Examining the relationship between the environmental impact of diet and child growth from a co-benefit perspective.

The adoption of diets that minimize both their environmental impacts and weight excess in children would be a major co-benefit for climate change mitigation. We evaluated the relationship between child diet-related environmental impact and anthropometric characteristics in an Italian birth cohort. The study involved 2127 children of the Piccolipiù birth cohort. At 4 years, their diet in the previous two months was assessed through a questionnaire, from which we derived individual: (i) diet-related daily greenhouse gas emissions (GHGE), (ii) land use (LU), (iii) adherence to the Mediterranean Diet (MD) and (iv) red meat consumption. We related these variables with overweight and obesity, waist circumference, and height at 4 years using regression models adjusted for a priori selected confounders. Diet-related GHGE and LU had a positive weak association with overweight and obesity, with an odds ratio (OR) for the fourth vs. second quartile of 1.30 for both GHGE (95% confidence intervals -CI-: 0.96; 1.77) and LU (95% CI: 0.96-1.76). Both OR estimates increased after adjustment for energy intake. GHGE and LU were not associated with height, with the exception of shorter children in the first quartile. A high vs. low MD adherence was associated with an increase in height Z-score of 0.11 (95% CI 0.01; 0.21). No association was found for red meat consumption. These results suggest that lowering the impact of high environmental impact diets may have, if anything, beneficial effects on child obesity, overweight, and height, with pro-MD patterns playing an important role.

Maternal antenatal mental health and its associations with perinatal outcomes and the use of healthcare services in children from the NINFEA birth cohort study.

To investigate the associations between maternal mental health disorders before and during pregnancy and perinatal outcomes and child healthcare utilization between 6 and 18 months of age. Among the 6814 mother-child pairs from the Italian Internet-based NINFEA birth cohort, maternal depression, anxiety, and sleep disorders diagnosed by a physician before and during pregnancy were assessed through self-reported questionnaires completed during pregnancy and 6 months after delivery. Perinatal outcomes (preterm birth, birth weight, small for gestational age, congenital anomalies, and neonatal intensive care unit (NICU)) and children's healthcare utilization (emergency department (ED) visits, hospitalizations, and outpatient visits) were reported by mothers at 6 and 18 months postpartum. We used regression models adjusted for maternal age, education, parity, country of birth, region of delivery, and household income. Maternal mental health disorders were not associated with perinatal outcomes, except for depression, which increased the risk of offspring admission to NICU, and anxiety disorders during pregnancy, which were associated with preterm birth and lower birth weight. Children born to mothers with depression/anxiety disorders before pregnancy, compared to children of mothers without these disorders, had an increased odds of a visit to ED for any reason (odds ratio (ORadj) = 1.26, 95% confidence interval (CI): 1.02-1.54), of an ED visit resulting in hospitalization (ORadj = 1.75, 95%CI: 1.27-2.42), and of planned hospital admissions (ORadj = 1.55, 95%CI: 1.01-2.40). These associations with healthcare utilization were similar for mental disorders also during pregnancy. The association pattern of maternal sleep disorders with perinatal outcomes and child healthcare utilization resembled that of maternal depression and/or anxiety disorders with these outcomes.   Conclusion: Antenatal maternal mental health is a potential risk factor for child-health outcomes and healthcare use. Early maternal mental health interventions may help to promote child health and reduce healthcare costs. What is Known: • Poor maternal mental health affects pregnancy outcomes and child health, and children of mothers with mental health conditions tend to have increased healtcare utilization. • Parents with poor mental health often face challenges in caring for their children and have less parenting self-efficacy, which could potentially lead to frequent medical consultations for minor health issues. What is New: • Maternal pre-pregnancy mental disorders were not associated with preterm birth, low birth weight, SGA, and congenital anomalies, except for depression, which increased the risk of offspring admission to NICU. Anxiety disorders during pregnancy were associated with lower birth weight and an increased odds of preterm birth. • Maternal depression and/or anxiety and sleep disorders, both before and during pregnancy, were associated with an increase in children's healthcare utilization between 6 and 18 months of life.

