to predict attrition in a population-based cohort of very preterm infants.

The timely identification of cohort participants at higher risk for attrition is important to earlier interventions and efficient use of research resources. Machine learning may have advantages over the conventional approaches to improve discrimination by analysing complex interactions among predictors. We developed predictive models of attrition applying a conventional regression model and different machine learning methods. A total of 542 very preterm (< 32 gestational weeks) infants born in Portugal as part of the European Effective Perinatal Intensive Care in Europe (EPICE) cohort were included. We tested a model with a fixed number of predictors (Baseline) and a second with a dynamic number of variables added from each follow-up (Incremental). Eight classification methods were applied: AdaBoost, Artificial Neural Networks, Functional Trees, J48, J48Consolidated, K-Nearest Neighbours, Random Forest and Logistic Regression. Performance was compared using AUC- PR (Area Under the Curve-Precision Recall), Accuracy, Sensitivity and F-measure. Attrition at the four follow-ups were, respectively: 16%, 25%, 13% and 17%. Both models demonstrated good predictive performance, AUC-PR ranging between 69 and 94.1 in Baseline and from 72.5 to 97.1 in Incremental model. Of the whole set of methods, Random Forest presented the best performance at all follow-ups [AUC-PR1: 94.1 (2.0); AUC-PR2: 91.2 (1.2); AUC-PR3: 97.1 (1.0); AUC-PR4: 96.5 (1.7)]. Logistic Regression performed well below Random Forest. The top-ranked predictors were common for both models in all follow-ups: birthweight, gestational age, maternal age, and length of hospital stay. Random Forest presented the highest capacity for prediction and provided interpretable predictors. Researchers involved in cohorts can benefit from our robust models to prepare for and prevent loss to follow-up by directing efforts toward individuals at higher risk.

Behavioral and emotional outcomes at preschool age in children born very preterm: The role of breast milk feeding practices.

BACKGROUND: Breast milk feeding (BMF) improved neurodevelopment in children born very preterm (VPT, <32 weeks of gestation), but knowledge about its effect on other mental health outcomes remains limited. OBJECTIVE: To estimate the association of BMF practices with behavioral and emotional problems at preschool age in children born VPT. METHODS: We studied 263 children born VPT during 2011-12 and enrolled in the Portuguese EPICE cohort. At the age of 3, information on BMF initiation and duration was collected and behavioral and emotional problems were assessed using the parents' completed Child Behavior Checklist 1.5-5 years (CBCL/1½-5). Children were categorized for all CBCL/1½-5 sub-scales and for Diagnostic and Statistical Manual of Mental Disorders (DSM5)-oriented scales. Risk ratios were estimated to assess the association of BMF with subclinical/clinical problems, fitting a Poisson regression. RESULTS: Behavioral or emotional subclinical/clinical problems were found in almost 20% of children (11.8% in the clinical range). BMF was consistently associated with lower adverse behavioral and emotional outcomes, particularly risks of externalizing problems, somatic complaints, aggressive behavior, as well as autism spectrum and attention deficit/hyperactivity symptoms, although the magnitude of the unadjusted risks was attenuated by adjustment for relevant confounders and wider confidence intervals included the null. CONCLUSION: Lower exposure to BMF seemed to increase the risk of adverse behavioral and emotional outcomes at preschool age in children born VPT. These results raise questions about explanatory pathways and strengthen evidence underpinning BMF promotion for VPT children.

Regional differences in the quality of maternal and neonatal care during the COVID-19 pandemic in Portugal: Results from the IMAgiNE EURO study.

OBJECTIVE: To compare women's perspectives on the quality of maternal and newborn care (QMNC) around the time of childbirth across Nomenclature of Territorial Units for Statistics 2 (NUTS-II) regions in Portugal during the COVID-19 pandemic. METHODS: Women participating in the cross-sectional IMAgiNE EURO study who gave birth in Portugal from March 1, 2020, to October 28, 2021, completed a structured questionnaire with 40 key WHO standards-based quality measures. Four domains of QMNC were assessed: (1) provision of care; (2) experience of care; (3) availability of human and physical resources; and (4) reorganizational changes due to the COVID-19 pandemic. Frequencies for each quality measure within each QMNC domain were computed overall and by region. RESULTS: Out of 1845 participants, one-third (33.7%) had a cesarean. Examples of high-quality care included: low frequencies of lack of early breastfeeding and rooming-in (8.0% and 7.7%, respectively) and informal payment (0.7%); adequate staff professionalism (94.6%); adequate room comfort and equipment (95.2%). However, substandard practices with large heterogeneity across regions were also reported. Among women who experienced labor, the percentage of instrumental vaginal births ranged from 22.3% in the Algarve to 33.5% in Center; among these, fundal pressure ranged from 34.8% in Lisbon to 66.7% in Center. Episiotomy was performed in 39.3% of noninstrumental vaginal births with variations between 31.8% in the North to 59.8% in Center. One in four women reported inadequate breastfeeding support (26.1%, ranging from 19.4% in Algarve to 31.5% in Lisbon). One in five reported no exclusive breastfeeding at discharge (22.1%; 19.5% in Lisbon to 28.2% in Algarve). CONCLUSION: Urgent actions are needed to harmonize QMNC and reduce inequities across regions in Portugal.