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.

A longitudinal study on the effect of obesity upon circulating renin-angiotensin system in normal pregnancy.

BACKGROUND AND AIMS: Obesity is the most common health issue in women of reproductive age, which profoundly affects maternal-fetal health. Despite progress in understanding key inflammatory and metabolic changes, the pathogenesis of the cardiovascular phenotype of obese pregnant women remains to be fully understood. This study aimed at: (i) evaluating the changes of the renin-angiotensin system (RAS) throughout pregnancy in obese vs normal weight (control) women, and (ii) evaluating the presence of any associations between maternal hemodynamic status and RAS changes. METHODS AND RESULTS: Thirty-eight normal weight and nineteen obese pregnant women were included. Clinical assessment, blood samples and maternal hemodynamic evaluation were performed at 12, 20, 30, and 36 weeks, while ultrasound assessment was scheduled at 20, 30, and 36 weeks of gestation. Measurements of sFlt-1, PlGF, Angiotensinogen, Renin, AngII, Ang1-7, ACE and ACE2 were performed by ELISA. Our data show that normotensive obese women had lower placental blood supply, as assessed by UV-Q and UV-Q/EFW, as compared to controls, and significantly higher levels of AngII and AngII/Ang1-7 ratio, which were inversely related to placental blood supply. CONCLUSIONS: Our study shows for the first time that normotensive obese women exhibited a significant progressive increase of AngII and AngII/Ang1-7 throughout pregnancy, which were inversely related to placental blood supply as assessed by UV-Q and UV-Q/EFW. Our data shed light on the early changes in pregnant obese women and suggest that RAS dysregulation is a prerequisite rather than a consequence of hypertensive disorders of pregnancy and other maternal neonatal complications.

[Endometriosis, a participatory study in the Serchio Valley (Tuscany Region, Central Italy): state of the art and perspectives]. / Endometriosi, uno studio partecipato nella Valle del Serchio: stato dell'arte e prospettive.

BACKGROUND: endometriosis is a chronic condition with a significant impact on women's health, featured by endometrial tissue outside the uterine cavity. A limited number of studies have been conducted in the general population, and the true prevalence of endometriosis is unknown for many areas of the country. OBJECTIVES: to better estimate the prevalence of endometriosis in three Italian regions (Friuli Venezia Giulia, Tuscany, Apulia) and to assess the relationship between endometriosis and environmental factors in three participating areas (Trieste, Barga, and Taranto), with a focus on Tuscany Region. DESIGN: implementing a specific epidemiological registry for endometriosis, aimed at estimating the incidence and prevalence data. The registry collected information from hospital discharge records and anatomopathological reports of women residing in the three considered regions, aged 15 years or older. Additionally, the analysis includes the assessment of the spatial distribution of endometriosis at both regional and municipal levels in the three study areas. Further research investigations in these areas involve a multilevel screening of a sample of women of childbearing age. Women who test positive in the initial screening (through a self-administered questionnaire) will have the opportunity to undergo a second level of screening, consisting of a gynecological examination, transvaginal ultrasound, a swab for vaginal microbiome analysis, and the collection of blood and urine samples to assess the presence of polychlorinated biphenyls (PCBs) or heavy metals. The adopted scientific approach is based on post-normal science (PNS) concerning the extended peer community. SETTING AND PARTICIPANTS: women aged 15 years or older residing in the three regions. MAIN OUTCOMES MEASURES: estimating the incidence and prevalence of endometriosis based on data collected from the epidemiological registry. The analysis extends to assessing the spatial distribution of endometriosis at municipal levels in the three areas of interest. RESULTS: the preliminary results of the study allowed for the estimation of the spatial distribution of endometriosis incidence in Tuscany. In particular, it was found that there is variability within the region, with some coastal and North-Western areas showing values 20% higher than the regional average. Cities such as Pisa, Lucca, Livorno, Grosseto, Orbetello, and the Serchio Valley with Barga had a probability of excess risk of more than 90% compared to the regional average. CONCLUSIONS: the study is ongoing and requires the active participation of women living in the region to ensure the completeness and accuracy of the collected data. This research effort represents an important contribution to understanding endometriosis in Tuscany and its possible environmental causes.