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.

Identifying and appraising outcome measures for severe asthma: a systematic review.

BACKGROUND: Valid outcome measures are imperative to evaluate treatment response, yet the suitability of existing end-points for severe asthma is unclear. This review aimed to identify outcome measures for severe asthma and appraise the quality of their measurement properties. METHODS: A literature search was performed to identify "candidate" outcome measures published between 2018 and 2020. A modified Delphi exercise was conducted to select "key" outcome measures within healthcare professional, patient, pharmaceutical and regulatory stakeholder groups. Initial validation studies for "key" measures were rated against modified quality criteria from COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). The evidence was discussed at multi-stakeholder meetings to ratify "priority" outcome measures. Subsequently, four bibliographic databases were searched from inception to 20 July 2020 to identify development and validation studies for these end-points. Two reviewers screened records, extracted data, assessed their methodological quality and graded the evidence according to COSMIN. RESULTS: 96 outcome measures were identified as "candidates", 55 as "key" and 24 as "priority" for severe asthma, including clinical, healthcare utilisation, quality of life, asthma control and composite. 32 studies reported measurement properties of 17 "priority" end-points from the latter three domains. Only the Severe Asthma Questionnaire and Childhood Asthma Control Test were developed with input from severe asthma patients. The certainty of evidence was "low" to "very low" for most "priority" end-points across all measurement properties and none fulfilled all quality standards. CONCLUSIONS: Only two outcome measures had robust developmental data for severe asthma. This review informed development of core outcome measures sets for severe asthma.

Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA).

BACKGROUND: Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) Working Group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies. METHODS: COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult and paediatric clinicians, pharmaceutical representatives, and health regulators from across Europe. Evidence included a systematic review of development, validity and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients' and carers' views about outcome measures. It was discussed using a modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria. RESULTS: Both adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z-scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire and Asthma Control Test or Childhood Asthma Control Test, while the adult COM set includes the Severe Asthma Questionnaire and Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately). CONCLUSIONS: This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.

Breastfeeding and presence of the companion of woman's choice during COVID-19 pandemic in Italy: regional population-based routine data and best practices at birth

OBJECTIVES: to describe the monthly trend of breastfeeding during hospitalization and the presence of companion of woman's choice during labour and birth, and the key regional responders' perspective of homogeneity/heterogeneity of the presence of the support person, before, during (February-May 2020), and after the first COVID-19 pandemic wave in a few Italian Regions. DESIGN: two-phase study. SETTING AND PARTICIPANTS: data from the italian birth certificate of six Italian Regions between 01.01.2019 and 31.03.2021 were analysed. Semi-structured interviews were conducted with the key regional respondents. MAIN OUTCOME MEASURES: the frequency distributions of breastfeeding and the presence of companion of woman's choice were calculated as a whole and for each Region. RESULTS: the infant feeding practices experienced smaller changes during COVID-19 pandemic than the presence of the companion of woman's choice during labour and birth, from January 2019 to March 2021. The highest value of exclusive breastfeeding was recorded in September 2020 (72.1%; 95%CI 71.3-72.8) in all Regions, while the lowest was recorded in March 2021 (62.5%; 95%CI 61.5-63.4). The presence of companion of woman's choice during labour and birth decreased during the pandemic and did not return to pre-pandemic levels. The highest value of presence of father during birth was recorded in March 2019 (59.0%; 95%CI 58.2-59.8), while the lowest in April 2020 (50.0%; 95%CI 49.1-50.8). The main emerging themes were: the existence of national, regional and local indications; the facilitators (e.g., Baby-Friendly Hospital Initiative implementation, strong motivation of the staff) and the critical points (e.g., inadequate analysis of the clinical-epidemiological context, inhomogeneous indications) of management of the support person presence. CONCLUSIONS: the emergency has changed the provision of health services that not always guaranteed the application of best practices. It would be desirable to work for assessing the appropriateness of the birth certificate data to collect more accurate information and to provide clinical recommendations.

