Association of Assisted Reproductive Technology With Offspring Growth and Adiposity From Infancy to Early Adulthood.

Importance: People conceived using assisted reproductive technology (ART) make up an increasing proportion of the world's population. Objective: To investigate the association of ART conception with offspring growth and adiposity from infancy to early adulthood in a large multicohort study. Design, Setting, and Participants: This cohort study used a prespecified coordinated analysis across 26 European, Asia-Pacific, and North American population-based cohort studies that included people born between 1984 and 2018, with mean ages at assessment of growth and adiposity outcomes from 0.6 months to 27.4 years. Data were analyzed between November 2019 and February 2022. Exposures: Conception by ART (mostly in vitro fertilization, intracytoplasmic sperm injection, and embryo transfer) vs natural conception (NC; without any medically assisted reproduction). Main Outcomes and Measures: The main outcomes were length / height, weight, and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared). Each cohort was analyzed separately with adjustment for maternal BMI, age, smoking, education, parity, and ethnicity and offspring sex and age. Results were combined in random effects meta-analysis for 13 age groups. Results: Up to 158 066 offspring (4329 conceived by ART) were included in each age-group meta-analysis, with between 47.6% to 60.6% females in each cohort. Compared with offspring who were NC, offspring conceived via ART were shorter, lighter, and thinner from infancy to early adolescence, with differences largest at the youngest ages and attenuating with older child age. For example, adjusted mean differences in offspring weight were -0.27 (95% CI, -0.39 to -0.16) SD units at age younger than 3 months, -0.16 (95% CI, -0.22 to -0.09) SD units at age 17 to 23 months, -0.07 (95% CI, -0.10 to -0.04) SD units at age 6 to 9 years, and -0.02 (95% CI, -0.15 to 0.12) SD units at age 14 to 17 years. Smaller offspring size was limited to individuals conceived by fresh but not frozen embryo transfer compared with those who were NC (eg, difference in weight at age 4 to 5 years was -0.14 [95% CI, -0.20 to -0.07] SD units for fresh embryo transfer vs NC and 0.00 [95% CI, -0.15 to 0.15] SD units for frozen embryo transfer vs NC). More marked differences were seen for body fat measurements, and there was imprecise evidence that offspring conceived by ART developed greater adiposity by early adulthood (eg, ART vs NC difference in fat mass index at age older than 17 years: 0.23 [95% CI, -0.04 to 0.50] SD units). Conclusions and Relevance: These findings suggest that people conceiving or conceived by ART can be reassured that differences in early growth and adiposity are small and no longer evident by late adolescence.

[Impact of the COVID-19 epidemic on total and cause-specific mortality in Rome (Italy) in 2020]. / Impatto dell'epidemia di COVID-19 sulla mortalità totale e per causa a Roma nel 2020.

OBJECTIVES: to estimate the impact of the COVID-19 epidemic on total and cause-specific mortality in people residing and dead in the Municipality of Rome (Italy) in 2020, and to describe the causes of death of subjects with SARS-CoV-2 infection confirmed by molecular test. DESIGN: descriptive analysis of total and cause-specific mortality in 2020 in Rome and comparison with a reference period (2015-2018 for total mortality and 2018 for cause-specific mortality); descriptive analysis of cause-specific mortality in the cohort of SARS-CoV-2 infected subjects. SETTING AND PARTICIPANTS: 27,471 deaths registered in the Lazio mortality-cause Registry, relating to people residing and died in the municipality of Rome in 2020, 2,374 of which died from COVID-19.MAIN OUCOME MEASURES: all-cause mortality by month, gender, age group and place of death, cause-specific mortality (ICD-10 codes). RESULTS: in the municipality of Rome in 2020, an excess of mortality from all causes equal to +10% was observed, with a greater increase in the months of October-December (+27%, +56%, and +26%, respectively) in people aged 50+, with the greatest contribution from the oldest age groups (80+) who died in the nursing homes or at home. Lower mortality was observed in the age groups 0-29 years (-30%) and 40-49 years (-13%). In 2020, COVID-19 represents the fourth cause of death in Rome after malignant tumours, diseases of the circulatory system, and respiratory diseases. Excess mortality was observed from stroke and pneumonia (both in men and women), from respiratory diseases (in men), from diabetes, mental disorders, dementia and Parkinson's disease (in women). On the contrary, mortality is lower for all cancers, for diseases of the blood and haematopoietic organs and for the causes of the circulatory system. The follow-up analysis of SARS-CoV-2 positive subjects residing in Rome shows that a share of deaths (about 20%) reports other causes of death such as cardiovascular diseases, malignant tumours, and diseases of the respiratory system on the certificate collected by the Italian National Statistics Institute. CONCLUSIONS: the 2020 mortality study highlighted excesses for acute and chronic pathologies, indicative of possible delays in the diagnosis or treatment of conditions indirectly caused by the pandemic, but also a share of misclassification of the cause of death that is recognized as COVID-19 death.