Oral ibuprofen versus oral ketorolac for children with moderate and severe acute traumatic pain: a randomized comparative study.

This study is to compare ibuprofen and ketorolac for children with trauma-related acute pain. We conducted a multicentre randomized, double-blind, controlled trial in the Paediatric Emergency Department setting. We enrolled patients aged 8 to 17 who accessed the emergency department for pain related to a limb trauma that occurred in the previous 48 h. At the admission, patients were classified based on numeric rating scale-11 (NRS-11) in moderate (NRS 4-6) and severe (NRS 7-10) pain groups. Each patient was randomized to receive either ibuprofen (10 mg/kg) or ketorolac (0.5 mg/kg) and the placebo of the not given drug in a double dummies design. NRS-11 was asked every 30 min until 2 h after drug and placebo administration. The primary outcome was NRS-11 reduction at 60 min. Among 125 patients with severe pain, NRS-11 reduction after 60 min from drug administration was 2.0 (IQR 1.0-4.0) for ibuprofen and 1.0 (IQR 1.0-3.0) for ketorolac (p = 0.36). Ibuprofen was significantly better, considering secondary outcomes, at 90 min with a lower median of NRS-11 (p 0.008), more patients with NRS-11 less than 4 (p 0.01) and a reduction of pain score of more than 3 NRS-11 points (p 0.01). Among 87 patients with moderate pain, the NRS-11 reduction after 60 min from drug administration was 1.63 (± 1.8) for ibuprofen and 1.8 (± 1.6) for ketorolac, with no statistically significant difference.Conclusions: Oral ibuprofen and ketorolac are similarly effective in children and adolescents with acute traumatic musculoskeletal pain.Trial registration: ClinicalTrial.gov registration number: NCT04133623.

Monitoring gestational weight gain: setting up a regional surveillance system in Italy.

BACKGROUND: In many countries, including Italy, there are few national data on pre-pregnancy Body Mass Index (BMI) and gestational weight gain (GWG), despite these being important predictors of maternal and neonatal health outcomes. This dearth of information makes it difficult to develop and monitor intervention policies to reduce the burden of disease linked to inadequate BMI status and/or GWG in pregnant women. This study describes the setting up and initial implementation of a regional surveillance system on pre-pregnancy BMI and GWG. METHODS: Between 1 January 2017 and 31 December 2018, anthropometric data were collected from all pregnant women accessing public health services in the Friuli Venezia Giulia region (Italy) for first ultrasound check (T1) and at delivery (T2). Anthropometric data collected at T1 (self-reported pre-pregnancy weight and measured weight and height) and T2 (measured weight and self-reported pre-pregnancy weight and height) were compared. RESULTS: The system was able to reach 43.8% of all the women who gave birth in the region, and provided complete data for 6400 women of the 7188 who accessed the services at T1. At the beginning of pregnancy 447 (7.0%) women were underweight, 4297 (67.1%) had normal weight, 1131 (17.7%) were overweight and 525 (8.2%) had obesity. At delivery, 2306 (36.0%) women were within the appropriate weight gain range, while for 2021 (31.6%) weight gain was insufficient and for 2073 (32.4%) excessive. Only minor differences were observed between measured and self-reported anthropometric data. CONCLUSIONS: The surveillance system offers an overview of the weight status of women during pregnancy. About 1/3 of women entered pregnancy with unsatisfactory BMI and 2/3 did not achieve the recommended weight gain. This surveillance system can be an effective tool to guide public health interventions.

Quality of Early Essential Newborn Care in hospitals in Gaza: a pre-intervention and post-intervention study.