Early factors associated with risk of developmental coordination disorder in very preterm children: A prospective area-based cohort study in Italy.

BACKGROUND: Developmental coordination disorder (DCD) is a motor disorder of unknown aetiology that may have long-term consequences on daily activities, and psychological and physical health. Studies investigating risk factors for DCD have so far provided inconsistent results. OBJECTIVES: To assess, using a parent-report screening tool, risk of DCD in school-age very preterm children born in Italy, and investigate the associated early biomedical and sociodemographic factors. METHODS: A prospective area-based cohort (804 children, response rate 73.4%) was assessed at 8-11 years of age in three Italian regions. Perinatal data were abstracted from medical records. DCD risk was measured using the Italian-validated version of the Developmental Coordination Disorder Questionnaire (DCDQ-IT). For this study, children with cognitive deficit (i.e. intelligence quotient <70), cerebral palsy, severe vision and hearing disabilities, and other impairments affecting movement were excluded. A total of 629 children were analysed. We used inverse probability weighting to account for loss to follow-up, and multilevel, multivariable modified Poisson models to obtain adjusted risk ratio (aRR) and 95% confidence interval (CI). Missing values in the covariates were imputed. RESULTS: 195 children (weighted proportion 31.8%, 95% CI 28.2, 35.6) scored positive on the DCDQ-IT, corresponding to the 15th centile of the reference Movement-ABC test. Factors associated with overall DCD risk were male sex (aRR 1.35, 95% CI 1.05, 1.73), intrauterine growth restriction (aRR 1.45, 95% CI 1.14, 1.85), retinopathy of prematurity (aRR 1.62, 95% CI 1.07, 2.45), and older maternal age at delivery (aRR 1.39, 95% CI 1.09, 1.77). Complete maternal milk feeding at discharge from the neonatal unit and higher parental socio-economic status were associated with decreased risk. CONCLUSIONS: Both biomedical and sociodemographic factors increase DCD risk. These findings can contribute to elucidating the origins of this disorder, and assist in the identification of children at risk for early referral and intervention.

Pregnancy outcomes in Italy during COVID-19 pandemic: a population-based cohort study.

OBJECTIVE: To compare the estimates of preterm birth (PTB; 22-36 weeks gestational age, GA) and stillbirth rates during COVID-19 pandemic in Italy with those recorded in the three previous years. DESIGN: A population-based cohort study of liveborn and stillborn infants was conducted using data from Regional Health Systems and comparing the pandemic period (March 1st , 2020-March 31st , 2021, N= 362,129) to an historical period (January 2017- February 2020, N=1,117,172). The cohort covered 84.3% of the births in Italy. METHODS: Poisson regressions were run in each Region and meta-analyses were performed centrally. We used an interrupted time series regression analysis to study the trend of preterm births from 2017 to 2021. MAIN OUTCOME MEASURES: The primary outcomes were PTB and stillbirths. Secondary outcomes were late PTB (32-36 weeks' GA), very PTB (<32 weeks' GA), and extremely PTB (<28 weeks' GA), overall and stratified into singleton and multiples. RESULTS: The pandemic period compared with the historical one was associated with a reduced risk for PTB (Risk Ratio: 0.91; 95% Confidence Interval, CI: 0.88, 0.93), late PTB (0.91; 0.88, 0.94), very PTB (0.88; 0.84, 0.91), and extremely PTB (0.88; 0.82, 0.95). In multiples, point estimates were not very different, but had wider CIs. No association was found for stillbirths (1.01; 0.90, 1.13). A linear decreasing trend in PTB rate was present in the historical period, with a further reduction after the lockdown. CONCLUSIONS: We demonstrated a decrease in PTB rate after the introduction of COVID-19 restriction measures, without an increase in stillbirths.