Modifiable environmental factors predispose term infants to bronchiolitis but bronchiolitis itself predisposes to respiratory sequelae.

INTRODUCTION: Viral bronchiolitis is a common lower respiratory tract infection in infants. Environmental and genetic factors can favor respiratory tract infections. AIM: The aim of this study is to analyze risk factors for bronchiolitis and to investigate the predisposing factors for developing transient wheezing and asthma through a 6-year follow-up after hospitalization for bronchiolitis compared with a group of healthy controls that belonged to Piccolipiù cohort, who never had bronchiolitis. METHODS: We enrolled 645 infants hospitalized with bronchiolitis. A structured questionnaire was used to obtain demographic and clinical data. At 6 years of age, 370 cases and 183 controls were investigated for the presence of asthma by the structured questionnaire, for prick test and for spirometry, and were classified to asthmatic, transient wheezing, and no wheezing/no asthma. RESULTS: Breastfeeding was an independent protective factor (odds ratio [OR]: 0.3, 95% confidence interval [95% CI]: 0.2-0.4, p < 0.001) and tobacco smoke was a risk factor for the development of bronchiolitis (OR: 2.1, 95% CI: 1.4-3.1, p < 0.001). Analyzing follow-up, bronchiolitis increased the risk of developing transient wheezing by 12.9 (95% CI: 6.3-26.1, p < 0.001) and of developing asthma by 4.6 (95% CI: 1.9-10.7, p < 0.001). A positive family history of atopy increased the risk of developing asthma by 3.1 (95% CI: 1.4-6.7, p = 0.005). Asthmatic patients had a lower % FEV1, a lower % flow-volume curve (FVC), and a lower FEV1/FVC value, and they had more frequently positive skin prick test. CONCLUSION: Bronchiolitis is influenced by environmental factors: tobacco smoke increases its risk and breastfeeding is a protective factor. At the end of 6 years of follow-up, bronchiolitis is a significant risk factor to have pre-school wheezing and asthma.

Mother's education and offspring asthma risk in 10 European cohort studies.

Highly prevalent and typically beginning in childhood, asthma is a burdensome disease, yet the risk factors for this condition are not clarified. To enhance understanding, this study assessed the cohort-specific and pooled risk of maternal education on asthma in children aged 3-8 across 10 European countries. Data on 47,099 children were obtained from prospective birth cohort studies across 10 European countries. We calculated cohort-specific prevalence difference in asthma outcomes using the relative index of inequality (RII) and slope index of inequality (SII). Results from all countries were pooled using random-effects meta-analysis procedures to obtain mean RII and SII scores at the European level. Final models were adjusted for child sex, smoking during pregnancy, parity, mother's age and ethnicity. The higher the score the greater the magnitude of relative (RII, reference 1) and absolute (SII, reference 0) inequity. The pooled RII estimate for asthma risk across all cohorts was 1.46 (95% CI 1.26, 1.71) and the pooled SII estimate was 1.90 (95% CI 0.26, 3.54). Of the countries examined, France, the United Kingdom and the Netherlands had the highest prevalence's of childhood asthma and the largest inequity in asthma risk. Smaller inverse associations were noted for all other countries except Italy, which presented contradictory scores, but with small effect sizes. Tests for heterogeneity yielded significant results for SII scores. Overall, offspring of mothers with a low level of education had an increased relative and absolute risk of asthma compared to offspring of high-educated mothers.

Variations in the prevalence of childhood asthma and wheeze in MeDALL cohorts in Europe.