BACKGROUND: In 2017, the Ministry of Health in Gaza introduced Early Essential Newborn Care (EENC) as its primary maternal and neonatal care strategy. EENC comprises a package of simple evidence-based interventions that are delivered during labour and delivery, and in the early post-partum period, to prevent or treat the most important causes of morbidity and mortality in newborn babies. Four public maternity hospitals in Gaza, responsible for approximately 75% of all deliveries, began implementation of EENC in June, 2017. Clinical coaching was delivered by national facilitators over 2 days, and targeted all clinical staff in maternity and neonatal units. Subsequently, EENC quality improvement teams were formed to address contextual factors that influence practice. This study aimed to determine whether introduction of EENC resulted in changes in clinical practices for vaginal births. METHODS: A pre-intervention and post-intervention design was used to review key clinical practices before and after EENC introduction in the four hospitals. Trained data collection staff visited each hospital for 1 day in each of the months of March and June, 2017 (before EENC implementation), January and April, 2018 (in the early stages of EENC implementation), September, 2018, and June, 2019 (after full EENC implementation). Standard WHO data collection methods and tools were used to gather practice data using exit interviews and chart reviews of 10-15 randomly selected post-partum mothers who had delivered vaginally in the previous 2-24 h and had not experienced a newborn death or stillbirth. Delivery observations were conducted for five to ten randomly selected vaginal deliveries using a standard clinical skills observation checklist, beginning at the second stage of labour. The Ministry of Health in Gaza approved EENC assessments for programme use, and informed verbal consent was obtained before maternal interviews. No personal identifiers were used in assessments. FINDINGS: 259 maternal post-partum interviews and 139 observations of birth practices were done across the four maternity hospitals, representing 8·8% (259 of 2940) and 4·7% (139) of expected vaginal births during the observation periods, respectively. Comparing practices at baseline, early implementation, and after full implementation, significant trend improvements were noted for proportion of babies receiving thorough drying (0% [0 of 12], 49% [32 of 66], 72% [43 of 60], respectively, p<0·0004), immediate skin-to-skin contact (SSC) for less than 1 min (0% [0 of 14], 33% [43 of 127], 66% [72 of 110], p<0·0001), uninterrupted SSC for at least 60 min (0% [0 of 14], 21% [27 of 129], 48% [53 of 111], p<0·0001), uninterrupted SSC for at least 90 min (0% [0 of 14], 10% [13 of 129], 36% [39 of 110], p<0·0001), early breastfeeding (15-90 min after birth) (0% [0 of 15], 39% [50 of 130], 61% [65 of 107], p<0·0001), breastfeeding before separation (0% [0 of 15], 28% [36 of 131], 52% [56 of 108], p<0·0001), and exclusive breastfeeding before discharge (33% [5 of 15], 68% [89 of 131], 81% [87 of 107], p=0·0010). Average clinical practice scores rose from five of 42 (12%) to 16 of 42 (38%) and 24 of 42 (57%). Practice improvements were supported by updated clinical guidelines, hospital policies, and routines, by reorganisation of work, and by the provision of simple supplies, including gowns for mothers and caps for newborn babies. INTERPRETATION: The EENC clinical coaching approach coupled with regular self-assessments and action by hospital teams has significantly improved care practices during delivery and in the early post-partum period. It is possible that periodic cross-sectional practice reviews were not representative of routine practices, which may have varied with time of day, case load, and case complexity. Limitations were mitigated by assessing a systematic random sample of post-partum women delivering throughout the previous 24 h, and by measuring practices in two different time periods in each phase of implementation. Post-partum interviews were used to limit the Hawthorne effect. No other maternal or newborn initiatives were introduced during the study period, and no additional staff training was available, therefore the EENC approach was the primary influence on health worker practices. FUNDING: Support for this work was provided by WHO, occupied Palestinian territory.

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.

Redistribution of garbage codes to underlying causes of death: a systematic analysis on Italy and a comparison with most populous Western European countries based on the Global Burden of Disease Study 2019.