Prenatal exposure to PM10 and changes in DNA methylation and telomere length in cord blood.

BACKGROUND: Air pollution exposure in pregnancy can cause molecular level alterations that might influence later disease susceptibility. OBJECTIVES: We investigated DNA methylation (DNAm) and telomere length (TL) in the cord blood in relation to gestational PM10 exposure and explored potential gestational windows of susceptibility. METHODS: Cord blood epigenome-wide DNAm (N = 384) and TL (N = 500) were measured in children of the Italian birth cohort Piccolipiù, using the Infinium Methylation EPIC BeadChip and qPCR, respectively. PM10 daily exposure levels, based on maternal residential address, were estimated for different gestational periods using models based on satellite data. Epigenome-wide analysis to identify differentially methylated probes (DMPs) and regions (DMRs) was conducted, followed by a pathway analysis and replication analysis in an second Piccolipiù dataset. Distributed lag models (DLMs) using weekly exposures were used to study the association of PM10 exposure across pregnancy with telomere length, as well as with the DMPs that showed robust associations. RESULTS: Gestational PM10 exposure was associated with the DNA methylation of more than 250 unique DMPs, most of them identified in early gestation, and 1 DMR. Out of 151 DMPs available in the replication dataset, ten DMPs showed robust associations: eight were associated with exposure during early gestation and 2 with exposure during the whole pregnancy. These exposure windows were supported by the DLM analysis. The PM10 exposure between 15th and 20th gestational week seem to be associated with shorter telomeres at birth, while exposure between 24th and 29th was associated with longer telomeres. DISCUSSION: The early pregnancy period is a potential critical window during which PM10 exposure can influence cord blood DNA methylation. The results from the TL analysis were consistent with previous findings and merit further exploration in future studies. The study underlines the importance of considering gestational windows outside of the predefined trimesters that may not always overlap with biologically relevant windows of exposure.

Variations in Neonatal Length of Stay of Babies Born Extremely Preterm: An International Comparison Between iNeo Networks.

OBJECTIVE: To compare length of stay (LOS) in neonatal care for babies born extremely preterm admitted to networks participating in the International Network for Evaluating Outcomes of Neonates (iNeo). STUDY DESIGN: Data were extracted for babies admitted from 2014 to 2016 and born at 24 to 28 weeks of gestational age (n = 28 204). Median LOS was calculated for each network for babies who survived and those who died while in neonatal care. A linear regression model was used to investigate differences in LOS between networks after adjusting for gestational age, birth weight z score, sex, and multiplicity. A sensitivity analysis was conducted for babies who were discharged home directly. RESULTS: Observed median LOS for babies who survived was longest in Japan (107 days); this result persisted after adjustment (20.7 days more than reference, 95% CI 19.3-22.1). Finland had the shortest adjusted LOS (-4.8 days less than reference, 95% CI -7.3 to -2.3). For each week's increase in gestational age at birth, LOS decreased by 12.1 days (95% CI -12.3 to -11.9). Multiplicity and male sex predicted mean increases in LOS of 2.6 (95% CI 2.0-3.2) and 2.1 (95% CI 1.6-2.6) days, respectively. CONCLUSIONS: We identified between-network differences in LOS of up to 3 weeks for babies born extremely preterm. Some of these may be partly explained by differences in mortality, but unexplained variations also may be related to differences in clinical care practices and healthcare systems between countries.

Exposure to ambient air pollution in the first 1000 days of life and alterations in the DNA methylome and telomere length in children: A systematic review.