While there is evidence for variations in prevalence rates of childhood wheeze and asthma between countries, longitudinal, individual-level data are needed to understand these differences. The aim of this study was to examine variations in prevalence rates of childhood asthma, wheeze and wheeze with asthma in Europe. We analysed datasets from 10 MeDALL (Mechanisms of the Development of ALLergy) cohorts in eight countries, representing 26 663 children, to calculate prevalence rates of wheeze and asthma by child age and wheeze with asthma at age 4 years. Harmonised variables included outcomes parent-reported wheeze and parent-reported doctor-diagnosed asthma, and covariates maternal education, parental smoking, pets, parental asthma, doctor-diagnosed allergic rhinitis, doctor-diagnosed eczema and wheeze severity. At age 4 years, asthma prevalence varied from 1.72% in Germany to 13.48% in England and the prevalence of wheeze varied from 9.82% in Greece to 55.37% in Spain. Adjusted estimates of the proportion of 4-year-old children with wheeze diagnosed with asthma remained highest in England (38.14%, 95% CI 31.38-44.90%) and lowest in Spain (15.94%, 95% CI 6.16-25.71%). The large differences in prevalence rates of asthma, wheeze and wheeze with asthma at age 4 years between European cohorts may indicate that childhood asthma is more readily diagnosed in some countries while going unrecognised elsewhere.

Air Pollution and Cognitive Development at Age 7 in a Prospective Italian Birth Cohort.

BACKGROUND: Early life exposure to air pollution has been linked with cognitive impairment in children, but the results have not been conclusive. We analyzed the association between traffic-related air pollution and cognitive function in a prospective birth cohort in Rome. METHODS: A cohort of 719 newborns was enrolled in 2003-2004 as part of the GASPII project. At age 7 years, 474 children took the Wechsler Intelligence Scale for Children-III to assess their cognitive development in terms of IQ composite scores. Exposure to air pollutants (NO2, PMcoarse, PM2.5, PM2.5 absorbance) at birth was assessed using land use regression models. We also considered variables indicating traffic intensity. The effect of environmental pollution on IQ was evaluated performing a linear regression model for each outcome, adjusting for gender, child age at cognitive test, maternal age at delivery, parental educational level, siblings, socio-economic status, maternal smoking during pregnancy, and tester. To account for selection bias at enrollment and during follow-up, the regression models were weighted for the inverse probabilities of participation and follow-up. RESULTS: A 10 µg/m³ higher NO2 exposure during pregnancy was associated with 1.4 fewer points (95% confidence interval = -2.6, -0.20) of verbal IQ, and 1.4 fewer points (95% confidence interval = -2.7, -0.20) of verbal comprehension IQ. Similar associations were found for traffic intensity in a 100 m buffer around home. Other pollutants showed negative associations with larger confidence intervals. CONCLUSIONS: Consistent with previous evidence, this study suggests an association of exposure to NO2 and traffic intensity with the verbal area of cognitive development.See Video Abstract at http://links.lww.com/EDE/B12.

[Epidemiologic studies on the health status of the population living in the Sacco River Valley]. / Indagini epidemiologiche sullo stato di salute della popolazione residente nell'area della Valle del Sacco.

UNLABELLED: OBIETTIVO: to analyze the health status of the population living in an area close to the Colleferro industrial plant. SETTING AND PARTICIPANTS: the area of the Sacco River Valley, Central Italy nearby Rome, has been heavily polluted over the years by industrial wastes deriving from the chemical industrial plant in Colleferro. In 2006, it was discovered that the herds of livestock were contaminated by beta-hexachlorocycloexane (ß-HCH, an industrial waste belonging, as well as lindane, to the group of hexachlorocycloexane isomers). MAIN OUTCOME MEASURES: the analyses of mortality and morbidity were carried out for the 1998-2007 period (calculation of standardized mortality ratios, SMR), and for the period 2003-2007 (calculation of standardized hospitalization ratios, SHR), respectively. The general population in the Lazio Region has been considered as reference. In addition, a biomonitoring study was conducted on a sample of the population living in 4 areas of the Sacco River Valley with different levels of exposure and the following persistent organic pollutants were measured in the blood (α, ß and γ-HCH, HCB p,p'-DDT and p,p'- DDE, 6 NDL-PCB congeners and 12 DL-PCBs, PCDDs and PCDFs), and heavy metals (Cd, Hg, Pb). RESULTS: cancer mortality in men was increased in the area (SMR=1.20), especially for specific cancer sites (stomach, larynx, lungs, pleura, myeloma); in women an excess of mortality from diabetes was detected (SMR=1.44). The analysis of morbidity indicated an excess of hospitalization for various cancers (larynx, myeloma) in men, for respiratory illness and asthma in both genders and for thyroid disease in women. The biomonitoring study found high mean concentration of ß-HCH (mean: 99.05 ng/g fat, SD=121.3), with higher levels in the population living along the river (mean=150 ng/g fat; SD=153.5), likely occurred through water and local food. CONCLUSION: the area of Colleferro has been polluted by multiple sources and the human population has been exposed to industrial chemicals, toxic substances in the workplace, and to the cumulative accumulation of organic pesticides especially through water and food.