BACKGROUND: The proportion of reported causes of death (CoDs) that are not underlying causes can be relevant even in high-income countries and seriously affect health planning. The Global Burden of Disease (GBD) study identifies these 'garbage codes' (GCs) and redistributes them to underlying causes using evidence-based algorithms. Planners relying on vital registration data will find discrepancies with GBD estimates. We analyse these discrepancies, through the analysis of GCs and their redistribution. METHODS: We explored the case of Italy, at national and regional level, and compared it to nine other Western European countries with similar population sizes. We analysed differences between official data and GBD 2019 estimates, for the period 1990-2017 for which we had vital registration data for most select countries. RESULTS: In Italy, in 2017, 33 000 deaths were attributed to unspecified type of stroke and 15 000 to unspecified type of diabetes, these making a fourth of the overall garbage. Significant heterogeneity exists on the overall proportion of GCs, type (unspecified or impossible underlying causes), and size of specific GCs among regions in Italy, and among the select countries. We found no pattern between level of garbage and relevance of specific GCs. Even locations performing below average show interesting lower levels for certain GCs if compared to better performing countries. CONCLUSIONS: This systematic analysis suggests the heterogeneity in GC levels and causes, paired with a more detailed analysis of local practices, strengths and weaknesses, could be a positive element in a strategy for the reduction of GCs in Italy.

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.

Impact of Methylmercury and Other Heavy Metals Exposure on Neurocognitive Function in Children Aged 7 Years: Study Protocol of the Follow-up.

BACKGROUND: The extent to which prenatal low-level mercury (Hg) exposure through maternal fish intake and heavy metals exposure affect children's neurodevelopment is controversial and may appear in the long term. In 2007, a prospective cohort, the Northern Adriatic Cohort II (NAC-II), was established to investigate the association between prenatal Hg exposure from maternal fish consumption and child neurodevelopment. The study enrolled 900 pregnant women, and 632 and 470 children underwent neurodevelopmental evaluation at 18 and 40 months of age, respectively. The NAC-II cohort is a part of the Mediterranean cohort in the "Public health impact of long-term, low-level, mixed element exposure in susceptible population strata" project. METHODS: This protocol describes the follow-up assessment of the effects of prenatal low level Hg and other heavy metals exposure on the developing nervous system of the children born within the NAC-II who reached the age of 7 years. Child diet components are estimated through a Diet Diary. Child hair and urine are collected for determination of Hg level. In addition, levels of other potentially neurotoxic metals, namely Manganese, Cadmium, Lead, Arsenic, and Selenium, are also measured in the same matrices. DISCUSSION: This protocol extends to the first years of schooling age the evaluation of the neurotoxicant effect of Mercury and of the other heavy metals on children's neurodevelopment, adjusting for the potential confounders, such as the lifestyles and social economic status of children's families. Longitudinal analysis of neurodevelopment, assessed in different ages (18 months, 40 months, and 7 years), are performed.

Distraction Using Buzzy or Handheld Computers During Venipuncture.

OBJECTIVES: Venipuncture is one of the most frequently performed painful procedures in children. The aim of this study was to investigate the effectiveness of 2 analgesic strategies for venipuncture in children in a specific setting like a blood-drawing center. METHODS: This was a prospective randomized controlled trial. It was conducted in the blood-drawing center of a tertiary level children's hospital in Italy, between November 2014 and February 2015. Eligible patients were children aged from 4 to 12 years referred to the blood-drawing center for venipuncture. Enrolled children were randomized to be distracted by Buzzy device or by playing with a handheld computer. The procedural pain was measured with the faces pain scale-revised by children aged from 4 to 7 years and with a numerical rating scale by children aged from 8 to 12 years. RESULTS: Two hundred children with a median age of 8 years were enrolled in the study. The self-reported procedural pain was not statistically different between the Buzzy group and the handheld computer group: median (interquartile range) = 3.0 (1.0-4.8) and 2.0 (1.0-4.8), respectively (P = 0.72). Children reported significant pain in 25% of cases with both distraction strategies. The procedural success rate at the first attempt was not significantly different in the 2 groups. CONCLUSIONS: Analgesia provided by Buzzy or by a handheld computer was not significantly different in children undergoing venipuncture in a blood-drawing center, with the great proportion of them reporting no or mild pain during procedure.

[Disability in children and adolescents: a reflection of the Italian GBD initiative]. / La disabilità nei bambini e negli adolescenti: una riflessione dell'Italian GBD Initiative.