BACKGROUND: Exposure to air pollution during the first 1000 days of life (from conception to the 2nd year of life) might be of particular relevance for long-term child health. Changes in molecular markers such as DNA methylation and telomere length could underlie the association between air pollution exposure and pollution-related diseases as well as serve as biomarkers for past exposure. The objective of this systematic review was to assess the association between air pollution exposure during pregnancy and the first two years of life and changes in DNA methylation or telomere length in children. METHODS: PubMed was searched in October 2020 by using terms relative to ambient air pollution exposure, DNA methylation, telomere length and the population of interest: mother/child dyads and children. Screening and selection of the articles was completed independently by two reviewers. Thirty-two articles matched our criteria. The majority of the articles focused on gestational air pollution exposure and measured DNA methylation/telomere length in newborn cord blood or placental tissue, to study global, candidate-gene or epigenome-wide methylation patterns and/or telomere length. The number of studies in children was limited. RESULTS: Ambient air pollution exposure during pregnancy was associated with global loss of methylation in newborn cord blood and placenta, indicating the beginning of the pregnancy as a potential period of susceptibility. Candidate gene and epigenome-wide association studies provided evidence that gestational exposure to air pollutants can lead to locus-specific changes in methylation, in newborn cord blood and placenta, particularly in genes involved in cellular responses to oxidative stress, mitochondrial function, inflammation, growth and early life development. Telomere length shortening in newborns and children was seen in relation to gestational pollutant exposure. CONCLUSIONS: Ambient air pollution during pregnancy is associated with changes in both global and locus-specific DNA methylation and with telomere length shortening. Future studies need to test the robustness of the association across different populations, to explore potential windows of vulnerability and assess the role of the methylation and telomere length as mediators in the association between early exposure to ambient air pollutants and specific childhood health outcomes.

The first 1000 days of life: traffic-related air pollution and development of wheezing and asthma in childhood. A systematic review of birth cohort studies.

BACKGROUND: The first 1000 days of life -including pregnancy and the first 2 years after birth- represent a critical window for health interventions. This systematic review aimed to summarize the evidence on the relationship between traffic-related air pollutants exposure in the first 1000 days of life and the development of wheezing and asthma, with a particular focus on windows of exposure. METHODS: Medline and Embase were searched from January 2000 to May 2020 to retrieve population-based birth-cohort studies, including registries, providing quantitative information on the association between exposure to traffic-related air pollutants during pregnancy or early life, and the risk of developing wheezing and asthma in childhood. Screening and selection of the articles were completed independently by three reviewers. The quality of studies was assessed using the Newcastle-Ottawa scale. RESULTS: Out of 9681 records retrieved, 26 studies from 21 cohorts were included. The most common traffic-related air pollutant markers were particulate matter (PM) and nitric oxides (NOx). The variability in terms of pollutants, exposure assessment methods, and exposure levels chosen to present the results did not allow a meta-analysis. Exposure to PM and NOx in pregnancy (10 cohorts) was consistently associated with an increased risk of asthma development, while the association with wheezing development was unclear. The second trimester of pregnancy seemed to be particularly critical for asthma risk. As for exposure during early life (15 cohorts), most studies found a positive association between PM (7/10 studies) and NOx (11/13 studies) and the risk of asthma development, while the risk of wheezing development was controversial. The period of postnatal exposure, however, was less precisely defined and a partial overlap between the period of exposure measurement and that of outcome development was present in a consistent number of studies (14 out of 15) raising doubts on the associations found. CONCLUSIONS: Traffic-related air pollution during pregnancy is associated with an increased risk of asthma development among children and adolescents. The relationship between exposure in the first two years of life and the development of wheezing and asthma needs to be confirmed in studies with more precise exposure assessment.

Delayed presentation of children to the emergency department during the first wave of COVID-19 pandemic in Italy: Area-based cohort study.