European birth cohorts for environmental health research.

BACKGROUND: Many pregnancy and birth cohort studies investigate the health effects of early-life environmental contaminant exposure. An overview of existing studies and their data is needed to improve collaboration, harmonization, and future project planning. OBJECTIVES: Our goal was to create a comprehensive overview of European birth cohorts with environmental exposure data. METHODS: Birth cohort studies were included if they a) collected data on at least one environmental exposure, b) started enrollment during pregnancy or at birth, c) included at least one follow-up point after birth, d) included at least 200 mother-child pairs, and e) were based in a European country. A questionnaire collected information on basic protocol details and exposure and health outcome assessments, including specific contaminants, methods and samples, timing, and number of subjects. A full inventory can be searched on www.birthcohortsenrieco.net. RESULTS: Questionnaires were completed by 37 cohort studies of > 350,000 mother-child pairs in 19 European countries. Only three cohorts did not participate. All cohorts collected biological specimens of children or parents. Many cohorts collected information on passive smoking (n = 36), maternal occupation (n = 33), outdoor air pollution (n = 27), and allergens/biological organisms (n = 27). Fewer cohorts (n = 12-19) collected information on water contamination, ionizing or nonionizing radiation exposures, noise, metals, persistent organic pollutants, or other pollutants. All cohorts have information on birth outcomes; nearly all on asthma, allergies, childhood growth and obesity; and 26 collected information on child neurodevelopment. CONCLUSION: Combining forces in this field will yield more efficient and conclusive studies and ultimately improve causal inference. This impressive resource of existing birth cohort data could form the basis for longer-term and worldwide coordination of research on environment and child health.

Health impact assessment of waste management facilities in three European countries.

BACKGROUND: Policies on waste disposal in Europe are heterogeneous and rapidly changing, with potential health implications that are largely unknown. We conducted a health impact assessment of landfilling and incineration in three European countries: Italy, Slovakia and England. METHODS: A total of 49 (Italy), 2 (Slovakia), and 11 (England) incinerators were operating in 2001 while for landfills the figures were 619, 121 and 232, respectively. The study population consisted of residents living within 3 km of an incinerator and 2 km of a landfill. Excess risk estimates from epidemiological studies were used, combined with air pollution dispersion modelling for particulate matter (PM10) and nitrogen dioxide (NO2). For incinerators, we estimated attributable cancer incidence and years of life lost (YoLL), while for landfills we estimated attributable cases of congenital anomalies and low birth weight infants. RESULTS: About 1,000,000, 16,000, and 1,200,000 subjects lived close to incinerators in Italy, Slovakia and England, respectively. The additional contribution to NO2 levels within a 3 km radius was 0.23, 0.15, and 0.14 µg/m3, respectively. Lower values were found for PM10. Assuming that the incinerators continue to operate until 2020, we are moderately confident that the annual number of cancer cases due to exposure in 2001-2020 will reach 11, 0, and 7 in 2020 and then decline to 0 in the three countries in 2050. We are moderately confident that by 2050, the attributable impact on the 2001 cohort of residents will be 3,621 (Italy), 37 (Slovakia) and 3,966 (England) YoLL. The total exposed population to landfills was 1,350,000, 329,000, and 1,425,000 subjects, respectively. We are moderately confident that the annual additional cases of congenital anomalies up to 2030 will be approximately 2, 2, and 3 whereas there will be 42, 13, and 59 additional low-birth weight newborns, respectively. CONCLUSIONS: The current health impacts of landfilling and incineration can be characterized as moderate when compared to other sources of environmental pollution, e.g. traffic or industrial emissions, that have an impact on public health. There are several uncertainties and critical assumptions in the assessment model, but it provides insight into the relative health impact attributable to waste management.

Systematic review of epidemiological studies on health effects associated with management of solid waste.