Childhood and adolescence are vulnerable and crucial phases for determining health in adulthood. Despite the enormous progress achieved in child and adolescent's health and well-being globally, the disability burden has remained almost unchanged. In 2019, in Italy and globally, low back pain, headache disorders, depression, and anxiety were among the first causes of disability. Through the analysis of the estimates of the Global Burden of Disease Study 2019, we propose a reflection on the state of health of the Italian paediatric and adolescent population in terms of disability, suggesting recommendations on preventive actions, and public health interventions. The aim is the improvement of their health, considering how the current COVID-19 pandemic is impacting on their quality of life.

Retrospective study 2005-2015 of all cases of fetal death occurred at ≥23 gestational weeks, in Friuli Venezia Giulia, Italy.

BACKGROUND: Intrauterine fetal death (IUFD) is a tragic event and, despite efforts to reduce rates, its incidence remains difficult to reduce. The objective of the present study was to examine the etiological factors that contribute to the main causes and conditions associated with IUFD, over an 11-year period in a region of North-East Italy (Friuli Venezia Giulia) for which reliable data in available. METHODS: Retrospective analysis of all 278 IUFD cases occurred between 2005 and 2015 in pregnancies with gestational age ≥ 23 weeks. RESULTS: The incidence of IUFD was 2.8‰ live births. Of these, 30% were small for gestational age (SGA), with immigrant women being significantly over-represented. The share of SGA reached 35% in cases in which a maternal of fetal pathological condition was present, and dropped to 28% in the absence of associated pathology. In 78 pregnancies (28%) no pathology was recorded that could justify IUFD. Of all IUFDs, 11% occurred during labor, and 72% occurred at a gestational age above 30 weeks. CONCLUSION: The percentage of IUFD cases for which no possible cause can be identified is quite high. Only the adoption of evidence-based diagnostic protocols, with integrated immunologic, genetic and pathologic examinations, can help reduce this diagnostic gap, contributing to the prevention of future IUFDs.

Pain Intensity and Risk of Bone Fracture in Children With Minor Extremity Injuries.

OBJECTIVES: Injuries are one of the most common causes of pediatric emergency department (ED) visit. The aim of this study was to investigate the relationship between the intensity of pain at the ED visit of children presenting with an extremity injury and the risk of fracture. METHODS: We conducted a retrospective study, considering all patients presenting to the ED of a children's hospital in Italy, with an accidental extremity injury, between May and December 2015. We selected all children aged 8 to 17 years who underwent an x-ray. Children with major, multiple, or nonextremity injuries were excluded. Age, sex, spontaneous and palpation pain, local swelling, time between injury, and medical evaluation were recorded. Sensibility and specificity of spontaneous and palpation pain in detecting a fracture were calculated. RESULTS: We reviewed 994 medical records; of these, 344 (34.6%) reported a fracture. Children's median age was 12 years (interquartile range [IQR], 10-14). Median spontaneous pain at the ED visit was not significantly different between children with and without a fracture: 4.0 (1.0-6.0) and 5 (1.0-6.0), respectively (P = 0.129). Children with mild palpation pain and children without an increase of pain of at least 2 points between spontaneous and palpation pain were fractured in 3.2% and 0.97% of cases, respectively. CONCLUSIONS: In this series, pain intensity in children with a minor extremity injury was not a good marker of fracture. Nevertheless, children with mild palpation pain or with a mild increase of pain between spontaneous and palpation pain had a low risk of fracture.

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.

Changing Epidemiology of Liver Involvement in Children With Celiac Disease.

OBJECTIVES: Available data indicate that liver involvement is present in a significant proportion of children with celiac disease (CD) at the diagnosis (elevated transaminases 15%-57%, autoimmune liver disease 1%-2%). We sought to evaluate prevalence, clinical course, and risk factors for liver involvement in a large cohort of children with CD. METHODS: Children (age 0-18 years) diagnosed with CD from March 2010 to April 2016 were enrolled. Liver involvement was considered to be present when alanine transaminase (ALT) levels were >40 U/L (hypertransaminasemia [HTS]). Patients with HTS were re-evaluated after at least 12 months of a gluten-free diet. RESULTS: CD was diagnosed in 806 patients during the study period; of these, ALT levels were available for 700 patients (86.9%), and were elevated in 27 (3.9%, HTS group); median ALT and aspartate transaminase levels in the HTS group were 57 U/L (interquartile range 49-80 U/L) and 67 U/L (interquartile range 53-85 U/L), respectively. Younger age, malabsorption symptoms, and low hemoglobin or ferritin were significantly more common in the HTS group at univariate analysis. At multivariate analysis, only age ≤4.27 years correlated with risk of liver involvement (odds ratio 3.73; 95% confidence interval: 1.61-8.66). When retested on a gluten-free diet, all but 3 patients normalized ALT levels; of these, 1 was diagnosed with sclerosing cholangitis. CONCLUSIONS: Liver involvement in celiac children is now less frequent than previously reported, possibly due to changing CD epidemiology. Younger age is the only risk factor. Associated autoimmune liver disease is rare.