AIM: To ascertain a delay in attendances to the emergency department (ED) during 2020 lockdown. METHODS: Area-based cohort study on paediatric (0-15 years) attendances resulting in hospital admission in Tuscany, Italy, in February-May 2020, and the corresponding periods in 2018-19. We analysed times from symptom onset to arrival, the odds of arriving late (>90th centile of time) and paediatricians' judgements of a late presentation by logistic models. RESULTS: As expected, ED attendance fell sharply (-62%) in 2020 vs 2018-19. As for cases studied (455 in 2020 and 1161 in 2018-19), we documented a delay in arrival to the ED in 2020 versus 2018-19 for several groups of diagnoses, namely gastroenteritis, sepsis, wounds, burns and infections overall. Time to presentation over 90th centile was also higher in 2020 (odds ratio, OR: 1.44; 95% confidence interval: 1.00, 2.06), as were paediatricians' judgements of a late arrival (18.9% of cases in 2020 vs. 13.4% in 2018-19; OR: 1.58; 1.14, 2.19) CONCLUSION: In a population-based cohort, delayed attendances to ED ascertained both subjectively and objectively convey the message to families and to paediatricians to seek hospital care in case of severe or unremitting symptoms and not to wait longer than they normally would.

COVID-19-like symptoms and their relation to the SARS-CoV-2 epidemic in children and adults of an Italian birth cohort

OBJECTIVES: to estimate the population prevalence of COVID-19-like symptoms in children and adults during the first SARS-CoV-2 epidemic wave hitting Italy in the spring 2020; to assess their geographical correlation with the cumulative number of COVID-19 cases by province; to analyse their clustering within families; to estimate their sensitivity, positive predictive value (PPV) and negative predictive value (NPV) for COVID-19 diagnosis in individuals tested for SARS-CoV-2. DESIGN: cross-sectional study nested within a birth cohort. SETTING AND PARTICIPANTS: mothers participating in an Italian birth cohort (NINFEA) were invited to complete an online questionnaire on COVID-19-like symptoms in their household. MAIN OUTCOME MEASURES: population prevalence of COVID-19-like symptoms in children and adults, geographical correlation of COVID-19-like symptoms with the cumulative number of COVID-19 cases by province, clustering of COVID-19-like symptoms within families, and sensitivity, PPV and NPV of COVID-19-like symptoms for COVID-19 diagnosis in individuals tested for SARS-CoV-2. RESULTS: information was collected on 3,184 households, 6,133 adults, and 5,751 children. In the period March-April 2020, 55.4% of the NINFEA families had at least one member with at least one COVID-19-like symptom. There was a strong geographical correlation between the population cumulative incidence of COVID-19 and the prevalence of muscle pain, fatigue, low-grade fever, and breathing difficulties in adults (Spearman's rho >=0.70). Having at least one family member with a COVID-19 diagnosis, compared with none tested for SARS-CoV-2, was associated with an increased prevalence ratio (PR) of almost all COVID-19-like symptoms in adults, and only of low-grade fever (37-37.5°C; PR 4.54; 95%CI 2.20-9.40) and anosmia/dysgeusia in children. Among adults with COVID-19 diagnosis, fatigue, muscle pain, and fever had a sensitivity >=70%. In individuals tested for SARS-CoV-2, with a 16.6% prevalence of COVID-19, breathing difficulties and nausea/vomiting had the highest PPVs, with point estimates close to 60%, and with NPVs close to 90%. CONCLUSIONS: the geographical prevalence of COVID-19-like symptoms in adults may inform on local disease clusters, while certain symptoms in family members of confirmed COVID-19 cases could help identify the intra-familial spread of the virus and its further propagation in the community. Low-grade fever is frequent in children with at least one household member with COVID-19 and possibly indicates child infection.

Socioeconomic inequalities in reproductive outcomes in the Italian NINFEA birth cohort and the Piedmont Birth Registry.