BACKGROUND: Management of solid waste (mainly landfills and incineration) releases a number of toxic substances, most in small quantities and at extremely low levels. Because of the wide range of pollutants, the different pathways of exposure, long-term low-level exposure, and the potential for synergism among the pollutants, concerns remain about potential health effects but there are many uncertainties involved in the assessment. Our aim was to systematically review the available epidemiological literature on the health effects in the vicinity of landfills and incinerators and among workers at waste processing plants to derive usable excess risk estimates for health impact assessment. METHODS: We examined the published, peer-reviewed literature addressing health effects of waste management between 1983 and 2008. For each paper, we examined the study design and assessed potential biases in the effect estimates. We evaluated the overall evidence and graded the associated uncertainties. RESULTS: In most cases the overall evidence was inadequate to establish a relationship between a specific waste process and health effects; the evidence from occupational studies was not sufficient to make an overall assessment. For community studies, at least for some processes, there was limited evidence of a causal relationship and a few studies were selected for a quantitative evaluation. In particular, for populations living within two kilometres of landfills there was limited evidence of congenital anomalies and low birth weight with excess risk of 2 percent and 6 percent, respectively. The excess risk tended to be higher when sites dealing with toxic wastes were considered. For populations living within three kilometres of old incinerators, there was limited evidence of an increased risk of cancer, with an estimated excess risk of 3.5 percent. The confidence in the evaluation and in the estimated excess risk tended to be higher for specific cancer forms such as non-Hodgkin's lymphoma and soft tissue sarcoma than for other cancers. CONCLUSIONS: The studies we have reviewed suffer from many limitations due to poor exposure assessment, ecological level of analysis, and lack of information on relevant confounders. With a moderate level confidence, however, we have derived some effect estimates that could be used for health impact assessment of old landfill and incineration plants. The uncertainties surrounding these numbers should be considered carefully when health effects are estimated. It is clear that future research into the health risks of waste management needs to overcome current limitations.

[Enrolment and follow-up of a birth cohort in Rome]. / Arruolamento e follow-up di una coorte di neonati a Roma.

OBJECTIVE: Longitudinal studies on cohorts of babies enrolled at birth are ongoing in Europe. On the basis of these experiences, a birth cohort study should be implemented in Italy at a national level. A pilot study is ongoing in Rome, from which we report data on adherence at recruitment and follow-up. DESIGN: Prospective cohort study. SETTING: the birth cohort was enrolled between June 2003 and October 2004, in two hospital ofRome in the district ofthe Local Health Unit RME. PARTICIPANTS: we enrolled children of women older than 18 years, Italian citizens and residents in the Local Health Unit RME. MAIN OUTCOME MEASURES: Baseline characteristics of enrolled women were compared with those of refusals, and characteristics of children with a complete follow-up with those lost at follow-up. Prevalence Rate ratio (PR) and the relative 95% confidence interval were calculated. RESULTS: The cohort consisted of 704 women (54% of the contacted) and 719 children. A low level of instruction (PR 2.84), and a caesarean delivery (OR 1.41) were significantly associated with the refusal. After the enrolment 25 children were lost, 117 were partially followed-up and 577 had a complete follow-up until the 15 month visit. Mothers of children lost at follow-up were less instructed (PR 1.69) and smoked during pregnancy (PR 1.57). CONCLUSIONS: During the enrolment and the follow-up of a birth cohort greater efforts must be done to avoid selection for the socioeconomic level of the family. Keeping a high response rate to follow-up is the only way to ensure a good level of internal validity.

Effects of parental smoking and level of education on initiation and duration of breastfeeding.

AIM: To evaluate the effects of parental smoking and level of education on the initiation and duration of breastfeeding in a prospective cohort study on mother-infant pairs. METHODS: We studied 543 mother-infant pairs enrolled after delivery at a hospital in Rome. Information about parents' characteristics were obtained from a questionnaire administered in hospital; the outcome of the study was the infant's feeding habits in the preceding 24 h, assessed by telephone every 2 wk. The effects of parental smoking and level of education on initiation and duration of breastfeeding were evaluated through multivariate logistic regression models and time-dependent Cox models. RESULTS: After controlling for confounding factors, we found a negative effect for mothers' smoking both on breastfeeding initiation (odds ratio 2.19, 95% CI 1.05-4.55) and duration (hazard ratio 3.37, 95% CI 1.85-6.13) when at least one parent had a low level of education. CONCLUSION: Our study shows that maternal smoking, particularly when one of the parents has a low level of education, determines a negative effect on the initiation and duration of breastfeeding. Public health policy should promote educational programmes for both parents focused on quitting smoking, which could have positive effects on the initiation and duration of breastfeeding.