Urinary metabolites of organophosphate and pyrethroid pesticides in children from an Italian cohort (PHIME, Trieste).

Urinary metabolites of organophosphate (OP) and pyrethroid (PYR) pesticides from seven years old children of a birth cohort study (n=199; PHIME cohort of Trieste, Italy) have been measured. Six OP and two PYR metabolites have been investigated, 2-diethylamino-6-methylpyrimidin-4-ol (DEAMPY, pirimiphos metabolite) was the one found at higher concentrations, median 3.4 ng/mL specific gravity adjusted (SG adjusted), followed by 4-nitrophenol (PNP, median 1.4 ng/mL SG adjusted) and 3,5,6-trichloro-2-pyridinol (TCPY, median 0.36 ng/mL SG adjusted), parathion and chlorpyriphos metabolites, respectively. TCPY concentrations were low in comparison to other distributions of OP metabolites in children from other studies. Accordingly, the PHIME cohort showed a distinct OP metabolite distribution with high concentrations of pirimiphos and parathion. Another specific characteristic of this cohort was the high concentration of 3-phenoxybenzoic acid (3-BPA, median 0.36 ng/mL SG adjusted), a general metabolite of PYR pesticides. Evaluation of anthropometric and socio-demographic characteristics of children and families only showed a positive association between family educational level and urinary concentrations of DEAMPY metabolite (p<0.05), which could reflect distinct dietary habits depending on the educational level. Estimated daily intakes were evaluated, all studied metabolites were found within safe levels.

Administering analgesia sublingually is a suitable option for children with acute abdominal pain in the emergency department.

AIM: Acute abdominal pain is a frequent complaint in children attending emergency departments. The aim of this study was to investigate the pain score reductions when children with acute abdominal pain received medication sublingually. METHODS: We carried out a multicentre randomised controlled trial in three children's hospitals in Italy between March 2015 and June 2017. Children from four to 18 years of age with acute abdominal pain were recruited if their self-reported pain was at least six on a scale from 0-10. The children were randomised to receive ketorolac 0.5 mg/kg (n = 70) or tramadol 2 mg/kg (n = 70) sublingually or a melt in the mouth powder of 20 mg/kg paracetamol (n = 70). The main study outcome was the pain scores for the three drugs after two hours. RESULTS: The 210 children (58.6% girls) had a median age of 12 years with an interquartile range of 9-14.3. The median pain scores at two hours were not significantly different between ketorolac 2.0 (interquartile ranges, IQR 0.0-4.3) and tramadol 3.0 (IQR 1.0-5.0) vs paracetamol 3.0 (IQR 0.8-5.0). The median pain reductions were all 5.0 points. CONCLUSION: Delivering analgesia sublingually was a suitable option for pain relief in children with acute abdominal pain in the emergency department.

Association of Gestational Weight Gain With Adverse Maternal and Infant Outcomes.