BACKGROUND: socioeconomic inequalities in reproductive outcomes have been consistently reported in several countries. In a European collaborative study conducted in 2012 whose aim was to investigate the association between socioeconomic position (SEP), measured through maternal education, and preterm delivery inconsistent results were found for the NINFEA birth cohort. However, NINFEA contributed to that study with the first 2,500 pregnancies only, and estimates were not adjusted for any potential confounders assuming that SEP is a distal exposure, that could not be affected by other preterm risk factors. OBJECTIVES: to investigate the relationship between SEP and the reproductive outcomes using the entire NINFEA cohort and compare the results with the population-based Piedmont Birth Registry (PBR), accounting for potential baseline collider bias both in the cohort and in the registry. DESIGN: observational study. SETTING AND PARTICPANTS: 5,323 NINFEA singletons, whose mothers registered into the study before the 36th week of gestation, were analysed. Analyses on maternal education were replicated in the 2011 PBR of 35,318 singletons live births. Factors affecting the likelihood of being a member of the NINFEA study or becoming pregnant in the general population were treated as potential confounders to adjust for baseline collider bias. MAIN OUTCOME MEASURES: the association of maternal education and a recently developed household income indicator with both preterm delivery (<37th weeks of gestation) and low birth weight (<2,500 gr) were analysed. RESULTS: in the NINFEA cohort, low SEP was positively associated with both preterm delivery and low birth weight, with slightly stronger associations for household income, especially on low birth weight. Results were consistent with those obtained in the PBR data, where an inverse relationship between maternal education and the two reproductive outcomes was found. In both populations, there was confounding due to maternal age and parity, showing that independently of the nature of the source population, baseline factors that affect the probability of being a member of such source population have to be accounted for to allow causal inference. CONCLUSIONS: low SEP is associated with adverse reproductive outcomes in a contemporary Italian population.

Factors associated with self-perceived knowledge of COVID-19: a study among women from the NINFEA birth cohort.

BACKGROUND: health literacy may contribute to the strategies to control the Coronavirus disease 2019 (COVID-19), as individuals need to acquire promptly new health information, understand the reasons behind recommendations, and adapt their behaviour accordingly. OBJECTIVES: to investigate sociodemographic and disease-related factors that can influence self-perceived knowledge (poor/medium vs high) about COVID-19 in women of the Italian NINFEA birth cohort. DESIGN: cross-sectional study. SETTING AND PARTICIPANTS: a web-based anonymous survey on COVID-19 was sent in April 2020 to women participating in the NINFEA cohort. A total of 3,129 women were included in the study. MAIN OUTCOME MEASURES: using multiple weighted logistic regression models, self-perceived knowledge level was analysed in relation with the following variables: age, education level, family size, cumulative incidence of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) cases until 7 April 2020 by province, presence of COVID-19-like symptoms, SARS-CoV-2 testing, and COVID-19 diagnosis. RESULTS: the prevalence of self-perceived poor/medium knowledge was 57%. In multivariable logistic regression analyses, the odds ratio (OR) of self-perceived poor/medium COVID-19 knowledge level was increased for low/medium compared with high education level (OR 1.57; 95%CI 1.34-1.84), and decreased for SARS-CoV-2 testing (OR 0.25; 95%CI 0.16-0.39) and COVID-19 diagnosis (OR 0.20; 95%CI 0.07-0.60). There was no evidence of association between the other analysed variables and self-perceived knowledge level. CONCLUSIONS: the findings of this study suggest that low educational level is a determinant of low self-perceived knowledge on COVID-19 in middle-aged women.

Trends in Outcomes for Neonates Born Very Preterm and Very Low Birth Weight in 11 High-Income Countries.

OBJECTIVE: To evaluate outcome trends of neonates born very preterm in 11 high-income countries participating in the International Network for Evaluating Outcomes of neonates. STUDY DESIGN: In a retrospective cohort study, we included 154 233 neonates admitted to 529 neonatal units between January 1, 2007, and December 31, 2015, at 240/7 to 316/7 weeks of gestational age and birth weight <1500 g. Composite outcomes were in-hospital mortality or any of severe neurologic injury, treated retinopathy of prematurity, and bronchopulmonary dysplasia (BPD); and same composite outcome excluding BPD. Secondary outcomes were mortality and individual morbidities. For each country, annual outcome trends and adjusted relative risks comparing epoch 2 (2012-2015) to epoch 1 (2007-2011) were analyzed. RESULTS: For composite outcome including BPD, the trend decreased in Canada and Israel but increased in Australia and New Zealand, Japan, Spain, Sweden, and the United Kingdom. For composite outcome excluding BPD, the trend decreased in all countries except Spain, Sweden, Tuscany, and the United Kingdom. The risk of composite outcome was lower in epoch 2 than epoch 1 in Canada (adjusted relative risks 0.78; 95% CI 0.74-0.82) only. The risk of composite outcome excluding BPD was significantly lower in epoch 2 compared with epoch 1 in Australia and New Zealand, Canada, Finland, Japan, and Switzerland. Mortality rates reduced in most countries in epoch 2. BPD rates increased significantly in all countries except Canada, Israel, Finland, and Tuscany. CONCLUSIONS: In most countries, mortality decreased whereas BPD increased for neonates born very preterm.