Importance: Both low and high gestational weight gain have been associated with adverse maternal and infant outcomes, but optimal gestational weight gain remains uncertain and not well defined for all prepregnancy weight ranges. Objectives: To examine the association of ranges of gestational weight gain with risk of adverse maternal and infant outcomes and estimate optimal gestational weight gain ranges across prepregnancy body mass index categories. Design, Setting, and Participants: Individual participant-level meta-analysis using data from 196 670 participants within 25 cohort studies from Europe and North America (main study sample). Optimal gestational weight gain ranges were estimated for each prepregnancy body mass index (BMI) category by selecting the range of gestational weight gain that was associated with lower risk for any adverse outcome. Individual participant-level data from 3505 participants within 4 separate hospital-based cohorts were used as a validation sample. Data were collected between 1989 and 2015. The final date of follow-up was December 2015. Exposures: Gestational weight gain. Main Outcomes and Measures: The main outcome termed any adverse outcome was defined as the presence of 1 or more of the following outcomes: preeclampsia, gestational hypertension, gestational diabetes, cesarean delivery, preterm birth, and small or large size for gestational age at birth. Results: Of the 196 670 women (median age, 30.0 years [quartile 1 and 3, 27.0 and 33.0 years] and 40 937 were white) included in the main sample, 7809 (4.0%) were categorized at baseline as underweight (BMI <18.5); 133 788 (68.0%), normal weight (BMI, 18.5-24.9); 38 828 (19.7%), overweight (BMI, 25.0-29.9); 11 992 (6.1%), obesity grade 1 (BMI, 30.0-34.9); 3284 (1.7%), obesity grade 2 (BMI, 35.0-39.9); and 969 (0.5%), obesity grade 3 (BMI, ≥40.0). Overall, any adverse outcome occurred in 37.2% (n = 73 161) of women, ranging from 34.7% (2706 of 7809) among women categorized as underweight to 61.1% (592 of 969) among women categorized as obesity grade 3. Optimal gestational weight gain ranges were 14.0 kg to less than 16.0 kg for women categorized as underweight; 10.0 kg to less than 18.0 kg for normal weight; 2.0 kg to less than 16.0 kg for overweight; 2.0 kg to less than 6.0 kg for obesity grade 1; weight loss or gain of 0 kg to less than 4.0 kg for obesity grade 2; and weight gain of 0 kg to less than 6.0 kg for obesity grade 3. These gestational weight gain ranges were associated with low to moderate discrimination between those with and those without adverse outcomes (range for area under the receiver operating characteristic curve, 0.55-0.76). Results for discriminative performance in the validation sample were similar to the corresponding results in the main study sample (range for area under the receiver operating characteristic curve, 0.51-0.79). Conclusions and Relevance: In this meta-analysis of pooled individual participant data from 25 cohort studies, the risk for adverse maternal and infant outcomes varied by gestational weight gain and across the range of prepregnancy weights. The estimates of optimal gestational weight gain may inform prenatal counseling; however, the optimal gestational weight gain ranges had limited predictive value for the outcomes assessed.

Multicenter randomized, double-blind controlled trial to evaluate the efficacy of laser therapy for the treatment of severe oral mucositis induced by chemotherapy in children: laMPO RCT.

OBJECTIVES: To demonstrate the efficacy of laser photobiomodulation (PBM) compared to that of placebo on severe oral mucositis (OM) in pediatric oncology patients. The primary objective was the reduction of OM grade (World Health Organization [WHO] scale) 7 days after starting PBM. Secondary objectives were reduction of pain, analgesic consumption, and incidence of side effects. METHODS: One hundred and one children with WHO grade > 2 chemotherapy-induced OM were enrolled in eight Italian hospitals. Patients were randomized to either PBM or sham treatment for four consecutive days (days +1 to +4). On days +4, +7, and +11, OM grade, pain (following a 0-10 numeric pain rating scale, NRS) and need for analgesics were evaluated by an operator blinded to treatment. RESULTS: Fifty-one patients were allocated to the PBM group, and 50 were allocated to the sham group. In total, 93.7% of PBM patients and 72% of sham patients had OM grade < 3 WHO on day +7 (P = 0.01). A significant reduction of pain was registered on day +7 in the PBM versus sham group (NRS 1 [0-3] vs. 2.5 [1-5], P < 0.006). Reduced use of analgesics was reported in the PBM group, although it was not statistically significant. No significant adverse events attributable to treatment were recorded. CONCLUSIONS: PBM is a safe, feasible, and effective treatment for children affected by chemotherapy-induced OM, as it accelerates mucosal recovery and reduces pain.