Perinatal maternal mental health is associated with both infections and wheezing in early childhood.

BACKGROUND: Wheezing and infections are common during infancy, and the role of early-life exposures in their development is still under investigation. We examined associations between maternal mental health in pregnancy and after delivery and subsequent offspring wheezing and infections. METHODS: We studied 2314 mother-child pairs recruited in the Piccolipiù birth cohort (Italy) from 2011 to 2015. Maternal mental health was assessed in pregnancy and 12 months after delivery via the General Health Questionnaire-12 (GHQ-12). GHQ-12 Likert scores were collapsed into low (below the upper tercile) and high (above). Risk ratios (RR) and 95% confidence intervals (CI) between each combination of scores-during pregnancy and 1 year after delivery-and outcomes were computed by log-binomial regression models. RESULTS: High scores both in pregnancy and after delivery, compared with low scores in both periods, were associated with wheezing (RR: 1.35; 95% CI: 1.08, 1.69), recurrent (≥2 episodes) wheezing (1.35; 0.99, 1.83), any and recurrent (≥4 episodes) upper respiratory infections (1.20; 1.04, 1.41, and 1.45; 1.07, 1.97, respectively), lower respiratory infections (1.31; 1.08, 1.61), and diarrhea (1.49; 1.23, 1.80). High scores either during pregnancy or 1 year after delivery only were less consistently associated with outcomes. CONCLUSIONS: Maternal mental health problems extending from pregnancy to the first year after delivery are associated with development of both wheezing and infections. As wheezing is mostly triggered by infections, increased infection susceptibility could represent a possible common biologic mechanism. This study confirms the importance of early-life exposures on childhood health.

Differentially methylated DNA regions in early childhood wheezing: An epigenome-wide study using saliva.

BACKGROUND: Epigenetics may play a role in wheezing and asthma development. We aimed to examine infant saliva DNA methylation in association with early childhood wheezing. METHODS: A case-control study was nested within the NINFEA birth cohort with 68 cases matched to 68 controls by sex, age (between 6 and 18 months, median: 10.3 months) and season at saliva sampling. Using a bumphunting region-based approach, we examined associations between saliva methylome measured using Illumina Infinium HumanMethylation450k array and wheezing between 6 and 18 months of age. We tested our main findings in independent publicly available data sets of childhood respiratory allergy and atopic asthma, with DNA methylation measured in different tissues and at different ages. RESULTS: We identified one wheezing-associated differentially methylated region (DMR) spanning ten sequential CpG sites in the promoter-regulatory region of PM20D1 gene (family-wise error rate < 0.05). The observed associations were enhanced in children born to atopic mothers. In the publicly available data sets, hypermethylation in the same region of PM20D1 was consistently found at different ages and in all analysed tissues (cord blood, blood, saliva and nasal epithelia) of children with respiratory allergy/atopic asthma compared with controls. CONCLUSION: This study suggests that PM20D1 hypermethylation is associated with early childhood wheezing. Directionally consistent epigenetic alteration observed in cord blood and other tissues at older ages in children with respiratory allergy and atopic asthma provides suggestive evidence that a long-term epigenetic modification, likely operating from birth, may be involved in childhood atopic phenotypes.